Cortisol daily rhythm in saliva of healthy school children.

AIM: To investigate the daily rhythm of cortisol levels in saliva of school children. SUBJECTS AND METHODS: Probands (10-14 years, both genders) were recruited via personal contact and school visits. Exclusion criteria included hormonal and dental treatments during the trial, pharmaceuticals containing cortisol, or poor oral hygiene. Each volunteer collected 20 saliva samples during one day at defined times starting immediately after waking up and ending at night. Additionally, they completed a sampling diary. Saliva samples were analysed in duplicate using a commercial cortisol luminescence kit. RESULTS: Cortisol concentration in saliva followed a daily rhythm. Within 20 minutes after waking up cortisol reached the highest level of 9.69 (+/-3.89) nmol/L. After 90 minutes cortisol concentration decreased linearly by 50% and stagnated at 4.14 (+/-1.93) nmol/L for 3 to 8 hours. Thereafter, levels decreased gradually reaching almost zero after 14 hours. Overall, no gender-specific differences in saliva cortisol levels were observed except for 3 time points: 3, 10 and 11 hours after waking. CONCLUSION: This study establishes guidelines for a normal secretion pattern, plus explores pain level measurements and their correlation to saliva cortisol levels in this age group.

Conventionally ligated versus self-ligating metal brackets--a comparative study.

The purpose of this study was to compare the frictional properties of four self-ligating metal brackets, Speed, Damon 2, In-Ovation, and Time, with those of three conventionally ligated metal brackets, Time, Victory Twin, and Discovery. The self-ligating Time bracket can also be used as a conventionally ligated bracket. Friction was tested 20 times for each bracket/wire combination using a Zwick testing machine with stainless steel wires in three different wire dimensions (0.017 x 0.025, 0.018 x 0.025, and 0.019 x 0.025 inches). All brackets had a 0.022 inch slot and the prescription of an upper first premolar. The data were statistically analysed with unsigned comparisons of all bracket/wire combinations using the Mann-Whitney U-test and the Games-Howell post hoc test. The results showed almost all brackets to have the lowest frictional force with a wire dimension of 0.018 x 0.025 inch. Friction of the self-ligating brackets using wire with a dimension of 0.018 x 0.025 inches was 45-48 per cent lower than with 0.017 x 0.025 and 0.019 x 0.025 inch wires. Friction of the conventionally ligated brackets showed a 14 per cent or less reduced friction with 0.018 x 0.025 inch wire compared with 0.017 x 0.025 and 0.019 x 0.025 inch wires. The self-ligating metal brackets showed lower frictional forces with a 0.018 x 0.025 inch wire than conventionally ligated brackets, whereas conventionally ligated brackets showed lower friction with 0.017 x 0.025 and 0.019 x 0.025 inch wire. Friction values vary with different bracket/archwire combinations and, therefore, the choice of a bracket system for treatment should consider the correct wire dimension to produce the lowest possible frictional forces.

Frictional properties of aesthetic brackets.

The purpose of this study was to compare the frictional properties of two self-ligating aesthetic brackets, Opal (Ultradent Products) and Oyster (Gestenco Int.), with those of four conventionally ligated aesthetic brackets, Transcend (3M Unitek), Inspire (Ormco), Allure (GAC Int.), and Image (Gestenco Int.). Friction was tested with different wire dimensions and qualities [stainless steel (SS) wire 0.017 x 0.025 inches; SS 0.019 x 0.025 inches; TMA 0.019 x 0.025 inches] using a Zwick testing machine. All brackets had a 0.022-inch slot and the prescription of an upper first premolar of the Roth system (tip: 0 degrees, torque: -7 degree). Each bracket/archwire combination was tested 10 times and each test was performed with a new bracket/wire sample that was pulled through twice. Additionally, two sets of 30 Opal brackets each were aged with an ageing machine under standardized conditions for 9-10 and 18-20 months, respectively. Friction of the aged brackets was tested with identical wire dimensions and qualities using the same testing procedure. All data were statistically analysed with unsigned comparisons of all bracket/wire combinations using GLM and the Games-Howell post hoc test. The results showed Opal brackets to have the lowest frictional forces for all wire dimensions and qualities. Furthermore, friction was lower at a significant level (P

[Cleidocranial dysplasia. Description and analysis of a patient cohort]. / Dysostosis cleidocranialis. Beschreibung und Analyse einer Patientengruppe.

BACKGROUND: Cleidocranial dysplasia (CCD) is a rare dysplasia of bony and dental tissue. Characteristic are typical craniofacial and dental findings including morphological anomalies. CCD is possibly the only general syndrome that can be diagnosed based on the dental findings alone. CCD correlates with mutations in the RUNX2 gene. PURPOSE: The present interdisciplinary study correlates phenotypic findings with genetic variations in the corresponding gene. PATIENTS AND METHODS: The coding sequence of the RUNX2 gene from 31 CCD patients from 20 families was analyzed using molecular genetic methods including polymerase chain reaction and direct sequencing. The craniofacial and dental findings of each patient were evaluated according to a standardized scoring scheme and tested with homogeneity analysis for general phenotypic findings. RESULTS: Several mutations of the RUNX2 gene were identified. Depending on the mutation type, they showed different distribution patterns within the gene coinciding with the functional domains of the gene product. With homogeneity analysis of the phenotype cardinal (especially dental findings) and minor findings (pneumatization disturbances, Wormian bones) were identified. In combination with the genetic data, the statistical analysis showed that loss-of-function mutations of the RUNX2 gene result in a milder markedness of the CCD phenotype than gain-of-function or decrease-of-function mutations. CONCLUSIONS: We found that type and location of a specific mutation within the RUNX2 gene might have an impact on the expressivity of CCD. Due to the limited sampling size this hypothesis must be verified by investigations in larger patient groups.

[Anomalies of the skull in cleidocranial dysplasia]. / Schädelanomalien bei Dysostosis cleidocranialis. Eine HNO-ärztliche und kraniofaziale Röntgenstudie.

BACKGROUND: The description of the otorhinolaryngeal and craniofacial anomalies in patients with cleidocranial dysplasia. METHODS: For this study, 26 patients with cleidocranial dysplasia were examined after their medical history had been recorded. The main focus was placed on otorhinolaryngological and orthodontic findings. RESULTS: The portion of spontaneous mutations in our patient population was 46.1%. All patients exhibited otorhinolaryngological and craniofacial anomalies. While single ENT-anomalies were expressed in 76.9%-92.3% of the patients, the craniofacial findings were distributed over 84.6%-92.3%. CONCLUSION: The expression of this rare disorder is variable and its symptomatology not always distinct. Otorhinolaryngological and craniofacial anomalies are often apparent. Appropriate treatment can significantly contribute to an improvement in the patient's quality of life. In cases of ambiguous findings, we recommend consultation with an experienced clinician as well as genetic counselling.

Pressure simulation of orthodontic force in osteoblasts: a pilot study.

OBJECTIVES: To elucidate the RUNX2 gene expression induction in human osteoblasts after mechanical loading. DESIGN: Using a stringent pulse-chase protocol human osteoblasts were exposed to centrifugal pressure force for 30 and 90 min. Untreated control cells were processed in parallel. Before, and at defined times after centrifugation, total RNA was isolated. RUNX2 gene expression was measured using real-time quantitative reverse transcriptase polymerase chain reaction. The stress/control ratio was used to illustrate possible stimulatory or diminishing effects of force application. RESULTS: Immediately after 30 min of force application the RUNX2 gene expression was induced by a factor of 1.7 +/- 0.14 as compared with the negative control. This induction decreased rapidly and reached its pre-load levels within 30 min. Longer force applications (up to 90 min) did not change the RUNX2 gene expression. CONCLUSION: In mature osteoblasts centrifugal pressure force stimulates RUNX2 gene expression within a narrow time frame: loading of mature cells results in a temporary increase of RUNX2 expression and a fast downregulation back to its pre-load expression level. With this pilot study the gene expression behavior after mechanical stimuli could be determined with a simple laboratory setup.

Early craniofacial signs of cleidocranial dysplasia.

OBJECTIVES: Early diagnosis of CCD is essential for a timely introduction of the appropriate treatment approach. Since certain symptoms first fully manifest only during the pubertal growth spurt, their indicatory signs are often overlooked. The aim of this study is to describe the initial craniofacial findings in patients with CCD in order to categorise their reliability for early detection. METHOD: 14 patients with CCD between the ages of 6 and 11 years who were referred to the University of Regensburg over a 4-year period were included in this study. The patients were examined clinically and radiologically and their dental status was determined. Typical signs of CCD were analysed according to such classic criteria as the 'quatermoon'-physiognomy described in the literature. The clinical findings were compared to medical data and case history. RESULTS: Early signs were registered for each patient. While some signs could be found in all patients, others were variably expressed. The typical extraoral symptoms were only rarely exhibited in our patient population. CONCLUSION: As various indicators of CCD are age related, their expression should be taken into account for early diagnosis. Apparent signs only manifest during the growth spurt when the ideal timeframe for beginning treatment has already past. The symptoms described should serve as early markers to aid the general and paediatric dentist in planning appropriate treatment or referring patients to specialised centres.

[Symptoms and signs in cleidocranial dysplasia (CCD)]. / Symptome und Merkmale bei Dysostosis Cleidocranialis (DCC).

AIM: Occurrence of main symptoms and the rate of spontaneous mutations in patients with cleidocranial dysplasia. METHOD: 24 patients with variable phenotypic expression of CCD were examined symptomatically. The main focus was placed on findings in the shoulder girdle, craniofacial symptoms and alterations in radiologic opacity. RESULTS: The average age of the patients was 18.3 years. In our patient cohort, 58.3% were spontaneous mutations. Abnormal apposition of the shoulders were found in 88% of the patients. Craniofacial symptoms were diagnosed in 88%. An increase of the radiologic skull density was apparent in 95%. CONCLUSION: The expression of this rare disorder is variable and its symptomatology not always apparent. Spontaneous mutations occur frequently. Due to the high prevalence of the considered symptoms, the diagnosing physician should focus on the facial appearance and shoulder abnormalities. In cases of ambiguous findings we recommend a consultation of an experienced clinician as well as genetic counseling.

Dentomaxillofacial variability of cleidocranial dysplasia: clinicoradiological presentation and systematic review.

OBJECTIVES: The aim of this study was to determine the clinical and radiological presentation of cleidocranial dysplasia (CCD) in our patient group and to compare them with other reported cases by a systematic review (SR) of the literature. METHODS: The study comprises two elements, a complete series of all diagnosed patients at the Center for Craniofacial Genetics at the University of Regensburg, Germany, and a SR. Relevant literature was identified by electronic databases, review of citation lists and hand searching of key journals. The principal selection criterion was that the study should contain as many pertinent cases as possible. The presented signs and symptoms were assigned to the following categories: "supernumerary teeth", "failure of eruption", "hypoplastic maxilla" and "clavicular sign". Additionally, the family history was taken into account. RESULTS: From the 410 English, German or French articles, 40 single case presentations and 17 multiple case studies remained that met the selection criteria. This report reviews the data of 283 patients with CCD including our own patient cohort of 24 individuals. Dental signs such as supernumerary teeth and eruption failure were expressed in over 93.5%. Skeletal symptoms such as hypoplastic maxilla and the clavicular sign were exhibited in over 84.3%. The prevalence of spontaneous mutations differs slightly when comparing the single case studies (72.0%) with our patient data (58.3%). The fraction of spontaneous mutations in multiple case studies was 5.0%. CONCLUSION: The diagnosis of CCD can be difficult when typical features are not clearly expressed. Since the multiple case studies concentrated on specific clinical aspects, an overall ranking including all associated findings was not possible. Owing to their prevalence, we recommend referencing to the described list of clinical signs as major symptoms for the pathognomy in CCD, since they are infrequent in other conditions and in the general population. To categorize the expression of CCD, more interdisciplinary studies are necessary. Nevertheless, a subjective classification is possible according to the related restrictions in the patients' quality of life.

[Inter- and intrafamilial expression of cleidocranial dysostosis]. / L'expressivité inter- et intrafamiliale de la dysostose cléido-crânienne.

Cleidocranial dysplasia is a bony autosomal dominant disorder, defined by late closure of fontanels and sutures, clavicular aplasia or hypoplasia and supernumerary teeth. The aim of our study was to define the CBFA1 mutations in three families with cleidocranial dysplasia and to describe the phenotype expression within and between the families. While the mutation R225Q caused a similar phenotype within one family, the mutation G146R, located in the same domain, was the cause of a variable expression between two family members. A third mutation, R190Q was responsible for symptoms not commonly associated with this disorder. The results of our craniofacial examination are in agreement with the numerous descriptions in the literature. This study accents the difficulty in establishing a clinical based diagnosis due to the wide variability.

Atypical expression of cleidocranial dysplasia: clinical and molecular-genetic analysis.

Cleidocranial dysplasia (CCD) and the Rubinstein-Taybi syndrome (RTS) are two rare congenital syndromes that have many clinical signs in common. We present an 18-year-old-patient with untypical CCD expression who was misdiagnosed with RTS at the age of 2 years. An extensive craniofacial examination was carried out with respect to morphological and dental aspects. The molecular-genetic analysis of two underlying genes (CBFA1 and CBP) for CCD and RTS was performed using SSCP, direct sequencing and FISH. While the clinical examination showed uncharacteristic CCD symptoms with some findings common for RTS, the molecular-genetic analysis revealed a missense mutation in the CBFA1 gene, which is considered to be the etiological factor for CCD. Our findings with this patient presented clear evidence for the wide morphologic variety that can be related to a certain gene such as CBFA1. The diagnosis of rare diseases is currently based on the clinical phenomenology of small groups or single cases. The use of molecular-genetic biology extends the horizon of diagnostic and scientific possibilities. In this patient, it allowed us to compare the clinically diagnosis to molecular-genetic data. We conclude that molecular-genetic analysis may be a helpful tool in the differential diagnosis of many congenital diseases such as CCD and RTS.

A novel missense mutation of the CBFA1 gene in a family with cleidocranial dysplasia (CCD) and variable expressivity.

The aim of this study was to analyze the CBFA1 gene in a phenotypically variable family with autosomal dominant cleidocranial dysplasia (CCD). Five members of a family with CCD were characterized clinically. X-rays and photographs of the two clinically affected family members were taken. The genotype of all five affected family members was determined with the use of single strand conformation polymorphism (SSCP) and direct sequencing. A point-mutation in exon 2 (R148G) was detected in a patient with the full-blown clinical phenotype. His son, demonstrating the same mutation, showed only the dental CCD characteristics. No mutation could be found in the three clinically healthy family members. To conclude, a missense mutation in the CBFA1 gene was detected in a family with variably expressed CCD syndrome. A detailed clinical examination is necessary to detect minimally affected gene mutation carriers.