Ildikó Tarján

Safety and immunogenicity of a prepandemic influenza A (H5N1) vaccine in children.

Background: The avian influenza A (H5N1) virus is considered to be a potential cause of the next influenza pandemic. Children may be particularly vulnerable to the pandemic virus, and they may react differently than adults to vaccines. We report the results of the first clinical trial of an H5N1 vaccine in children. Methods: Twelve healthy children (mean age ± SD: 12.73 ± 2.77 years) received a single dose of 6 μg of the inactivated whole virus vaccine Fluval. Twenty-one days after vaccination, immunogenicity was assessed by hemagglutination inhibition and microneutralization assays. Safety information was collected for 180 days. Results: No side-effects were observed, and the vaccine fulfilled all applicable U.S. and European immunogenicity criteria for licensure. The post/prevaccination geometric mean titer ratio was 16.95, the rate of seroconversion was 75% and the rate of seroprotection was also 75% 21 days after vaccination. Conclusions: We confirmed our earlier findings of the present vaccine in adults showing encouraging safety and immunogenicity properties in children. Studies with the present vaccine in elderly subjects are underway.

Prevalence and distribution of permanent canine agenesis in dental paediatric and orthodontic patients in Hungary

Non-syndromic permanent canine agenesis, or combined with agenesis, or developmental absence of other tooth types, has occasionally been described in the literature, but isolated forms are rarely observed. The purpose of the present retrospective radiographic study was to provide data on the prevalence and distribution of permanent canine agenesis in the Hungarian population. Dental panoramic tomograms and the medical history data of 4417, 6- to 18-year-old children (average age 12 years, male-to-female ratio 1:1), who presented for treatment at the Department of Paediatric Dentistry and Orthodontics of the Semmelweis University Budapest, Hungary, were examined. Patients with systemic diseases were excluded. Chi-square and Fishers tests were performed to determine statistical significance at a level of P < 0.05. Thirteen subjects had permanent canine agenesis. The overall prevalence was 0.29 per cent. The prevalence of permanent canine agenesis was 0.27 per cent in the maxilla and 0.09 per cent in the mandible (P < 0.01). The male-to-female ratio was 1:2.2. Dental anomalies associated with permanent canine agenesis were found: 11 patients had retention of the primary canines, 10 other types of agenesis of the permanent teeth, one a primary supernumerary tooth, one a supernumerary cusp, and nine occlusal disturbances.

Facial and dental appearance of Williams syndrome

Williams syndrome is a genetic condition, which predominantly occurs as a sporadic disorder, although some families have been reported showing autosomal dominant inheritance with varying penetrance. The incidence of Williams syndrome is estimated to be one in 20 000–50 000 live births, and it consists of supravalvular aortic stenosis, characteristic dysmorphic facial features named “elfin face” (wide mouth with long phyltrum and …

Echocardiographic findings in patients with Williams-Beuren syndrome.

ZusammenfassungHINTERGRUND: Das Williams-Beuren-Syndrom (WBS) ist ein mehrere Organsystem betreffender Entwicklungsschaden, der durch eine Mikrodeletion am Chromosom 7q11.23 bedingt ist. In seiner klassischen Form präsentiert es sich mit dysmorphen Gesichtszügen, mit Gelenkskontrakturen, mit Wachstums-und mentaler Retardation, mit räumlichen und visuellen kognitiven Defiziten, Hyperkalzämie, sowie mit primärer und sekundärer Hypertonie und kardiovaskulären Erkrankungen. ZIEL: Die klinische Diagnose des WBS kann bei sehr jungen Patienten eine Herausforderung darstellen, wenn die charakteristischen kardiovaskulären Erkrankungen, wie z.B. die supravalvuläre Aortenstenose, oder die Pulmonalarterien-Stenose fehlen. Unser Ziel war es, die bekannten und auch die selteneren Veränderungen der kardiovaskulären Läsionen in der postnatalen Periode solcher Kinder mit WBS zu erfassen, sowie alle möglichen Veränderungen im kardiovaskulären Bereich, die in der Nachsorge dokumentiert wurden zu erheben. METHODEN: Es wurde der kardiovaskuläre Status bei 29 Kindern (mittleres Alter zum Untersuchungszeitpunkt: 12,8 Jahre) mit WBS erhoben und mit dem Alter korreliert. ERGEBNISSE: Bei der Mehrzahl der Patienten (72,4%) änderte sich die kardiovaskuläre Diagnose im Laufe der Zeit. Interessanterweise hatten 44,8% der Patienten Perioden ohne berichtete Erkrankungen im kardiovaskulären Bereich. Außerdem hatten 65,5% Perioden ohne die für das WBS typischen oben angeführten kardiovaskulären Erkrankungen. Es wurden spontane Rückgänge sowohl der supravalvulären Aortenstenose als auch der Pulmonalarterienstenosen beobachtet. Weiters wurde eine unerwartet hohe Prävalenz (41%) von Erkrankungen der Mitralklappe festgestellt. SCHLUSSFOLGERUNGEN: Unsere Studie zeigt, dass das vorübergehende Verschwinden der pathologischen Befunde im kardiovaskulären Bereich bei Patienten mit WBS häufig ist. Unsere Ergebnisse könnten zur genaueren Definition der diagnostischen Kriterien und für Empfehlungen der Nachsorge von WBS-Patienten beitragen.SummaryBACKGROUND: Williams-Beuren syndrome is a multisystem developmental disorder caused by a microdeletion at chromosome 7q11.23. In its classic form it includes dysmorphic facial features, joint contractures, retardation of growth and mental development, gregarious personality, visuospatial cognitive deficits, hypercalcemia, primary or secondary hypertension and cardiovascular disorders. AIM: Clinical diagnosis of Williams-Beuren syndrome can be a challenge in young patients if none of the characteristic cardiovascular features, i.e. supravalvular aortic stenosis or pulmonary artery stenosis, are present. Our aim was to demonstrate the changes in cardiovascular lesions during the postnatal development of Williams-Beuren patients and to follow all cardiovascular findings beyond the most common ones. METHODS: The cardiovascular status of 29 patients with Williams-Beuren syndrome (mean age 12.8 years) was recorded in correlation with age. RESULTS: Cardiovascular diagnoses changed in the majority (72.4%) of patients. Interestingly, 44.8% of the patients had periods with no reported cardiovascular disease. Furthermore, 65.5% of the patients experienced periods when none of the typical cardiovascular lesions, i.e. diffuse or localized supravalvular aortic stenosis and/or pulmonary artery stenosis, were detected. Spontaneous regression and progression of both supravalvular aortic stenosis and pulmonary artery stenosis were observed. An unexpectedly high frequency (41%) of mitral valve disorders was found. CONCLUSIONS: Our study showed that temporary absence of and changes in cardiovascular findings are frequent in Williams-Beuren syndrome. These results could contribute to the refinement of diagnostic criteria and recommendations for cardiovascular follow-up of patients with this syndrome.

The role of dental evaluation and cephalometric analysis in the diagnosis of Williams-Beuren syndrome.

SummaryWilliams–Beuren syndrome (WS) is a genetic condition with an incidence of 1 in 20,000–50,000 live births. The syndrome consists of supravalvular aortic stenosis, characteristic dysmorphic facial features named “elf face” and intellectual disability. Early diagnosis of the syndrome is important since many of its features require treatment, and the prognosis can be dramatically improved by early recognition and management. This developmental disorder is well known to be clinically heterogeneous, making diagnosis difficult if based on the clinical picture. However, genetic testing is expensive and it is not cost-effective to screen all patients based on clinical suspicion. Our goal was to develop a novel clinical screening method that would be sensitive, specific, inexpensive and readily available. We performed cephalometric analysis and dental evaluation of 33 patients with genetically proven WS. Cephalometric analysis of soft tissues showed that with normal SNA, SNB and ANB angles, the lips were in front of the line of harmony. This finding was present in all WS patients (n = 33) but in none of the age-matched controls (n = 100). No other differences were found between WS and control patients. This cephalometric finding is specific and sensitive for WS and can be used in the diagnostic procedure, whereas none of the conventional dental evaluations are useful.

Novel Possible Pharmaceutical Research Tools: Stem Cells, Gene Delivery and their Combination

Both stem cell research and gene delivery are very promising fields of todays biomedical research. In the present review we first attempt to summarize the state of the art in stem cell research. We describe the major categories of stem cells based on cell sources: embryonic, fetal, postnatal and induced pluripotent stem cells. We then present new data on stem cell cultures of dental pulp origin as examples of the progress of postnatal stem cell research. Afterwards, we briefly summarize the most promising achievements in the field of gene delivery. As an example of such advances, we describe novel in vitro and in vivo gene delivery studies to demonstrate that salivary glands are highly potential targets for gene therapy: they can be used to produce therapeutic peptides delivered either into the oral cavity or into the systemic circulation. Finally, we describe and compare studies combining the use of stem cells and gene delivery. We conclude that stem cell therapy and gene delivery alone are both very exciting research areas, and they may act in synergy when used in combination.

Complex analysis of multiple single nucleotide polymorphisms as putative risk factors of tooth agenesis in the Hungarian population

Abstract Objectives. The role was studied of multiple single nucleotide polymorphisms in tooth agenesis in the Hungarian population using a complex approach. Methods. Eight SNPs, PAX9 -912 C/T, PAX9 -1031 A/G, MSX1 3755 A/G, FGFR1 T/C rs881301, IRF6 T/C rs764093, AXIN2-8150 A/G, AXIN2-8434 A/G and AXIN2-30224 C/T, were studied in 192 hypodontia and 17 oligodontia cases and in 260 healthy volunteers. Case-control analysis was performed to test both allelic and genotypic associations as well as associations at the level of haplotypes. Multivariate exploratory Bayesian network-based multi-level analysis of relevance (BN-BMLA) as well as logistic regression analysis were performed. Results. Conventional statistics showed that PAX9 SNP -912 C/T and the MSX1 SNP changed the incidence of hypodontia, although after Bonferroni correction for multiple hypothesis testing, the effects were only borderline tendencies. Using a statistical analysis better suited for handling multiple hypotheses, the BN-BMLA, PAX9 SNPs clearly showed a synergistic effect. This was confirmed by other multivariate analyses and it remained significant after corrections for multiple hypothesis testing (p < 0.0025). The PAX9-1031-A-PAX9-912-T haplotype was the most relevant combination causing hypodontia. Interaction was weaker between PAX9 and MSX1, while other SNPs had no joint effect on hypodontia. Conclusion. This complex analysis shows the important role of PAX9 and MSX1 SNPs and of their interactions in tooth agenesis, while IRF6, FGFR1 and AXIN2 SNPs had no detectable role in the Hungarian population. These results also reveal that risk factors in hypodontia need to be identified in various populations, since there is considerable variability among them.

Tuberculate and odontoma type supernumerary teeth

An 8-and-a-half-year-old girl with supernumerary teeth of tuberculate and odontoma type is described. Treatment of the patient is carried out on conventional lines with a combination of surgical and orthodontic methods. The upper tuberculate type supernumerary teeth were extracted and, after surgical exposure, the upper permanent first incisors were aligned with removable appliances. After secondary dentition was completed, the lower odontoma type supernumerary tooth was removed surgically, and also the maxillary and mandibular first premolars were extracted because of severe crowding, and fixed orthodontic appliances were used to align the permanent dentition. Early diagnosis and treatment of this anomaly is necessary to avoid more serious consequences and to prevent severe orthodontic disturbances.

The Management of Crown Fracture of Immature Teeth by MTA and Calcium Hydroxide: Case Reports

This article describes the treatment of immature maxillary central incisors associated with complicated crown fracture with periapical lesion in two clinical cases. For the first, the root-canal was filled with Ca(OH)2 (calcium hydroxide) as an interim dressing followed by mineral trioxide aggregate (MTA). In the second case, an incomplete obturation of left maxillary central incisor, the root canal was filled with calcium hydroxide. The advantages and disadvantages of Ca(OH)2 and MTA are discussed. Both materials are effective in the treatment of immature teeth. The advantages of MTA demonstrate its potential for replacing calcium hydroxide in endodontic procedures in the near future.