Lateral incisor agenesis predicts maxillary hypoplasia and Le Fort I advancement surgery in cleft patients.

BACKGROUND: Severe maxillary hypoplasia in cleft patients is caused by a combination of pathogenic and iatrogenic factors. In this work, the authors investigated anatomical deficiencies in dentition for predicting Le Fort I maxillary advancement surgery for severe maxillary hypoplasia in cleft patients. METHODS: Cleft lip-cleft palate and cleft palate patients older than 14 years of age were reviewed for demographics, dental anomalies, and Le Fort I advancement. Chi-square tests, t tests, and multivariate logistic regression analyses were performed to delineate the contribution of quantity and position of dental agenesis to maxillary advancement surgery. RESULTS: In the 114 patients reviewed (mean age, 19.2 years), 64.0 percent were male patients, 71.9 percent had dental agenesis, and 59.6 percent required Le Fort I advancement. In patients who did not exhibit dental agenesis, 18.8 percent required Le Fort I advancement compared with 74.4 percent of patients with dental agenesis (p < 0.0001). Le Fort I advancement surgery was increased to 76.3 percent when dental agenesis was at the lateral incisor position (p < 0.0001) and 86.4 percent when patients were missing two or more teeth (p < 0.0001). Both sella-to-nasion-to-A point angle (p = 0.003) and A point-to-nasion-to-B point angle (p = 0.04) measurements were decreased in patients missing dentition at the lateral incisor position. Adjusting for multiple missing teeth and orthodontic compensations, multivariate logistic regression analyses demonstrated that lateral incisor agenesis is an independent predictor for Le Fort I advancement surgery (OR, 4.4; 95 percent CI, 1.42 to 13.64; p = 0.01). CONCLUSIONS: Lateral incisor agenesis correlated to maxillary hypoplasia and independently predicted the need for Le Fort I advancement in cleft patients, potentially as an anatomical readout of intrinsic growth deficiency. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Resorption of PDLLA plates as a nidus for recurrent langerhans cell histiocytosis.

Resorbable plating systems have been adapted into routine use for craniofacial reconstruction in children. After implantation in some patients, the area around the plates can develop palpable and visible fibrous capsules, with underlying bone resorption and a significant foreign-body giant cell reaction. The reaction is usually self-limited. We report a case in which Langerhans cell histiocytosis was resected, and then recurred at the sites of resorbing plate and screw placement in association with a foreign-body giant cell reaction.

Novel hyperactive glucocorticoid receptor isoform identified within a human population.

Glucocorticoids serve as important therapeutic agents in diseases of inflammation, but clinical use, especially in advanced septic shock, remains controversial because of the unpredictable response. Prior studies correlate human glucocorticoid receptor (hGR) isoforms with a decreased response to steroid therapy. Further analysis of additional hGR isoforms may improve the understanding of the steroid response. Ninety-seven human volunteers' blood samples were surveyed for hGR isoforms. An isoform matching National Center for Biotechnology Informatics (NCBI) hGRα (hGR NCBI) served as a reference. Two isoforms were of particular interest-one isoform had three nonsynonymous single-nucleotide polymorphisms (SNPs) (hGR NS-1), and the second had a single-nucleotide deletion (hGR DL-1) resulting in a truncated protein. Transactivation potentials were measured using a luciferase reporter assay. Human glucocorticoid receptor NS-1 had activity more than twice of hGR NCBI, whereas hGR DL-1 demonstrated less than 10% of the activity of hGR NCBI. Cotransfection of two isoforms revealed that the presence of hGR NS-1 increased transactivation potential, whereas hGR DL-1 decreased activity. Synthetic constructs isolating individual and paired SNPs of hGR NS-1 were created to identify the SNP responsible for hyperactivity. Transactivation studies revealed a SNP within the ligand-binding domain exerted the greatest influence over hyperactivity. In evaluating the response to hydrocortisone, hGR NCBI and hGR NS-1 displayed an increased dose-dependent response, but hGR NS-1 had a response more than twice hGR NCBI. Characterization of the novel hyperactive hGR NS-1 provides insight into a possible mechanism underlying the unpredictable response to steroid treatment.

The effect of CAG repeat length polymorphism in the murine glucocorticoid receptor on transactivation potential.

Severe sepsis remains an important cause of death, particularly among trauma and burn patients. The severity of the systemic inflammatory response after trauma or burns and susceptibility to sepsis vary among individuals. One possible mechanism is through differential effects on glucocorticoid receptor (GR) expression by pro-inflammatory mediators (e.g. lipopolysaccharide signaling). In a mouse burn model, we demonstrated differential GR levels, size, and transcriptional activity in CD14 knockout (KO) mice when compared to wild-type (C57BL/6J) after injury. Sequence analysis revealed only 8 CAG repeats in the GR transactivation domain in the CD14 KO; the wild-type contained seventeen. A survey of genomic DNA from 51 mouse strains demonstrated CAG repeat length range from 7 - 17. We then studied the effect of polymorphism in CAG repeat length on GR activity. Fragments with CAG repeats varying from 8-40 (8, 17, 30, 38, and 40) were engineered and shuttled into the wild-type GR expression vector. The resulting plasmids were then co-transfected with a glucocorticoid response element linked to a luciferase in order to compare their transactivation potentials. Transactivation potential was highest in the 17-CAG GR. The effect of GR polymorphisms on GR activity warrants more research as this data suggests a mechanism for the individual differences in response to steroid treatment and the response to injury.