Evaluation of in vitro mucoadhesiveness and texture profile analysis of doxycycline in situ hydrogels.

Delivery of active ingredients to the oral mucosa from topically applied formulations reduces side effects from systemic administration and enhances the treatment efficiency. The challenge however, is to maintain the formulation at the administration site due to rapid salivary flow and mechanical movements of the mouth. Therefore, addition of mucoadhesive polymers could aid in enhancing the formulation residence time by increasing the mucoadhesion capacity but this effect is negligible especially if low ratio of mucoadhesive polymers are added to the formulation. Different mucoadhesive polymers at 0.5% w/w (either single or combination of two polymers) were added to the hydrogels and tested for mucoadhesion capacity, tensile strengths, adhesiveness, cohesiveness, compressibility and hardness. 0.5% povidone showed significantly highest work of mucoadhesion, 0.5% Carbopol formulation showed least cohesiveness and 0.5% HPMC showed highest adhesiveness, but a formulation containing a combination of 0.25% HPMC and 0.25% povidone showed the ideal parameters among all the mucoadhesive polymers tested. The effect of increase in concentration of HPMC (0.5, 1, 1.5, 2%) showed linear relationship for work of mucoadhesion and tensile strengths whereas for TPA the values were non-linear. The drug release from the optimized polymer matrices was found to follow zero-order release profile and the mechanism was found to be super case-II transport relaxation release. The results of this study indicate the mucoadhesive polymers do not impact the tensile strengths (p =0.05), but the texture properties and work of mucoadhesion of the formulations can be significantly (p <0.05) altered by the choice of mucoadhesive component at 0.5%w/w, though not for all the polymers tested. The study provides scope to predict in vivo performance and helps optimize for localized delivery.

The Basic Erosive Wear Examination (BEWE) applied retrospectively to two studies.

OBJECTIVES: A scoring method for tooth erosion is needed to enable community-based assessments. The aim of this study was to evaluate the Basic Erosive Wear Examination (BEWE) scoring method, using data previously collected from two studies. MATERIALS AND METHODS: In a national survey of erosion in children and adolescents, a representative, 20 % nationwide sample of 2,251 children, aged 6, 12 and 15 years, was examined. Erosion, recorded for all surfaces of permanent teeth, was converted to a BEWE score. For a group of referred patients, erosion was scored for 351 patients and then converted to a BEWE score. RESULTS: From the national survey, no erosion was seen in permanent teeth of 6 years old, but was present in 12 years old (19.9 % boys, mean BEWE of 0.22; 11.0 % girls, mean BEWE of 0.079; p < 0.001). Among 15 years old, erosion was seen in 30.7 % of subjects (38.3 % boys, mean BEWE of 1.00; 22.7 % girls, mean BEWE of 0.42; p < 0.001). For the referred patients, the BEWE score was 9.4 for subjects with gastric reflux symptoms but 6.0 for those without symptoms (p < 0.001). CONCLUSIONS: The value of scoring with the BEWE methodology was clearly demonstrated, showing increasing severity of erosion between 12 and 15 years and gender differences in erosion severity. Intrinsic acid erosion clearly caused an increased BEWE score. CLINICAL RELEVANCE: The BEWE scoring methodology appears valuable for assessing erosion in populations.

Approximal Caries Detection by DIFOTI: In Vitro Comparison of Diagnostic Accuracy/Efficacy with Film and Digital Radiography.

The aim of the present study was to compare the diagnostic accuracy/efficacy of digital imaging fiber-optic transillumination (DIFOTI) with film and digital radiography, in detection of approximal caries lesions. One hundred and twelve approximal surfaces were scored for caries, using DIFOTI images film and digital radiographs. All three sets of images were examined twice by 8 observers, with a minimal interval of one week between examinations. Validation of histological sections served as a reference standard. Reproducibility, based on intra- and interobserver agreement, was similar for all three methods. At diagnostic threshold D1 (enamel and dentin caries), DIFOTI showed significantly higher sensitivity, but differences in specificity between methods were nonsignificant. Diagnostic accuracy in the form of area under the receiver operating characteristic curve (AUC) was significantly higher for DIFOTI. At diagnostic threshold D3 (dentin caries), the differences in sensitivity and AUC among methods were nonsignificant, but DIFOTI showed significantly lower specificity. Compared with the radiographs, DIFOTI showed closer agreement, expressed as weighted kappa values, with the reference standard. The results show that under in vitro conditions, the diagnostic accuracy of DIFOTI in detecting early approximal enamel lesions is greater than that of film and digital radiography, while the potential for detecting lesions in dentin is similar for all three methods.

A 6-year longitudinal study of caries in teenagers and the effect of "dropouts" on the findings.

OBJECTIVES: To investigate attrition of subjects in a longitudinal study of caries. DESIGN: A radiographic study of caries and caries-associated factors was carried out in subjects, initially aged 14 years, and followed-up for six years. Attrition of subjects occurred at the last stage of the study. SETTING: A nationwide survey of subjects living in fishing, rural farming, and urban communities in Iceland. SAMPLE AND METHODS: A sub-sample of the nationwide random sample comprising 150 subjects was investigated using bitewing radiographs and a structured questionnaire to determine caries-risk factors. Subjects were re-examined at 16 years and 20 years using the same methods. RESULTS: Mean caries increment from 14-16 years was 3.0 lesions (1.5 lesions/subject/year) but reduced to 2.6 lesions (0.7 lesions/subject/ year) by 20y. The proportion of subjects found to be caries-free at 14 years, 16 years and 20 years, was 29%, 17% and 10%, respectively. "Dropouts" from this study occurred mostly after 16 years. Analysis of subjects dropping out showed that they were least likely to be from the rural farming community but most likely from the fishing community. Those dropping out attended their dentist less frequently, had a higher consumption of carbonated drinks and a higher prevalence and incidence of caries by 16 years. CONCLUSIONS: Subjects with high-risk behaviours, or residents in a fishing community were more likely to drop out of the study. Recognised advantages of conducting longitudinal studies of caries may, therefore, be lost.

Gastric reflux is a significant causative factor of tooth erosion.

Dental erosion is caused by dietary or gastric acid. This study aimed to examine the location and severity of tooth erosion with respect to causative factors, and to determine whether the clinical pattern of erosion reflected the dominant etiological factor. The study involved 249 Icelandic individuals and included: a detailed medical history; clinical oral examination; salivary sampling, and analysis for flow rate, pH, and buffering capacity. Reflux was assessed in 91 individuals by gastroscopy, esophageal manometry, and 24-hour esophageal-pH monitoring. Reflux symptoms were reported by 36.5% individuals. Manometry results were abnormal in 8% of study participants, abnormal esophageal pH in 17.7%, and a pathological 24-hour pH recording in 21.3%. 3.6% were positive for Helicobacter pylori. Normal salivary flow was found in 92%, but low salivary buffering (10.4%) was associated with erosion into dentin (P < 0.05). Significant associations were found between erosion and diagnosed reflux disease (OR 2.772; P < 0.005) and daily consumption of acidic drinks (OR 2.232; P < 0.005).

Longitudinal study of TP53 mutations in eight patients with potentially malignant oral mucosal disorders.

OBJECTIVES: In a previous cross-sectional study, the authors found a higher rate of TP53 mutation in oral lichen planus (OLP) than in hyperkeratosis. By analysing for TP53 mutations in serial samples from patients on long-term follow-up of their oral lesions, it was hoped to determine if these mutations were related to disease progression. METHODS: Eight patients presenting with lesions diagnosed clinically as oral leukoplakia or lichen planus were followed from 2 to 12 years. Two to five samples of archival biopsy tissue were analysed from each patient by constant denaturant gradient gel electrophoresis for hotspots A, B, C, D and exon 6. RESULTS: Four patients were diagnosed clinically as OLP: two of these were confirmed histopathologically, one was diagnosed as non-specific hyperkeratosis and one as cancer. Four patients had leukoplakia only, with a histopathological diagnosis of hyperkeratosis. Seven patients had TP53 mutations, three of them on repeated occasions. All five patients who developed squamous-cell carcinoma had mutations. Two of them had mutated pre-malignant lesions, and one of these previously had a non-mutated cancer. Three patients had two different primary cancers, only one of them mutated. One patient developed a mutated cancer 5 years after the last mutation-free biopsy. Of the cancer-free patients, a lesion regarded clinically as cancer-suspicious in one case was mutated, in another patient two OLP lesions were mutated, the third had five biopsies taken during 8 years, all non-mutated. CONCLUSIONS: TP53 mutations may occur early or late in the development of oral squamous-cell carcinoma.

Role of TP53 in the progression of pre-malignant and malignant oral mucosal lesions. A follow-up study of 144 patients.

BACKGROUND: Prediction of progression from pre-malignant oral mucosal lesions to malignancy, or recurrence of an existing oral squamous cell carcinoma (OSCC), is an important clinical problem in oral medicine. METHODS: This study presents a follow-up of a study published in 2002. Samples from 54 patients with OSCC, 45 with oral lichen planus (OLP) and 45 with hyperkeratosis (clinically leukoplakia), diagnosed between 1987 and 1996, were analysed for TP53 protein expression and TP53 mutation. Follow-up was 11-17 years for OSCC (mean 13.3), 12-22 years for OLP (mean 15.9) and 12-17 years for hyperkeratosis (mean 14.5). RESULTS: Of the 54 OSCC patients, 28 experienced recurrent disease, 21 died of OSCC, 22 died of other causes. Of the 14 OSCC patients with mutated TP53 (n = 11), the cancer recurred in eight (57%) and in 20/39 (51%) without mutation. Expression of TP53 protein was significantly associated with reduced overall survival. Among OLP patients, nine were TP53-mutated out of 31 tested. One TP53-mutated OLP patient developed OSCC in a different site. Of the hyperkeratosis patients, three were mutated of 22 tested. One hyperkeratosis patient (non-mutated) developed OSCC in the same site. CONCLUSION: TP53 mutations can exist in benign oral mucosal lesions for many years without progression to malignancy. No association was found between TP53 protein expression or TP53 mutation and recurrence of OSCC or disease-related survival. Overall survival was reduced in patients with positive TP53 protein expression.

Balancing the role of the dental school in teaching, research and patient care; including care for underserved areas.

Inequalities within dentistry are common and are reflected in wide differences in the levels of oral health and the standard of care available both within and between countries and communities. Furthermore there are patients, particularly those with special treatment needs, who do not have the same access to dental services as the general public. The dental school should aim to recruit students from varied backgrounds into all areas covered by the oral healthcare team and to train students to treat the full spectrum of patients including those with special needs. It is essential, however, that the dental student achieves a high standard of clinical competence and this cannot be gained by treating only those patients with low expectations for care. Balancing these aspects of clinical education is difficult. Research is an important stimulus to better teaching and better clinical care. It is recognized that dental school staff should be active in research, teaching, clinical work and frequently administration. Maintaining a balance between the commitments to clinical care, teaching and research while also taking account of underserved areas in each of these categories is a difficult challenge but one that has to be met to a high degree in a successful, modern dental school.

Enamel opacities in 8-year-old Icelandic children in relation to their medical history as infants.

OBJECTIVES: Opacities in tooth enamel were found in 34% of 8-year-old Icelandic children in 1970. This study aimed to measure the current prevalence of non-fluorotic enamel opacities in the maxillary incisors and to determine if their occurrence was related to significant events in the medical history. DESIGN: The prevalence of demarcated enamel opacities was recorded photographically by calibrated examiners. SETTING: Subjects lived in Reykjavík, Iceland. SAMPLE AND METHODS: A random sample of 290 children aged eight years was examined in 1997-8. Parents were asked if the child had a history of (i) colic as an infant and/or (ii) repeated middle-ear infection. RESULTS: Demarcated white enamel lesions, not resembling fluorosis, were seen in 41% of children (teeth photographed wet) rising to 51% (teeth photographed dry). Enamel hypoplasia was seen in 11% of wet teeth and 15% of dry teeth. Parents of 94/288 children (32.6%) reported that their child had infant colic and 52/94 (55.3%) had received medication. Three episodes or more of middle-ear infections per year were reported for 123/290 (42.4%) children. Significant association was seen between the presence of demarcated enamel opacities and a history of otitis media. Diffuse enamel opacities, assumed to be fluorosis, were not associated with events reported from the medical history. CONCLUSIONS: Non-fluoride opacities of teeth are still prevalent in Icelandic children especially those with a history of infections in infancy. Without a careful diagnosis these opacities might be confused with fluorosis.

Profile and competences for the European dentist.

This paper presents the profile and competences for the European Dentist as approved by the General Assembly of the Association for Dental Education in Europe at its annual meeting held in Cardiff in September 2004. A task-force drafted the document, which was then sent to all European Dental Schools. Reactions received were used to amend the document. European dental schools are expected to adhere to the profile and the 17 major competences but the supporting competences may vary in detail between schools. The document will be reviewed in 5 years time. This paper will be disseminated to ministries of health, national dental associations and dental specialty associations or societies in Europe and these organisations will be asked to offer their comments. This information will be used in the reviewing process to be started in 2007. It is hoped that the availability of this document will assist dental schools in Europe to further harmonize and improve the quality of their curricula.

Clonal persistence of oral Fusobacterium nucleatum in infancy.

Once established, early-colonizing bacterial species tend to persist in the mouth. To obtain detailed information on the population dynamics of early-colonizing oral anaerobes, we examined the clonal diversity and persistence of clones among oral Fusobacterium nucleatum populations during the first 2 yrs of life. Consecutive salivary samples from 12 infants, collected at 2, 6, 12, 18, and 24 mos of age, yielded a total of 546 F. nucleatum isolates for clonal typing with arbitrarily primed PCR (AP-PCR). Up to 7 AP-PCR types were simultaneously detected in each sample. In 11 out of the 12 infants examined, AP-PCR types persisted for up to 1 yr. Strain turnover rate was high during the first year of life, but then the occurrence of persistent clones increased. This study indicates a wide genetic diversity within the species and provides evidence for the increasing persistence of F. nucleatum clones in the oral cavity with age.

Relationship between dental erosion, soft drink consumption, and gastroesophageal reflux among Icelanders.

The aim of this study was to determine the prevalence of dental erosion in young Icelandic adults (19-22 years old) and patients with gastroesophageal reflux disease (GERD), in relation to their soft drink consumption and gastroesophageal reflux. Eighty subjects (40 males and 40 females), comprising 57 young adults (mean age 21 +/- 2 years) and 23 GERD patients (mean age 35 +/- 10 years), were enrolled in this study. All subjects answered a detailed frequency questionnaire of soft drink consumption and participated in a clinical examination. Erosion was scored for incisor and molar teeth separately. No significant difference was observed in the prevalence of dental erosion between young adults and GERD patients. However, by combining the two study groups a three-fold higher risk of having erosion in molars or incisors was found for subjects drinking Coca-Cola three times a week or more often ( p < 0.05). Additionally, significantly higher erosion scores were found in molars among subjects drinking more than 1 litre of carbonated drinks (all brands) per week ( p < 0.05). It is concluded that the frequency of soft drink consumption is a strong risk factor in the development of dental erosion.

Herpetic gingivostomatitis in otherwise healthy adolescents and young adults.

The purpose of this study was to review and analyze the records of herpes simplex infections from a specialist Oral Medicine clinic in Iceland, to investigate the clinical impression that the age of patients experiencing initial infection with this virus was higher than expected and that the character of the clinical picture of the disease had changed. Records of patients with herpes infections attending the Oral Medicine clinic covering a 3-year period were examined and the clinical and virological data analyzed. Diagnosis was based on clinical appearance, history, and viral identification with culture or detection of viral DNA by means of the polymerase chain reaction. Records of 60 patients (34 female) were included in the study (mean age, 23.1 years; range, 2 68 years). No patients were known or suspected to be positive for human immunodeficiency virus, none was known to be immunocompromised, and 38 patients (mean age, 16.6 years; 21 female) were diagnosed as having primary herpetic gingivostomatitis. Eighteen patients (mean age, 36.2 years; 11 female) had lesions of recurrent herpes simplex infection present on the oral mucosa. Primary infection with herpes simplex virus was more common in young adults than had been expected. Recurrent infections appeared on the oral mucosal even in otherwise healthy patients, and the clinical course of these infections in this age group sometimes followed a more severe course than that seen in young children.

Identifying clinically important gram-negative anaerobes from the oral cavity.

Gram-negative oral anaerobes have frequently been associated with periodontal disease, some species more frequently than others. The confusing classification of these organisms has often obscured the association with disease of particular species within this group of organisms. This investigation aimed to compare different identification methods that could be applied in clinical research. Clinical isolates were collected and identified by three different methods: screening with phenotypic tests, commercial identification kits, and a 16S rRNA-based polymerase chain reaction (PCR) method. Forty-three reference strains of 19 Prevotella and Porphyromonas species were also included in the investigation. The phenotypic screen easily differentiated Porph. gingivalis from the other pigmented species. The screen also gave a good indication of separation of the lactose-fermenting species from the lactose non-fermenting species, although diversity can be seen in beta-galactosidase activity. Commercial identification kits did not add much to identification achieved with the phenotypic screen, only 20% of Porph. gingivalis isolates could be identified to species level with the kits. Neither the kits nor the phenotypic screen could differentiate Pr. intermedia and Pr. nigrescens. With the PCR method, Pr. intermedia and Pr. nigrescens were easily separated, and Porph. gingivalis was readily identified. Because of 16S rRNA gene sequence similarity, Pr. melaninogenica and Pr. veroralis could not be separated by the PCR method.

Aqueous hydrocortisone mouthwash solution: clinical evaluation.

Patients often experience difficulties in applying topical steroids in orabase to the oral mucosa, particularly when large areas need to be covered. An aqueous hydrocortisone mouthwash solution has been developed, one that was anticipated to be more acceptable to patients. The solution contains hydrocortisone (0.3% w/v) in a 4.5% (w/v) 2-hydroxypropyl-beta-cyclodextrin solution. Hydroxypropylmethylcellulose (0.5% w/v) was used to increase the viscosity of the solution and to promote the hydrocortisonecyclodextrin complex. One hundred and two patients with aphthous ulceration, lichen planus, and other mucosal conditions used the mouthwash in an open clinical efficacy study. Most patients reported some or considerable improvement following a 2-week course of treatment with the mouthwash: 26 of 33 (78.8%) patients with aphthous ulceration were 'much better', as were 26 of 54 (48.1%) patients with lichen planus and 5 of 16 (31.3%) patients with other mucosal lesions. No serious side effects were reported. Aqueous mouthwash solutions offer a potential vehicle for topical steroid therapy of oral mucosal lesions.

Approximal caries and sugar consumption in Icelandic teenagers.

The aim of this study, conducted in 1994, was to examine the association between approximal caries and sugar consumption in teenagers residing in three fluoride-deficient areas in Iceland while controlling for a number of behavioral, residential and microbiological factors. One hundred and fifty subjects (mean age 14 years) selected from the Icelandic Nutritional Survey (INS) were examined radiographically and they completed questionnaires about sugar consumption frequency. Total grams of sugar intake were obtained from the INS for each subject. Caries experience on approximal surfaces, diagnosed from radiographs, was used as the dependent variable in the analyses. Altogether 45.2% of subjects were caries free on approximal surfaces. The overall sample was found to have a mean DFS on approximal surfaces of 2.73 (s=4.36) per subject. Average daily total sugar intake was 170 g per subject and the mean number of sugar-eating occasions between meals was 5.32 (s=6.29) per subject. The regression model indicated that the frequency of between-meal sugar consumption was associated with approximal caries, with frequency of candy consumption being the most important of the sugar variables. In multivariate analysis, no relationship was found between dental caries and total daily intake of sugar, although a significant relationship between total sugar consumption and presence of caries was seen in bivariate analysis. Between-meal consumption of sugar remains a risk factor for the occurrence of dental caries, especially in populations with moderate-to-high levels of dental caries experience.

A hemagglutinating variant of Prevotella melaninogenica isolated from the oral cavity.

Strains resembling Prevotella melaninogenica were isolated from healthy subjects and patients with periodontal disease and were identified using: a 5-test phenotypic screen; commercial identification kits; and a 16S rRNA-based polymerase chain reaction (PCR) method. Eleven clinical isolates closely resembling P. melaninogenica, and all from patients with periodontitis, were able to agglutinate erythrocytes. In the electron microscope, hemagglutinating isolates showed fimbria-like structures, that were not seen on non-hemagglutinating isolates. Some strains were further classified with PCR-restriction fragment-length polymorphism (RFLP) of 16S rRNA genes. Amplified 16S rDNA was digested using five different endonucleases, separated with agarose gel electrophoresis, stained and photographed. Photographs were then scanned, digitized and a distance matrix calculated using Dice coefficient, where the presence or absence of a band was used as a character. The distance matrix was plotted as a phenogram. At 70% similarity six clusters were seen. Type strains of separate Prevotella species did not fall into any cluster. Hemagglutinating isolates fell into three clusters: four clustered with the type strains of P. melaninogenica and Prevotella veroralis; four with other P. melaninogenica isolates and two hemagglutinating isolates clustered together Prevotella loescheii. The PCR-RFLP results showed that the hemagglutinating strains did not form a homogenous group inside the Prevotella genus.

Trends in dental health among Icelandic urban children.

Caries experience, oral hygiene and caries-related salivary parameters were recorded in a 20% representative sample of 12-year-old schoolchildren in Reykjavik, Iceland in 1991. The majority of the children was re-examined 3 years later in 1994. Trends in prevalence of caries and salivary bacteria were assessed by comparison with an analogous earlier longitudinal study (1984-87). Mean DFS values for 12-year-olds were 12.1 and 4.1, for 15-year-olds 23.3 and 11.3 in the earlier and later study, respectively. Reduction in DFS was 66% and 52% for the respective age groups. The decline was most pronounced in the group with low caries prevalence. Trends in caries experience were paralleled by salivary bacteria. The mean caries scores and frequency distributions of 15-year-olds in 1994 closely resembled those of 12-year-olds a decade earlier, suggesting a delay rather than a true fall in caries prevalence.