Assessment of morbidity following insertion of fixed preoperative orthopedic appliance in infants with complete cleft lip and palate.

OBJECTIVE: To examine physiologic and behavioral indicators of pain within the first 24 hours following insertion of the fixed presurgical orthopedic appliance (FPOA) under general anesthesia in infants with unilateral and bilateral complete cleft lip and palate. METHODS: The study sample included 109 infants who had either a dentomaxillary appliance (DMA) or an elastomeric chain premaxillary retraction (ECPR) appliance. Vital signs and FLACC (Face, Legs, Activity, Cry, Consolability) scores were used to measure the outcomes. RESULTS: There was an initial postoperative increase in the median heart rate. Heart rate returned to the median baseline level by 8 hours. The median systolic blood pressure increased postoperatively and remained elevated throughout the time of evaluation. The median respiratory rate remained below that at baseline throughout the study period. The highest mean change in FLACC measurements was observed approximately 2 hours postoperatively. By 3 hours postoperatively, the scores decreased. CONCLUSIONS: Although there was a large individual variability, the FLACC scores became reduced after 3 hours following surgical insertion of the DMA and the ECPR appliance.

Efficient second-harmonic generation and modal dispersion effects in orientation-patterned GaAs waveguides.

Efficient second-harmonic conversion of 4 microm radiation was demonstrated in orientation-patterned GaAs (OPGaAs) waveguides (WGs). An experimentally corrected phase-matching curve for second harmonic generation (SHG) in OPGaAs WGs is presented. Influence of WG modes on the SHG process was studied. Two distinct types of SHG in the waveguides were identified and related to the TE and TM modes. Each type has its own dependence on pump polarization. The 21% W(-1) normalized conversion efficiency is within a factor of 0.75 from the predicted value for an ideal WG.

The angiogenesis inhibitor tnp-470 effectively inhibits human neuroblastoma xenograft growth, especially in the setting of subclinical disease.

Tumor vascularity is highly correlated with disease outcome in neuroblastoma. Thus, novel therapeutics that target the vascular endothelium are candidates for incorporation into clinical trials. We therefore examined the effect of TNP-470 on human neuroblastoma growth in mouse models reflecting both clinically evident and minimal disease. Mice were inoculated s.c. or by tail vein injection with 10(7) human neuroblastoma-derived CHP-134 cells and treated with TNP-470 (100 mg/kg/dose s.c. three times a week or by continuous infusion) or saline. Treatment was given as a single agent in established xenografts, 10 days after 450 mg/kg of cyclophosphamide, or 12 h after tumor inoculation. Tumor growth rate was markedly inhibited in mice receiving TNP-470 administered alone both s.c. and by continuous infusion with a treatment to control ratio (T:C) at day 16 of 0.3 (P < 0.001) and a T:C at day 30 of 0.4 (P = 0.029) for each dosing method, respectively. TNP-470 also significantly inhibited tumor growth when administered following cyclophosphamide (T:C at day 30 = 0.2, P < 0.001) and inhibited disease establishment when given shortly after xenograft inoculation (T:C at day 30 = 0.1, P < 0.001) or tail vein injection. TNP-470 was shown to directly inhibit angiogenesis by Matrigel assay (P =.010) and to increase the apoptotic index in treated tumors. These data show that TNP-470 is a potent inhibitor of human neuroblastoma growth rate and tumorigenicity. We speculate that TNP-470 may be a useful adjuvant therapy for high-risk neuroblastoma patients, particularly when used in settings of minimal disease status.

Angiogenesis inhibitor TNP-470 during bone marrow transplant: safety in a preclinical model.

High-dose therapy with stem cell rescue is a treatment option for patients with advanced solid tumors. Although this approach has promise for some pediatric cancers, especially neuroblastoma, it is limited by the risk of relapse posttransplant as well as concern about possible reinfused tumor cells in autologous stem cell products. Antiangiogenic agents given during and after recovery from high-dose therapy with stem cell rescue may decrease the risk of relapse. TNP-470 is an antiangiogenic agent now in clinical trials. Although it inhibits the growth of bone marrow (BM) colony-forming cells in vitro, no significant hematological toxicity has been seen in Phase I trials. To assess the feasibility of using antiangiogenic agents during the period of posttransplant hematopoietic engraftment, we have developed a model of stem cell transplant in mice. Mice were lethally irradiated and then rescued with stem cells containing a transgene expressed in the hematopoietic lineage. Mice were then treated with TNP-470 or placebo, and assessed for survival, successful engraftment, and kinetics of engraftment. Both treated and control mice demonstrated reliable multilineage engraftment as well as normal lymphoid maturation with no excess mortality in the treated group. WBCs were lower but still within the normal range at d+28 in mice treated with bolus TNP-470, but not in those treated with continuous infusion TNP-470, compared with controls. These data indicate that inhibitors of angiogenesis do not adversely impact engraftment after stem cell transplantation.

Localization of a hereditary neuroblastoma predisposition gene to 16p12-p13.

BACKGROUND: Hereditary predisposition to develop neuroblastoma segregates as an autosomal dominant Mendelian trait. PROCEDURE: We have performed linkage analysis on 10 families with neuroblastoma to localize a hereditary neuroblastoma predisposition gene (HNB1). RESULTS: A single genomic interval at chromosome bands 16p12-p13 was consistent with linkage (lod = 3.46), and identification of informative recombinants defined a 25.9-cM critical region between D16S748 and D16S3068. Loss of heterozygosity was identified in 5/12 familial (42%) and 55/259 nonfamilial (21%) neuroblastomas at multiple 16p polymorphic loci. A 12.8-cM smallest region of overlap of deletions was identified within the interval defined by linkage analysis (tel-D16S764-D16S412-cen). CONCLUSIONS: Taken together, these data suggest that HNB1 is located at 16p12-p13 and that inactivation of this gene may contribute to the pathogenesis of nonfamilial neuroblastomas.

Inhibition of tumor growth in a human neuroblastoma xenograft model with TNP-470.

UNLABELLED: Background and Procedure High-risk neuroblastoma disease features are correlated with tumor vascularity, suggesting that angiogenesis inhibitors may be a useful addition to current therapeutic strategies. We therefore examined the efficacy of TNP-470 (TAP Pharmaceuticals, Deerfield, IL) in human neuroblastoma xenograft models. RESULTS: Tumor growth rate was markedly inhibited in mice receiving TNP-470 administered alone with a treatment to control ratio (T/C) at day 21 = 0.4 (P <.001). TNP-470 also significantly inhibited tumorigenicity when administered shortly after xenograft inoculation (T/C at day 30 = 0.1, P <.001) and when administered following cyclophosphamide (T/C at day 35 = 0.1, P <.001). CONCLUSIONS: These data show that TNP-470 is a potent inhibitor of human neuroblastoma growth both alone and when given with conventional chemotherapy, suggesting that it may be a useful adjunctive therapy for high-risk neuroblastoma patients.

Long term survivors of childhood leukemia.

Changes in therapy, primarily intensification, for childhood leukemias have significantly improved cure rates during the past 30 years. The increasing number of survivors has led to a heightened appreciation of the late complications of treatment caused by both radiation and chemotherapy. Important late effects include decreased growth, poor school performance, altered cardiac function, infertility, and second malignant neoplasms. The long term outcome of children and adolescents suffering from the most recently recognized acute complication of treatment, avascular necrosis of weight-bearing bones, is still not known. These, and all patients treated on clinical trials, should be followed throughout their lives. Many of the complications of treatment are often not realized until years after the completion of therapy; some have been found to be related to dose intensity, emphasizing the importance of clinical trials that examine reduction of therapy for diseases with excellent cure rates. A successful example of this strategy is the elimination or reduction of radiation dose for the prevention of central nervous system acute lymphocytic leukemia. This has resulted in fewer long term central nervous system complications without a decrease in survival rates. As knowledge of late effects increases, design of future trials will need to focus on striking a balance between cure and long term toxicity.

Microbiological findings in prepubertal periodontitis. A case report.

Generalized pre-pubertal periodontitis (GPP) is a rare entity that usually affects children with severe systemic diseases. We report the case of a 7-year-old male patient diagnosed with GPP, with no apparent systemic condition, who lost all his primary teeth to periodontal disease. Before extractions, while he was still in mixed dentition the subgingival plaque was collected and analyzed using DNA probes to 40 different microorganisms. Putative periodontopathogens such as Prevotella intermedia, Selenomonas noxia, Fusobacterium nucleatum, and Actinobacillus actinomycetemcomitans could be identified throughout the mouth. More intriguing was the colonization of the sulcus of some secondary teeth by potentially harmful microorganisms found in pockets of diseased adjacent primary teeth.

Delayed dental maturation in cleidocranial dysplasia.

Cleidocranial dysplasia (CCD), a rare, inherited, generalized, skeletal and dental dysplasia, exhibiting an autosomal dominant mode of transmission, may be associated with delays during tooth maturation. To test whether permanent tooth formation is delayed in patients with CCD and if the presence of supernumerary teeth adversely influences maturation of the dentition, a group of CCD patients (eight females, three males) was compared to an equal number of control subjects matched for age and gender. Dental maturity was assessed using panoramic radiographs and the Dental Maturity Ratio, (DMR = mean dental age divided by the chronological age) was calculated. The mean DMR in CCD patients (0.87 +/- 0.14) was lower than in the control group (1.06 +/- 0.14), p < 0.01. Among patients with CCD, patients with supernumerary teeth, had a lower DMR (0.82 +/- 0.13 vs. 0.91 +/- 0.16), but the difference did not reach statistical significance. After adjusting for the presence of supernumerary teeth the diagnosis of CCD was still found to be associated with lower DMR than controls, p = 0.0569. We conclude that CCD patients have delayed tooth development of approximately 2.1 years and that among these patients, those with supernumerary teeth were further delayed by 1.5 years.

Morphometric analysis of the primary and permanent dentitions in hemifacial microsomia: a controlled study.

Hemifacial microsomia (HFM), a developmental abnormality involving the first and second branchial arches, is one of the most common craniofacial abnormalities. Although the general presentations of hemifacial microsomia--such as unilateral microtia, macrostomia, and hypoplasia of the mandibular ramus and condyle--are wellknown, the effects on the teeth are not well-documented. This study examined the primary and permanent tooth dimensions of dental casts of 50 hemifacial microsomia patients compared with those of 50 normal control patients matched for sex and dental status. The results showed that the mesiodistal dimensions of the mandibular second primary molar and the mandibular permanent first molar teeth on the affected side in hemifacial microsomia were significantly smaller compared with those of control teeth (p < 0.001). Furthermore, in the maxillary and mandibular first permanent molars and the maxillary and mandibular first and second primary molars, the teeth in the apparently "normal" side of hemifacial microsomia were also significantly reduced in the mesiodistal dimensions. Comparison of overall dimensions revealed that all primary and permanent molars in hemifacial microsomia were significantly smaller in the mesiodistal dimensions compared with control teeth. A general gradient effect was observed, with the most posterior tooth in each arch being the most severely affected and no effect being seen in the canines and the incisors. These findings suggest that the dental lamina in hemifacial microsomia is affected, and support the hypothesis that its pathogenesis involves an abnormality of the neural crest. Furthermore, these results also support the concept that hemifacial microsomia is a bilateral rather than a unilateral condition.

Emergency management of oral trauma in children.

Oral trauma continues to be a common pediatric emergency, accounting for 150 emergency room dental consultations per year at Children's Hospital in Boston. Children between the ages of 18 months and 2.5 years and between 8 and 11 years are most at risk. Recent advances in the management of these dental emergencies may help children and their families avoid the psychological and financial cost of infection or loss of primary and permanent teeth. Treatment of avulsions in the young permanent dentition remains a common problem, and a universally accepted approach to its management is still evolving. The use of a doxycycline immersion prior to reimplantation by the dentist may be helpful in preventing external root resorption. As always, the best therapy against dentofacial trauma is the pediatrician's support of preventive measures.

Developmental dental changes in isolated cleft lip and palate.

Isolated cleft lip and/or palate, CL(P), may be associated with multiple changes in the developing dentition. To test the hypothesis that permanent tooth formation is delayed in patients with CL(P), dental maturity was assessed from panoramic radiographs. The dental maturity ratio (DMR, dental age divided by chronological age) of a group of CL(P) patients (23 girls, 30 boys) was compared with matched control subjects (38 girls, 41 boys). The mean DMR in cleft boys (0.97 +/- 0.01) was significantly lower than in control boys (1.06 +/- 0.01), P < 0.05. The mean DMR in cleft boys was lower than in cleft girls (1.02 +/- 0.02), with a tendency toward statistical significance. No significant difference in DMR was found between the cleft versus control girls, or between the control girls and boys. Among cleft boys, the prevalence of dental age delay was 67% (20/30), with a mean delay of 0.6 +/- 0.4 years. These results suggested that CL(P) may be associated with delay in permanent tooth formation.

Spectrum of dentin dysplasia in a family: case report and literature review.

The dentin dysplasias (DD), which may be classified as type 1 (DD1) or type 2 (DD2), form a group of rare, inherited dentin abnormalities that are clinically distinct from dentinogenesis imperfecta. Studies of affected families may help to distinguish different types of DD and provide further insight into their etiology and clinical management. This report describes a family that showed characteristic dental features of DD1, including clinically normal crowns in both primary and permanent dentitions, and mobile teeth that may be associated with premature exfoliation. Radiographic features included calcification of the pulp with crescent-shaped, radiolucent pulp remnants, short, tapering, taurodontic roots, and many periapical pathoses that may be cysts or granulomas. A spectrum of dentin dysplasia was noted within the family. Strategies to prevent pulp and periapical infections and early exfoliation of the teeth include meticulous oral hygiene and effective caries-preventive measures.

Adaptation and verification of the relocatable Gill-Thomas-Cosman frame in stereotactic radiotherapy.

PURPOSE: Stereotactic radiotherapy (SRT) combines techniques of stereotactic radiosurgery (SRS) with radiation therapy fractionation schemes. Fractionation in SRT necessitates a relocatable immobilization system to precisely reproduce the patient's position at each treatment. The Gill-Thomas-Cosman (GTC) head frame is such an immobilization device compatible with the Brown-Roberts-Wells (BRW) stereotactic system. We describe this device, our modifications to the original design, the repeat position accuracy, and the daily verification procedure. METHODS AND MATERIALS: The original GTC frame was tested on volunteers. This testing led to an improved strapping system, the decision to construct the oral fixation appliance at our dental clinic, and the construction of a depth confirmation helmet to rapidly confirm the position of the frame on a daily basis. The GTC frame, at our institution, is not acceptable for children requiring anesthesia, and a new frame, the "Boston Childrens' Hospital" frame, was designed. This device uses the base ring of the GTC frame. Airway access is maintained through fixation on the nasal-glabellar region and the ear canal rather than the hard palate and upper gingiva. RESULTS: The modifications of the GTC frame and the verification protocol result in repeat positioning of the frame with respect to the patient anatomy, with a standard deviation of 0.4 mm for both the modified GTC frame and the Boston Childrens' Hospital frame. The relocatibility of the frames has been established in over 2,000 patient setups in over 60 patients to date. DISCUSSION: The GTC frame is a noninvasive and versatile fixation system that provides patient comfort, as well as accurate relocatibility for SRT. The frame is not appropriate for single fraction radiosurgery, as a large setup error (> 2 mm) for a single treatment cannot be excluded. The GTC frame is compatible with the BRW system, and treatment planning for SRT and SRS patients is identical. We currently treat 10-13 SRT patients per day with intracranial neoplasms on a dedicated stereotactic therapy unit. In addition, the Boston Childrens' Hospital frame allows the use of stereotactic therapy in the treatment of children under 6 years of age. This population will benefit especially from precise and highly focal cranial irradiation.

Latex allergies in children with spina bifida: relevance for the pediatric dentist.

Latex is ubiquitous in pediatric dentistry and medical practice. Children with spina bifida and other urogenital abnormalities are at great risk for hypersensitivity reactions during dental treatment. Four representative cases of children with latex allergies at one institution are presented. A latex-avoidance protocol is presented with suggested instrument and equipment alternatives.