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Oral clefts play an essential role in disturbed odontogenesis of the deciduous and permanent dentition, yet little is known about this relationship. We investigated, within the categories cleft lip with or without alveolus (CL ± A) and cleft lip, alveolus and palate (CLAP), whether different CL subphenotypes based on morphological severity of the cleft show different dentition patterns and whether a more detailed subdivision of the incomplete CL has clinical relevance. In this retrospective study, 345 children with nonsyndromic unilateral CL ± A and CLAP from the Dutch Association for Cleft Palate and Craniofacial Anomalies (NVSCA) registry were included to assess the association between the CL subphenotypes and lateral incisor patterns. Five different deciduous and permanent patterns of the lateral incisor were distinguished: located in normal position (pattern z/Z), in the anterior segment (pattern x/X) or in the posterior segment of the cleft (pattern y/Y), one in each segment of the cleft (pattern xy/XY), and agenesis of the lateral incisor (pattern ab/AB). Analyses were performed by using multinomial logistic regression models. Children born with a vermillion notch or a one-third to two-thirds CL were most likely to have a deciduous pattern x and a permanent pattern X, while children born with a two-thirds to subtotal CL were most likely to have deciduous pattern xy and a permanent pattern X compared to children with a complete CL that predominantly had deciduous pattern y and a permanent pattern AB. Based on the relationship of the CL morphology with the deciduous dentition, subdivision of the CL morphology into vermillion notch to two-thirds CL, two-thirds to subtotal CL, and complete CL appears to be an optimal subdivision. Our results indicate that a more detailed subdivision of the CL has clinical relevance and that critical factors in the pathogenesis of the CL are also critical for the odontogenesis.

Introduction: The aim of our study was to evaluate the craniofacial characteristics of children with mild hypodontia using conventional and principal component (PC) analysis., Methods: We used radiographic images of 124 children (8-12 years old) with up to 4 missing teeth (55 boys, 69 girls) and of 676 reference children (365 boys, 311 girls) from the Rotterdam Generation R Study and the Nijmegen Growth Study in The Netherlands. Fifteen cephalometric measurements of children with hypodontia were compared with those of the reference children. Moreover, cephalometric parameters were combined into standardized PC scores using PC analysis, and the components were compared between the 2 groups., Results: PC analysis showed common dental characteristics for all types of hypodontia: a significant increase of the interincisal angle, and decreases of the maxillary and mandibular incisor angles. Other findings were consistent when both methods were applied: (1) anterior hypodontia was significantly associated with the high-angle (hyperdivergent) craniofacial pattern, (2) the tendency toward a Class III malocclusion was identified in maxillary hypodontia, and (3) we observed a significant reduction of lower posterior facial height in children with posterior and mandibular hypodontia., Conclusions: Our findings suggest that children with mild hypodontia have distinctive skeletal and dental features., (Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Objectives: In this cross-sectional study, we aimed to investigate the pattern of hypodontia in the Dutch population and determine the association between hypodontia and dental development in children with and without hypodontia, applying three different standards, Dutch, French Canadian, and Belgian, to estimate dental age., Methods: We used dental panoramic radiographs (DPRs) of 1488 children (773 boys and 715 girls), with a mean age of 9.76 years (SD = 0.24) participating in a population-based cohort study in Rotterdam, the Netherlands, born in 2002-2004, and 452 children (219 boys and 233 girls) with a mean age of 9.83 years (SD = 1.09) participating in a mixed-longitudinal, interdisciplinary population-based cohort study in Nijmegen, the Netherlands born in 1960-1968., Results: The prevalence of hypodontia in the Generation R Study was 5.6 % (N = 84) and 5.1 % (N = 23) in the Nijmegen Growth Study. Linear regression analysis showed that children with hypodontia had a 0.37 [95 % CI (-0.53,-0.21)] to 0.52 [95 % CI (-0.76,-0.38)] years lower dental age than children without hypodontia. The ordinal regression analysis showed a delay in development of mandibular second premolars [1.68 years; 95 %CI (-1.90,-1.46)], mandibular first premolars [0.57 years; 95 % CI (-0.94,-0.20)], and mandibular second molars [0.47 years; 95 % CI (-0.84,-0.11)]., Conclusion: These findings suggest that children with hypodontia have a delayed dental development., Clinical Relevance: The delay of dental development in children with hypodontia should be taken into consideration and therefore orthodontists should recognize that a later start of treatment in these patients may be necessary.

Background: The EUROCRAN index has been used in inter-center studies to assess dental arch relationship (DAR) and palatal morphology (PM) in children with unilateral cleft lip and palate (UCLP). For this type of inter-center research, a scoring method that could be performed over the internet would be the most effective. Therefore, the aim of this study was to investigate the reliability of application of the EUROCRAN index on 3D digital models or photographs of plaster models instead of using plaster models., Methods: The EUROCRAN reference models were presented in three formats: plaster models, 2D photographs of plaster models, and 3D digital models. Plaster models of children with UCLP (n = 45) were rated. Of each case, all three formats were rated by six calibrated observers in random order. The strength of agreement of the ratings was assessed with kappa statistics. Concordance among observers was evaluated with the intra-class correlation coefficient (ICC)., Results: The ICC showed a good inter-observer agreement for the DAR and poor inter-observer agreement for the PM. Intra-observer agreement for the DAR was moderate to very good, yet for the PM poor to moderate. Comparison between the three formats per observer for the DAR was good or very good and for the PM moderate to poor., Conclusions: The overall results show that the EUROCRAN index is an acceptable and reliable scoring method for the DAR on plaster models, 2D photographs of plaster models, and 3D digital models. However, due to the small range of deviations in palatal morphology between the cases in our study, the PM component of the index was difficult to assess., Clinical Relevance: In clinical audits and inter-center studies, plaster models can be substituted by 2D photographs of plaster casts or 3D digital models when grading treatment outcome with the EUROCRAN index.

Background/objective: Judgement of nasolabial aesthetics in cleft lip and palate (CLP) is a vital component of assessment of treatment outcome. It is usually performed based on two-dimensional (2D) facial photographs. An increasing use of three-dimensional (3D) imaging warrants an assessment if 3D images can substitute 2D photographs during aesthetic evaluation. The aim of this study was to compare reliability of rating nasolabial appearance on 3D images and standard 2D photographs in prepubertal children., Methods: Forty subjects (age: 8.8-12) with unilateral CLP treated according to a standardized protocol, who had 2D and 3D facial images were selected. Eight lay raters assessed nasal form, nasal deviation, vermilion border, and nasolabial profile on cropped 2D and 3D images using a 100-mm visual analogue scale (VAS). Additionally, raters answer two questions: 1. Do 2D or 3D images provide more information on nasolabial aesthetics? and 2. Is aesthetic evaluation easier on 2D or 3D images?, Results: Intrarater agreement demonstrated a better reliability of ratings performed on 3D images than 2D images (correlation coefficients for 3D images ranged from 0.733 to 0.857; for 2D images from 0.151 to 0.611). The mean scores showed, however, no difference between 2D and 3D formats (>0.05). 3D images were regarded more informative than 2D images (P = 0.001) but probably more difficult to evaluate (P = 0.06)., Limitations: Basal view of the nose was not assessed., Conclusions: 3D images seem better than 2D images for rating nasolabial aesthetics but raters should familiarize themselves with them prior to rating., (© The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Assess facial asymmetry in subjects with unilateral cleft lip (UCL), unilateral cleft lip and alveolus (UCLA), and unilateral cleft lip, alveolus, and palate (UCLP), and to evaluate which area of the face is most asymmetrical., Methods: Standardized three-dimensional facial images of 58 patients (9 UCL, 21 UCLA, and 28 UCLP; age range: 8.6-12.3 years) and 121 controls (age range 9-12 years) were mirrored and distance maps were created. Absolute mean asymmetry values were calculated for the whole face, cheek, nose, lips, and chin. One-way analysis of variance, Kruskal-Wallis, and t-test were used to assess the differences between clefts and controls for the whole face and separate areas., Results: Clefts and controls differ significantly for the whole face as well as in all areas. Asymmetry is distributed differently over the face for all groups. In UCLA, the nose was significantly more asymmetric compared with chin and cheek (P = 0.038 and 0.024, respectively). For UCL, significant differences in asymmetry between nose and chin and chin and cheek were present (P = 0.038 and 0.046, respectively). In the control group, the chin was the most asymmetric area compared to lip and nose (P = 0.002 and P = 0.001, respectively) followed by the nose (P = 0.004). In UCLP, the nose, followed by the lips, was the most asymmetric area compared to chin, cheek (P < 0.001 and P = 0.016, respectively)., Limitations: Despite division into regional areas, the method may still exclude or underrate smaller local areas in the face, which are better visualized in a facial colour coded distance map than quantified by distance numbers. The UCL subsample is small., Conclusion: Each type of cleft has its own distinct asymmetry pattern. Children with unilateral clefts show more facial asymmetry than children without clefts., (© The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To determine the relationship between nasolabial symmetry and esthetics in subjects with orofacial clefts., Material and Methods: Eighty-four subjects (mean age 10 years, standard deviation 1.5) with various types of nonsyndromic clefts were included: 11 had unilateral cleft lip (UCL); 30 had unilateral cleft lip and alveolus (UCLA); and 43 had unilateral cleft lip, alveolus, and palate (UCLAP). A 3D stereophotogrammetric image of the face was taken for each subject. Symmetry and esthetics were evaluated on cropped 3D facial images. The degree of asymmetry of the nasolabial area was calculated based on all 3D data points using a surface registration algorithm. Esthetic ratings of various elements of nasal morphology were performed by eight lay raters on a 100 mm visual analog scale. Statistical analysis included ANOVA tests and regression models., Results: Nasolabial asymmetry increased with growing severity of the cleft (p = 0.029). Overall, nasolabial appearance was affected by nasolabial asymmetry; subjects with more nasolabial asymmetry were judged as having a less esthetically pleasing nasolabial area (p < 0.001). However, the relationship between nasolabial symmetry and esthetics was relatively weak in subjects with UCLAP, in whom only vermilion border esthetics was associated with asymmetry., Conclusions: Nasolabial symmetry assessed with 3D facial imaging can be used as an objective measure of treatment outcome in subjects with less severe cleft deformity. In subjects with more severe cleft types, other factors may play a decisive role., Clinical Significance: Assessment of nasolabial symmetry is a useful measure of treatment success in less severe cleft types.

In patients with agenesis or enamel anomalies in anterior teeth combined orthodontic and restorative treatment is often necessary to achieve an optimal aesthetic result. How both can best be achieved, but also how to maintain the result, requires communication between the dentist and the orthodontist. The orthodontic treatment plan needs to be established in cooperation with the dentist who will carry out the restorative treatment while the patient is at a young age. Since with these young patients, who are still growing craniofacially and whose teeth are still developing, possible future restorative and/or orthodontic treatment, as well as the means of orthodontic retention, need to be included in the treatment plan. In cleft palate patients, it is also important that methods of orthodontic retention of maxillary arch width are given timely attention in the restorative treatment plan because it is especially vulnerable to relapse.

The aim of this study was to analyse changes in the volume of the chin after harvest of a bone graft for secondary reconstruction of an alveolar cleft. Cone-beam computed tomographic (CT) scans of 27 patients taken preoperatively, and immediately and one year postoperatively, were analysed, and 3-dimensional hard-tissue reconstructions made. The hard-tissue segmentation of the scan taken one year postoperatively was subtracted from the segmentation of the preoperative scan to calculate the alteration in the volume of bone at the donor site (chin). A centrally-orientated persistent concavity at the buccal side of the chin was found (mean (range) 160 (0-500) mm(3)). At the lingual side of the chin, a central concavity remained (mean (range) volume 20 (0-80) mm(3)). Remarkably, at the periphery of this concavity there was overgrowth of new bone (mean (range) volume 350 (0-1600) mm(3)). Re-attachment of the muscles of the tongue resulted in a significantly larger central lingual defect one year postoperatively (p=0.01). We also measured minor alterations in volume of the chin at one year. Whether these alterations influence facial appearance and long term bony quality is to be the subject of further research., (Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Many studies have established dental age standards for different populations; however, very few studies have investigated whether dental development is stable over time on a population level. Therefore, the aim of this study was to analyze changes in dental maturity in Dutch children born between 1961 and 2004. We used 2,655 dental panoramic radiographs of 2- to 16-year-old Dutch children from studies performed in three major cities in the Netherlands. Based on a trend in children born between 1961 and 1994, we predicted that a child of a certain age and gender born in 1963 achieved the same dental maturity on average, 1.5 years later than a child of the same age born 40 years later. After adjusting for the birth year of a child in the analysis, the regression coefficient of the city variable was reduced by 56.6% and it remained statistically significant. The observed trend from 1961 to 1994 was extrapolated to 9- to 10-year-old children born in 2002-2004, and validation with the other samples of children with the same characteristics showed that 95.9%-96.8% of the children had dental maturity within the 95% of the predicted range. Dental maturity score was significantly and positively associated with the year of birth, gender, and age in Dutch children, indicating a trend in earlier dental development during the observation period, 1961-2004. These findings highlight the necessity of taking the year of birth into account when assessing dental development within a population with a wider time span., (Copyright © 2014 Wiley Periodicals, Inc.)

The physiology of masseter muscles is known to change in response to functional demands, but the effect on the satellite cell (SC) population is not known. In this study, the hypothesis is tested that a decreased functional demand of the masseter muscle causes a reduction of SCs. To this end, twelve 5-week-old male Sprague-Dawley rats were put on a soft diet (SD, n = 6) or a hard diet (HD, n = 6) and sacrificed after 14 days. Paraffin sections of the superficial masseter and the m. digastricus (control muscle) were stained with haematoxylin and eosin for tissue survey and with anti-myosin heavy chain (MHC) for slow and fast fibres. Frozen sections of both muscles were double-stained for collagen type IV and Pax7. Slow MHC fibres were equally distributed in the m. digastricus but only localized in a small area of the m. masseter. No differences between HD or SD for the m. digastricus were found. The m. masseter had more SCs per fibre in HD than in SD (0.093 ± 0.007 and 0.081 ± 0.008, respectively; P = 0.027). The m. masseter had more fibres per surface area than the m. digastricus in rats with an SD group (758.1 ± 101.6 and 568.4 ± 85.6, P = 0.047) and a HD group (737.7 ± 32.6 and 592.2 ± 82.2; P = 0.007). The m. digastricus had more SCs per fibre than the m. masseter in the SD group (0.094 ± 0.01 and 0.081 ± 0.008; P = 0.039). These results suggest that reduced masseter muscle function is related to a lower number of SCs. Reduced muscle function might decrease microdamage and hence the requirement of SCs in the muscle fibres.

Background: Current guidelines for evaluating cleft palate treatments are mostly based on two-dimensional (2D) evaluation, but three-dimensional (3D) imaging methods to assess treatment outcome are steadily rising., Objective: To identify 3D imaging methods for quantitative assessment of soft tissue and skeletal morphology in patients with cleft lip and palate., Data Sources: Literature was searched using PubMed (1948-2012), EMBASE (1980-2012), Scopus (2004-2012), Web of Science (1945-2012), and the Cochrane Library. The last search was performed September 30, 2012. Reference lists were hand searched for potentially eligible studies. There was no language restriction., Study Selection: We included publications using 3D imaging techniques to assess facial soft tissue or skeletal morphology in patients older than 5 years with a cleft lip with/or without cleft palate. We reviewed studies involving the facial region when at least 10 subjects in the sample size had at least one cleft type. Only primary publications were included., Data Extraction: Independent extraction of data and quality assessments were performed by two observers., Results: Five hundred full text publications were retrieved, 144 met the inclusion criteria, with 63 high quality studies. There were differences in study designs, topics studied, patient characteristics, and success measurements; therefore, only a systematic review could be conducted. Main 3D-techniques that are used in cleft lip and palate patients are CT, CBCT, MRI, stereophotogrammetry, and laser surface scanning. These techniques are mainly used for soft tissue analysis, evaluation of bone grafting, and changes in the craniofacial skeleton. Digital dental casts are used to evaluate treatment and changes over time., Conclusion: Available evidence implies that 3D imaging methods can be used for documentation of CLP patients. No data are available yet showing that 3D methods are more informative than conventional 2D methods. Further research is warranted to elucidate it.

Primary failure of eruption is a rare eruption disorder of above all, the permanent second and sometimes the first molars. It is characterized by infra occlusion of the molars resulting in a severe lateral open bite. Primary failure of eruption is a disorders which affects all molars distal to the most mesial involved tooth. Diagnosis is possible both clinically and with radiographs. A panoramic radiograph combined with clinical findings of impaction or infra occlusion can confirm the suspicion of primary failure of eruption. Primary failure of eruption cannot be treated as other eruption disturbances are. The teeth do not respond to orthodontic force. Exposure of the molar and orthodontic traction of a molar affected by primary failure of eruption is discouraged. Observation and extraction, in case the primary failure of eruption poses a risk to the healthy dentition, are the only two treatment options for young patients. Additional treatment of this eruption disorder should be carried out at an adult age and consists of prosthetic closure of the open bite.

Patients with cleft left lip and palate (CLP) normally require extensive surgery from an early age up to the end of adolescence. These surgeries affect the growth of the maxillofacial complex. The degree to which the cleft itself affects growth of the maxillofacial complex remains poorly understood. By analysing the width and elevation of the palatal shelves in unoperated adolescents and adults with unilateral and bilateral cleft lip and palate (UCLP and BCLP, respectively) and a non-cleft control group, it is possible to gain more insight into the real intrinsic growth potential of the maxillary structures. In this study, dental casts of the full permanent dentition of individuals with unrepaired UCLP (n = 68) and BCLP (n = 13) and non-cleft controls (n = 24) from the same area of Indonesia were digitized three-dimensionally. Maxillary arch width in the canine, premolar and molar regions, and the width and elevation of the palatal shelves were measured. Results showed that in patients with UCLP, the width of the palatal shelves on the cleft side in all regions, and on the non-cleft side in the canine/first premolar region, was significantly smaller compared with the control group. BCLP subjects showed similar deviations. In the UCLP group, the palatal shelves were rotated cranially and positioned more vertically. In the BCLP group, the palatal shelves were inclined by almost 10 ° more than the control group. The width of the palatal shelf and width of the maxillary arch positively correlated in the canine and first premolar regions for both the cleft and non-cleft side in patients with UCLP, and in the canine region for patients with BCLP. This means that the wider the palatal shelf, the wider the maxillary arch. The elevation of palatal shelves correlated with the maxillary arch width in all regions in patients with UCLP, and only in the premolar region in the control group. Thus, the wider the arch width, the smaller the elevation angle (the maxillary shelves are less vertical). No correlations between palatal shelf elevation and maxillary arch width were found in the BCLP group. This shows that the intrinsic growth potential in patients with UCLP and BCLP is affected by a smaller palatal shelf width and larger elevation of the shelves. These deviations may result in a wider cleft., (© 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.)

Background: The authors conducted a systematic review of cone-beam computed tomography (CBCT) applications in orthodontics and evaluated the level of evidence to determine whether the use of CBCT is justified in orthodontics., Types of Studies Reviewed: The authors identified articles by searching the Cochrane Library, PubMed, MEDLINE, Embase, Scopus and Cumulative Index to Nursing and Allied Health Literature databases. They searched the articles' reference lists manually for additional articles and had no language limitations. They did not search the gray literature. Inclusion criteria were CBCT use in orthodontics and that the participants be human. The lowest level of evidence accepted for inclusion was a case series with five or more participants. The authors evaluated the studies' methodological quality according to 13 criteria related to study design, measurements and statistical analysis., Results: The authors identified 550 articles, and 50 met the inclusion criteria. Study topics included temporary anchorage devices, cephalometry, combined orthodontic and surgical treatment, airway measurements, root resorption and tooth impactions, and cleft lip and palate. The methodological quality averaged 53 percent (range, 15-77 percent) of the maximum score., Clinical Implications: The authors found no high-quality evidence regarding the benefits of CBCT use in orthodontics. Limited evidence shows that CBCT offers better diagnostic potential, leads to better treatment planning or results in better treatment outcome than do conventional imaging modalities. Only the results of studies on airway diagnostics provided sound scientific data suggesting that CBCT use has added value. The additional radiation exposure should be weighed against possible benefits of CBCT, which have not been supported in the literature. In future studies, investigators should evaluate the effects of CBCT on treatment procedures, progression and outcome quantitatively.

The restoration of muscles in the soft palate of patients with cleft lip and/or palate is accompanied by fibrosis, which leads to speech and feeding problems. Treatment strategies that improve muscle regeneration have only been tested in limb muscles. Therefore, in the present study the myogenic potential of muscle progenitor cells (MPCs) isolated from head muscles was compared with that of limb muscles. Muscle progenitor cells were isolated from the head muscles and limb muscles of rats and cultured. The proliferation of MPCs was analysed by DNA quantification. The differentiation capacity was analysed by quantifying the numbers of fused cells, and by measuring the mRNA levels of differentiation markers. Muscle progenitor cells were stained to quantify the expression of paired box protein Pax 7 (Pax-7), myoblast determination protein 1 (MyoD), and myogenin. Proliferation was similar in the head MPCs and the limb MPCs. Differentiating head and limb MPCs showed a comparable number of fused cells and mRNA expression levels of myosin-1 (Myh1), myosin-3 (Myh3), and myosin-4 (Myh4). During proliferation and differentiation, the number of Pax-7(+), MyoD(+), and myogenin(+) cells in head and limb MPCs was equal. It was concluded that head and limb MPCs show similar myogenic capacities in vitro. Therefore, in vivo myogenic differences between those muscles might rely on the local microenvironment. Thus, regenerative strategies for limb muscles might also be used for head muscles., (© 2012 Eur J Oral Sci.)

Background: The authors conducted a literature review to assess whether there is a reduction of salivation with the use of antisialogogues, whether the use of antisialogogues reduces the chair time needed for dental procedures and whether the use of antisialogogues reduces bond failure in orthodontics., Methods: The authors conducted a search for original articles published from 1950 to April 2010 by using the following databases: Cochrane Collaboration, PubMed, Scopus, EMBASE and ISI Web of Knowledge. They included in their review only human studies in which antisialogogues were used. They validated methodological quality and evidence grade., Results: Twenty-six studies met the inclusion criteria. Twenty-five of these studies were related to the effect of antisialogogues on salivation, and one study to bond failure. The authors found that there is evidence that antisialogogues work, inconclusive evidence that they reduce bond failure, and no evidence that they reduce chair time for dental procedures., Clinical Implications: Taking into account the systemic effects of antisialogogues, which exceed the time needed for bracket bonding, the use of antisialogogues for dental procedures in general is questionable.

Objectives: To study maxillary arch width in adult patients with bilateral cleft lip and alveolus (BCLA) or with complete bilateral cleft lip and palate (BCLP), who have not had any surgery. SETTING AND SAMPLING POPULATION: Eighteen patients with BCLA, 13 patients with BCLP, and 24 controls from remote areas of Indonesia collected over 10 years., Materials and Methods: Dental casts were digitized three-dimensionally using an industrial coordinate measuring machine (CCM) (Zeiss Numerex; Carl Zeiss, Stuttgart, Germany). Transversal distance between molars was measured on the tip of the distobuccal cusp and the tip of the mesiobuccal cusp, and for premolars and canines, the tip of the buccal cusps was recorded. Means and standard deviations were calculated for all variables. t-Test was used to determine whether the mean values of the cleft groups showed significant differences from each other and from the controls. Level of significance was set at p < 0.05., Results: Transversal arch dimensions in the BCLA group were comparable to the controls except at the canine level. Intercanine distance, which is close to the alveolar cleft, was 4.3 mm (SE 1.4) smaller in the BCLA group (p = 0.002). In the BCLP group, a comparable pattern was found. At the canine level, mean transversal width was 7.2 mm (SE 1.9) smaller compared to the control group, but no significant differences were found in the other transversal dimensions., Conclusions: Small differences are found in transversal dimensions in patients with BCLA and BCLP compared to a control group. Differences are most outspoken in the area near the cleft.

Objectives: To study occlusal wear of anterior teeth in orthodontic patients retained with different retainers until 5 years post-treatment, and to investigate whether type of retention influences occlusal wear., Material and Methods: Orthodontic patients (n=222), aged 15 years maximally at the start of treatment, were followed until 5 years post-treatment. In the maxilla, a retainer bonded on all six teeth or a removable retainer was used; in the mandible, a lingual retainer was bonded on all anterior teeth or on canines only. Dental casts were analyzed before treatment (T(0)), after treatment (T(1)), and 5 years post-treatment (T(5)). Incisal and canine wear were scored by applying a grading scale. Intercanine width, overjet, and overbite were measured with an electronic caliper. Statistics used were: Paired samples t-test for differences over time; Pearson correlation coefficients for associations between wear and retention type; and backward linear regression for influence of retention type on wear., Results: There was an increase in wear during all time periods and for all teeth. From T(0) to T(5) an increase in maxillary intercanine width and maxillary retention had an effect on changes in canine wear. Incisal wear was associated with an increase in upper intercanine width (T(1)-T(5)). For both arches, an increase in maxillary intercanine width during treatment was associated with less progression of canine and incisal wear, but the explained variance was low, 13.4% and 19.3%, respectively., Conclusions: Retention type and, occasionally, an increase in intercanine width influence anterior teeth wear post-treatment. However, the clinical significance and impact of the examined retention methods on occlusal wear are small.

Aims: Underprescribing is increasingly recognized as an important problem. The aim of this study was to determine the relationship between polypharmacy and underprescribing., Methods: Treatment of current medical problems in geriatric patients was compared with general practitioner and national guidelines. Underprescription was defined as lack of an indicated drug, while no reason could be found for not prescribing it. Polypharmacy was defined as five or more drugs., Results: Polypharmacy was present in 61% of 150 patients. Underprescription was found in 47 (31%). Of patients with polypharmacy 42.9% were undertreated, in contrast to 13.5% of patients using four medicines or less (OR 4.8, 95% CI 2.0, 11.2). The estimated probability of underprescription increased significantly with the number of drugs., Conclusions: We found a clear relationship between polypharmacy and underprescribing.

With regard to the optimal treatment timing for children with an Angle Class II division 1 malocclusion, there is an ongoing controversy on the effectiveness of a two-phase or a one-phase therapy. Two-phase treatment involves a first phase to correct the jaw relationship starting at the age of 7 to 9 years, and, when all permanent teeth are present, a second phase of treatment by fixed appliances. A one-phase treatment involves treatment of the jaw relationship and the dental malocclusion simultaneously or consecutively, starting during the early adolescence period. In recent years, several randomized controlled clinical trials have been performed on this topic. More recently, a Cochrane meta-analysis of these trials has been published. The results show that early treatment of an Angle Class II division 1 malocclusion followed by a second phase of treatment does not have any advantages over treatment that is started later and finished in one phase. One-phase treatment is as effective as two-phase treatment, while the time needed for treatment is shorter and, as a consequence, total costs are lower. Dentists should take into account this information, when treating children with an Angle Class II division 1 malocclusion or referring them to an orthodontist.

Objective: To examine the accuracy and precision of the Steiner prediction cephalometric analysis., Setting and Subjects: The sample consisted of 275 randomly selected patients, treated between 1970 and 1995 at a university department., Methods: Lateral cephalograms before (T1) and after orthodontic treatment (T2) were analyzed using the Steiner analysis. A prediction of the final outcome at T2 for the variables ANB degrees, U1 to NA mm, L1 to NB mm, and Pg to NB mm was performed at T1. The difference between the actual outcome at T2 and the Steiner predicted value (SPV), which was done at T1, was calculated. Accuracy (mean difference between T2 and SPV) and precision (standard deviation of the mean prediction discrepancies) of the prediction were studied. Paired t-test was used to detect under- or overestimation of the predicted values., Results: The mean decrease in angle ANB was 1.4 +/- 2.7 degrees and for U1 to NA 2.0 +/- 2.6 mm, while L1 to NB increased 0.8 +/- 2.0 mm and Pg to NB 0.7 +/- 1.1 mm. The predicted values for the changes in ANB angle, the distance of upper incisor U1 to NA as well as the distance Pg to NB were significantly overestimated when compared with the actual outcome, while the change in the distance of lower incisor L1 to NB was underestimated., Conclusion: The prediction of cephalometric treatment outcome as used in the Steiner analysis is not accurate enough to base orthodontic treatment decisions upon.

Single tooth replacement with a dental implant is an increasingly popular solution in patients with loss of an upper anterior tooth. There is a risk, however, of placing the implant prematurely in youths. In a case series the effects of residual maxillary growth on the results of implant treatment in the anterior maxillary region were measured. The results confirm findings from other studies on this subject and indicate that cessation and degree of vertical growth are unpredictable. This may result in infraposition of the implant and lead to periodontal bone loss around the implant region and its neighbouring teeth. Clinicians should be aware of this and inform their patients that these changes may eventually compromise the aesthetic result of the treatment.

Telomeres, nucleoprotein complexes at chromosome ends, protect chromosomes against end-to-end fusion. Previous in vitro studies in human fibroblast models indicated that telomere dysfunction results in chromosome instability. Loss of telomere function can result either from critical shortening of telomeric DNA or from loss of distinct telomere-capping proteins. It is less clear whether telomere dysfunction has an important role in human cancer development in vivo. Acute myeloid leukemia (AML) is a good model to study mechanisms that generate chromosome instability in human cancer development because distinct groups of AML are characterized either by aberrations that theoretically could result from telomere dysfunction (terminal deletions, gains/losses of chromosome parts, nonreciprocal translocations), or aberrations that are unlikely to result from telomere dysfunction (e.g., reciprocal translocations or inversions). Here we demonstrate that AML with multiple chromosome aberrations that theoretically could result from telomere dysfunction is invariably characterized by critically short telomeres. Short telomeres in this group are not associated with low telomerase activity or decreased expression of essential telomeric capping proteins TRF2 and POT1. In contrast, telomerase activity levels are significantly higher in AML with short telomeres. Notably, short telomeres in the presence of high telomerase may relate to significantly higher expression of TRF1, a negative regulator of telomere length. Our observations suggest that, consistent with previous in vitro fibroblast models, age-related critical telomere shortening may have a role in generating chromosome instability in human AML development.

Approximately one third of the Dutch population has an objective need for orthodontic treatment. Yet, patients mostly seek treatment because of aesthetic reasons. Recent social developments and the increased attention for aesthetics ask for ways to objectively measure treatment need. This is not only important because of the risks of orthodontic treatment, but also because of financial reasons. In this article indices to verify treatment need, i.e. the Index for Orthodontic Treatment Need (IOTN), de Dental Aesthetic Index (DAI) en de Index of Complexity, Outcome and Need (ICON), are discussed. All three indices seem to lead to a reduction of treatment need, especially in borderline cases. They can serve as 'neutral' instruments to discuss treatment need with patients and as instruments to allocate financial resources for orthodontic care.

The critical factors in the regulation of telomere length are not yet clearly defined. Telomerase is a key player in telomere elongation, although previous studies have shown that telomeres are differentially elongated after telomerase reconstitution. Moreover, a clear relation between the level of telomerase activity and telomere length was not observed. To investigate which factors are critical in telomere length regulation, we generated 24 telomerase-reconstituted primary human fibroblast clones. In these clones, in vitro telomerase activity level is clearly related to telomere length. High levels of telomerase activity are associated with longer telomeres and better telomere maintenance over time. The correlation coefficient, however, indicates that the level of telomerase activity is not the only factor in the regulation of telomere length. Clearly, factors that are not measured in an in vitro telomerase activity assay are involved in telomere length regulation in vivo. To investigate which telomerase components are critical in regulating telomerase activity levels, we studied expression levels of hTERT mRNA and hTR. Expression is highly variable between individual clones, but not related to the level of telomerase activity or telomere length. Our results indicate that expression levels of hTERT mRNA and hTR do not regulate the activity level of the telomerase complex, suggesting posttranscriptional modification of hTERT or the presence of additional proteins that modulate telomerase enzyme activity.

In experimental animals inhibition of T cell co-stimulation immediately after organ transplantation effectively prevents rejection. We investigated whether the expression of co-stimulatory molecules is enhanced in cadaveric liver transplants, whether their expression is influenced by the transplantation procedure, and whether variation in expression between liver transplants is related to the occurrence of acute rejection. Expression of CD80, CD86 and the macrophage marker CD68 were determined by immunohistochemistry in biopsies from 40 clinical liver transplants obtained at different time-points during the transplantation procedure, and in normal liver tissue obtained from 10 human livers. Expression of CD80 and CD86 on Kupffer cells was graded by comparison with CD68-staining. In a subgroup CD80 and CD86 mRNA was quantified by real-time detection polymerase chain reaction. CD86 was expressed in all liver transplants and normal livers on the majority of Kupffer cells. CD80 was absent or sporadically expressed in normal liver tissue, but in 18 of 40 liver transplants at least one-quarter of Kupffer cells expressed CD80. CD80- and CD86-mRNA and protein expression in liver transplants did not change during the warm ischaemic and reperfusion phases of the transplantation procedure. CD80-expression on Kupffer cells varied strongly between individual donor livers; this variation was, however, not significantly related to the occurrence of acute rejection after transplantation. In conclusion, in nearly half of cold-preserved cadaveric liver transplants an increased proportion of Kupffer cells express CD80 at the time of transplantation in comparison with normal liver tissue. The expression was not further induced by warm ischaemia and reperfusion. However, the observed variation in CD80-expression between liver transplants is not a accurate predictive measure for acute rejection.

We investigated whether determination in fine-needle aspiration biopsy (FNAB) specimens of cells expressing granzymes (Grs) and Fas ligand would provide a reliable, easy, and quantitative measure of rejection activity in the transplanted liver. Retrospectively, 13 FNAB specimens obtained during clinical acute rejection, 10 FNAB specimens obtained during subclinical rejection, 12 FNAB specimens obtained during cytomegalovirus (CMV) infection, and 26 FNAB specimens obtained in the absence of rejection or infection were included on the study. Cytospin preparations of FNAB and peripheral-blood specimens were immunocytochemically stained for Fas-ligand and Gr, and increments in the liver were calculated by subtracting frequencies of positive cells in blood from those in FNAB specimens. Only sporadically Fas ligand-expressing, but many Gr-expressing, cells were detected in FNAB specimens. Increments in Gr-positive (Gr(+)) cells were significantly greater in FNAB specimens obtained during clinical rejection (median, 70 Gr(+) cells; range, 0 to 312 Gr(+) cells; P = .006) and tended to be greater in FNAB specimens obtained during subclinical rejection (median, 62 Gr(+) cells; range, 5 to 113 Gr(+) cells; P = .09) compared with those obtained in the absence of rejection (median, 16 Gr(+) cells; range, 0 to 103 Gr(+) cells). Increments obtained during clinical or subclinical rejection did not differ from those obtained during CMV infection (median, 27 Gr(+) cells; range, 6 to 212 Gr(+) cells). With the exclusion of specimens obtained during CMV infection, the sensitivity of Gr determination in FNAB specimens for the diagnosis of acute rejection (either clinical or subclinical) was 70%, and specificity, 69%. In FNAB specimens obtained during clinical and subclinical acute rejection episodes after liver transplantation, increased numbers of Gr-expressing cells were present; in the absence of CMV infection, their quantification provides a measure for rejection activity with moderate accuracy.