Primary failure of eruption of teeth in two siblings with a novel mutation in the PTH1R gene.

BACKGROUND: Primary failure of tooth eruption (PFE) is a rare non-syndromic disorder with prematurely ceased eruption of the posterior teeth, despite clearance by bone resorption of the eruption path. It is generally agreed that most of the impacted teeth are second molars that are deeply seated, and without symptoms. Traditionally, patients with failure of tooth eruption undergo surgical and/or orthodontic treatment. However, patients with PTH1R mutations have no beneficial effect of such a regime and PFE is therefore important to diagnose. CASE REPORT AND FOLLOW-UP: A family with three PFE affected members in two generations, involving both the primary and permanent dentitions, and a novel mutation in the PTH1R gene are reported. Furthermore, the treatment of the eruption failure was documented in one of the cases. CONCLUSION: In the present study, the proband initially only had a minor clinical problem, lack of eruption of the primary second left mandibular molar. However, over time several problems appeared in the permanent dentition. Clinical signs of PFE should lead one to look for similar dental problems in related family members and to molecular DNA testing. Confirmation of the diagnosis PFE in young children has the advantage that unnecessary treatment can be avoided, since early orthodontic intervention for these patients is futile. Once growth is complete, several multidisciplinary treatment strategies can partially solve the posterior open bite malocclusion that is characteristic of this disorder. Treatment should be planned in cooperation with specialists who are used to treating PFE patients.

Guidelines for the genetic diagnosis of hereditary recurrent fevers.

Hereditary recurrent fevers (HRFs) are a group of monogenic autoinflammatory diseases characterised by recurrent bouts of fever and serosal inflammation that are caused by pathogenic variants in genes important for the regulation of innate immunity. Discovery of the molecular defects responsible for these diseases has initiated genetic diagnostics in many countries around the world, including the Middle East, Europe, USA, Japan and Australia. However, diverse testing methods and reporting practices are employed and there is a clear need for consensus guidelines for HRF genetic testing. Draft guidelines were prepared based on current practice deduced from previous HRF external quality assurance schemes and data from the literature. The draft document was disseminated through the European Molecular Genetics Quality Network for broader consultation and amendment. A workshop was held in Bruges (Belgium) on 18 and 19 September 2011 to ratify the draft and obtain a final consensus document. An agreed set of best practice guidelines was proposed for genetic diagnostic testing of HRFs, for reporting the genetic results and for defining their clinical significance.

Use of cryopreserved peripheral mononuclear blood cells in biomonitoring.

This study was performed to investigate the effect of storing blood samples by freezing on selected biomarkers and possible implications for biomonitoring. Comparative measurements were performed in order to investigate the use of cryopreserved vs. freshly separated peripheral mononuclear blood cells (PMBC) obtained from donor blood. Measurements of DNA-repair, mutant frequency, and subcell content were included. Samples for large biomonitoring studies are usually taken from study groups within a short time period of days/weeks and storing of study material for later analysis can be necessary. We measured the DNA repair activity as dimethylsulfate induced unscheduled DNA synthesis (UDS) in PMBC incubated with either autologous plasma or fetal bovine serum (FBS). Comparison of the hprt mutant frequency by the T cell cloning assay was made in parallel. Finally the content of B/T-lymphocytes and monocytes was measured in phytohemaglutinin (PHA)-stimulated cultures at different time intervals. The results showed a higher DNA repair activity in cryopreserved samples compared with fresh samples. We also found differences in mutant frequencies with higher values in fresh samples. A significant correlation of frequencies was seen when comparing fresh with cryopreserved samples. Furthermore we recommend fresh human plasma used in UDS incubation media.

DNA damage in isolated rat hepatocytes exposed to C.I. pigment orange 5 and C.I. pigment yellow 12 by the alkaline comet assay.

The induction of DNA damage by commonly used printing ink pigments, C.I. pigment orange 5 (C.I. 12075) and C.I. pigment yellow 12 (C.I. 21090), was investigated in freshly isolated rat hepatocytes with the comet assay. C.I. pigment yellow 12 is a 3,3'-dichlorobenzidine-based diarylide pigment, and C.I. pigment orange 5 is a naphthol-azo pigment. The pigments are virtually insoluble in aqueous solutions, and they have not been tested extensively for toxicological effects. C.I. pigment orange 5 increased the levels of DNA damage at 5 microg/ml (P < 0.02) and C.I. pigment yellow 12 at 20 microg/ml (P < 0.002). The effect of incubation time (20, 40, and 80 min) of the same concentrations of the pigments was tested. The levels of DNA damage were increased up to 80 min. Both pigments produced DNA damage that was in the same range as the food carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline. Our data indicate that both C.I. pigment orange 5 and C.I. pigment yellow 12 are genotoxic in hepatocytes with metabolizing capacities. However, further investigation of the metabolism and disposition are required for the evaluation of the safety of these pigments.

Iatrogenic developmental effects of pediatric intensive care.

Critically ill children in the pediatric intensive care environment are at particular risk for experiencing health care interventions that hinder them from progressing through their normal developmental milestones. Knowledge of the factors that influence iatrogenic developmental insults can help the nurse develop the skills and sensitivity to meet the complex needs of these children and their families.

Histologic evaluation of new attachment in humans. A preliminary report.

This study was designed to evaluate the potential for regeneration of a new attachment (alveolar bone, cementum and a functional periodontal ligament) in patients whose attachment apparatus had been destroyed by periodontal disease. In each of the three parts of the investigation, the most apical level of calculus on the root served as a histologic reference point to measure regeneration. In Part I, attempts were made to initiate the formation of a new attachment by surgical debridement, crown removal (coronectomy) and submersion of the vital root below the mucosa. Nonsubmerged, surgically debrided defects served as controls. In Part II, debrided intrabony defects were treated with and without demineralized freeze-dried bone allograft and the associated vital roots were submerged. Part III evaluated potential for regeneration of a new attachment in nonsubmerged roots with and without the use of demineralized freeze-dried bone allograft. Gingival grafts were placed over the experimental and control sites in an attempt to retard epithelial migration. Biopsies were obtained in 6 months and regeneration was evaluated histometrically. Preliminary results in 7 patients and 24 intrabony defects indicate that new attachment is possible on pathologically exposed root surfaces in a submerged environment with and without the incorporation of demineralized freeze-dried bone allografts. New attachment was observed on pathologically exposed root surfaces in a nonsubmerged environment when intrabony defects were grafted with demineralized freeze-dried bone allograft. New attachment was not observed on nongrafted, nonsubmerged, defects with and without the placement of gingival grafts over the defects.

Effect of periodontal therapy on spontaneous lymphocyte response and neutrophil chemotaxis in localized and generalized juvenile periodontitis patients.

The etiology and pathogenesis of juvenile periodontitis may involve dysfunctions of the host response. In particular, the neutrophil and the lymphocyte have been implicated in the disease. The purpose of the present study was to examine the in vitro spontaneous lymphocyte response and neutrophil chemotaxis in populations of localized juvenile periodontitis (LJP) and generalized juvenile periodontitis (GJP) patients and age- and sex-matched healthy subjects (HS). These laboratory values were also evaluated immediately following and 1 year after periodontal therapy. The results show that spontaneous lymphocyte responses reflecting the autologous mixed lymphocyte reaction (AMLR) are depressed for GJP patients. The decreased AMLR in the GJP group appears to represent an abnormal T-cell function which may reflect activity of the periodontal lesion. LJP patients have an increased AMLR response, although it was not statistically significant. 1 year following active periodontal therapy, spontaneous lymphocyte responsiveness returned to normal in most GJP patients. The increased spontaneous lymphocyte responsiveness of LJP patients was not changed either immediately following active periodontal therapy or 1 year later. LJP and GJP patients exhibited a neutrophil chemotaxis defect when compared to cells from HS. This neutrophil defect was still observed 1 year following active therapy.