Anne C. O'Connell

Hyper-IgE Syndrome with Recurrent Infections — An Autosomal Dominant Multisystem Disorder

BACKGROUND The hyper-IgE syndrome with recurrent infections is a rare immunodeficiency characterized by recurrent skin and pulmonary abscesses and extremely elevated levels of IgE in serum. Associated facial and skeletal features have been recognized, but their frequency is unknown, and the genetic basis of the hyper-IgE syndrome is poorly understood. METHODS We studied 30 patients with the hyper-IgE syndrome and 70 of their relatives. We took histories, reviewed records, performed physical and dental examinations, took anthropometric measurements, and conducted laboratory studies. RESULTS Nonimmunologic features of the hyper-IgE syndrome were present in all patients older than eight years. Seventy-two percent had the previously unrecognized feature of failure or delay of shedding of the primary teeth owing to lack of root resorption. Common findings among patients were recurrent fractures (in 57 percent of patients), hyperextensible joints (in 68 percent), and scoliosis (in 76 percent of patients 16 years of age or older). The classic triad of abscesses, pneumonia, and an elevated IgE level was identified in 77 percent of all patients and in 85 percent of those older than eight. In 6 of 23 adults (26 percent), IgE levels declined over time and came closer to or fell within the normal range. Autosomal dominant transmission of the hyper-IgE syndrome was found, but with variable expressivity. Of the 27 relatives at risk for inheriting the hyper-IgE syndrome, 10 were fully affected, 11 were unaffected, and 6 had combinations of mild immunologic, dental, and skeletal features of the hyper-IgE syndrome. CONCLUSIONS The hyper-IgE syndrome is a multisystem disorder that affects the dentition, the skeleton, connective tissue, and the immune system. It is inherited as a single-locus autosomal dominant trait with variable expressivity.

Safety and efficacy of adenovirus-mediated transfer of the human aquaporin-1 cDNA to irradiated parotid glands of non-human primates.

This study evaluated the safety and efficacy of a single administration of a recombinant adenovirus encoding human aquaporin-1 (AdhAQP1) to the parotid glands of adult rhesus monkeys. In anticipation of possible clinical use of this virus to correct irradiation damage to salivary glands, AdhAQP1 was administered (at either 2 × 109 or 1 × 108 plaque-forming units/gland) intraductally to irradiated glands and to their contralateral nonirradiated glands. Radiation (single dose, 10 Gy) significantly reduced salivary flow in exposed glands. Virus administration resulted in gene transfer to irradiated and nonirradiated glands and was without untoward local (salivary) or systemic (sera chemistry, complete blood count) effects in all animals. However, the effect of AdhAQP1 administration varied and did not result in a consistent positive effect on salivary flow rates for all animals under these experimental conditions. We conclude that a single adenoviral-mediated gene transfer to primate salivary glands is well-tolerated, although its functional utility in enhancing fluid secretion from irradiated parotid glands is inconsistent.

Radiation-Induced Progressive Decrease in Fluid Secretion in Rat Submandibular Glands Is Related to Decreased Acinar Volume and Not Impaired Calcium Signaling

The mechanism(s) of radiation-induced salivary gland dysfunction is poorly understood. In the present study, we have assessed the secretory function (muscarinic agonist-stimulated saliva flow, intracellular calcium mobilization, Na+/K+/2Cl- cotransport activity) in rat submandibular glands 12 months postirradiation (single dose, 10 Gy). The morphological status of glands from control and irradiated rats was also determined. Pilocarpine-stimulated salivary flow was decreased by 67% at 12 months (but not at 3 months) after irradiation. This was associated with a 47% decrease in the wet weight of the irradiated glands. Histological and morphometric analysis demonstrated that acinar cells were smaller and occupied relatively less volume and convoluted granular tubules were smaller but occupied the same relative volume, while intercalated and striated ducts maintained their size but occupied a greater relative volume in submandibular glands from irradiated compared to control animals. In addition, no inflammation or fibrosis was observed in the irradiated tissues. Carbachol- or thapsigargin-stimulated mobilization of Ca2+ was similar in dispersed submandibular gland cells from control and irradiated animals. Further, [Ca2+]i imaging of individual ducts and acini from control and irradiated groups showed, for the first time, that mobilization of Ca2+ in either cell type was not altered by the radiation treatment. The carbachol-stimulated, bumetanide-sensitive component of the Na+/K+/ 2Cl- cotransport activity was also similar in submandibular gland cells from control and irradiated animals. These data demonstrate that a single dose of gamma radiation induces a progressive loss of submandibular gland tissue and function. This loss of salivary flow is not due to chronic inflammation or fibrosis of the gland or an alteration in the neurotransmitter signaling mechanism in the acinar or ductal cells. The radiation-induced decrease in fluid secretion appears to be related to a change in either the water-handling capacity of the acini or the number of acinar cells in the gland.

Primary failure of tooth eruptionA unique case

Primary failure of tooth eruption rarely occurs. This case represents a rare clinical situation and appears to reflect a generalized disturbance in the eruptive process, inasmuch as (1) deciduous and permanent dentition are affected, (2) incisors, molars, and premolars are involved in all quadrants, (3) skeletal and craniofacial growth are within normal limits, and (4) no systemic/genetic anomalies were detected. This is the first such case reported in the literature; diagnosis and management are discussed.

Pilocarpine Alters Caries Development in Partially-desalivated Rats

This study examined the effect of pilocarpine on caries and saliva composition in rats with compromised salivary gland function. Eight litters of specific-pathogen-free female Sprague-Dawley rats were divided into five groups for surgery. Partial desalivation was performed in either of three ways: (1) Both parotid ducts were ligated; (2) both submandibular/sublingual (SM/SL) glands were excised; or (3) one parotid duct was ligated, and submandibular/ sublingual glands were removed unilaterally. Completely desalivated animals and unoperated animals served as positive and negative controls, respectively. One week following surgery, groups were subdivided so that half of each group had osmotic pumps implanted which delivered pilocarpine HCl (24 mg/kg/day). All animals were infected with Streptococcus sobrinus 6715 and fed cariogenic diet ad libitum for 28 days. Caries scores, microbiological data, and saliva flow rate and composition were determined for all animals. Animals which had both SM/SL glands removed and received pilocarpine developed significantly lower sulcal caries (p ≤0.05) compared with the animals that had both SM/SL removed but did not receive pilocarpine. The concentration of protein in parotid saliva in these pilocarpine-treated animals was unaffected, and nodif f erences were observed in the electrophoretic profiles on SDS-PAGE. Pilocarpine appears to exert its greatest caries-protective effect when the parotid glands remain intact.

Recurring oral giant cell lesion in a child with X-linked hypophosphatemic rickets : clinical manifestation of occult parathyroidism ?

A 9-year-old boy with X-linked hypophosphatemic rickets had a recurring oral giant cell lesion. These lesions are relatively uncommon in children and represent a potentially aggressive disorder that is microscopically indistinguishable from the brown tumors of hyperparathyroidism. Subclinical hyperparathyroidism is not uncommon in X-linked hypophosphatemic rickets and may account for the giant cell lesion in this patient.

Agonist-induced Ca2+ mobilization in the rat submandibular gland during aging and subsequent to chronic propranolol treatment

The effects of age and chronic propranolol treatment on the agonist-induced rise in intracellular free Ca2+ ([Ca2+]i), an index for the coupling of receptor-second messenger generation, was studied using a dispersed rat submandibular gland preparation. Muscarinic stimulation (10 microns carbachol) caused a rapid (T1/2 less than 2 s) and dramatic (approximately 4.5-fold) rise in [Ca2+]i followed by a lower sustained increase (approximately 3-fold) in [Ca2+]i as measured directly with the Ca(2+)-sensitive fluorescent probe, fura-2. The magnitude and the rate of increase of the initial rise in [Ca2+]i and the level of the sustained increase in [Ca2+]i were not different between 2- an 21-month-old rats. Stimulation in a Ca(2+)-free medium reduced the initial agonist-induced increase in [Ca2+]i by approximately 35-40%, while the sustained increase was abolished by the removal of extracellular Ca2+ from cells in both young and old rats. Chronic treatment for 30 days with 20 mg/kg propranolol, a beta-adrenergic antagonist, did not significantly alter the ability of dispersed submandibular cells in old rats to mobilize Ca2+ during agonist stimulation or influence the in vivo stimulated gland output. These results suggest that the agonist-induced rise in [Ca2+]i is not altered by aging or by chronic treatment of aged rats with propranolol and, therefore, receptor-second messenger coupling remains intact.

Successful Restoration of Severely Mutilated Primary Incisors Using a Novel Method to Retain Zirconia Crowns - Two Year Results.

AIM This manuscript describes a simple reliable technique for restoring severely mutilated primary anterior teeth. A rigid glass ionomer post is created over which zirconia crowns can be fitted to achieve a long-term stable esthetic restoration for primary anterior teeth. STUDY DESIGN Children aged 2-5 years with two up to six extensively decayed upper primary incisors were included. Fuji IX was condensed into an intracanal space created to a depth of 3mm, to provide a core which also extended 3mm supragingivally. Crown preparations were completed upon these cores. Zirconia crowns (Nusmile, Houston Texas USA) were fitted and cemented over the prepared cores. All patients were recalled at regular intervals. RESULTS Twenty-three healthy children with 86 restorations participated in the study. The overall survival of the restorations was 95.3% after 12 months and 80.2% after 24 months. According to Kaplan-Meier survival analysis, the median survival time was not reached while the estimated mean survival time was 22.9 months. CONCLUSIONS This newly described clinical technique is simple and reliable to use for restoration of extensively decayed primary incisors. Use of zirconia crowns retained using this technique offers superior esthetic, durable restorations with remarkable gingival response up to 24 months.

Casein phosphopeptide-amorphous calcium phosphate products in caries prevention

Data sourcesMedline, Embase, PreMedline and Cochrane Central Register of Controlled Trials.Study selectionClinical trials, investigating only clinical caries outcomes on participants of any age comparing the use of Tooth Mousse® or Tooth Mousse Plus® to a routine oral care regimen for the prevention of dental caries with or without comparison to additional preventive products. Studies that used other formulations of CCP-ACP were excluded. Trials using split-mouth design were also excluded. Only English language papers were considered.Data extraction and synthesisPapers were assessed independently by both authors using the Cochrane Collaboration tool for assessing risk of bias in randomised trials.1 Meta-analysis was not possible due to study heterogeneity.ResultsTwelve studies were available for the final review; three studies on caries prevention were assessed as having low risk of bias. The remaining nine studies, with high risk of bias, reported on treatment or regression of early carious lesions. Two RCTs reported no significant benefits in the use of Tooth Mousse® over brushing with a fluoride toothpaste, a third study demonstrated a statistically significant increase in enamel microhardness for the Tooth Mousse® group compared to control group but no difference to the group who had fluoride gel treatment. Overall the authors concluded that Tooth Mousse® performs no better than fluoride in the prevention of carious lesions.Seven of nine studies evaluated caries lesion severity in orthodontic patients, with four demonstrating statistically significant white spot regression. Two trials in non-orthodontic patients showed statistically significant remineralising potential of Tooth Mousse® over fluoride mouthrinse or the regular use of fluoride toothpaste in 14-30 days.ConclusionsThe authors found no evidence to support the use of Tooth Mousse® over brushing with a fluoride toothpaste for the prevention of early caries. ToothMousse® appeared to benefit regression of white spot lesions associated with orthodontic treatment but the evidence is limited. Effectiveness of Tooth Mousse® was not significantly increased by the addition of fluoride in Tooth Mousse Plus® and evidence is still lacking to support the use of one over another. High quality randomised clinical trials are needed before these products can be recommended for the prevention and treatment of early carious lesions in the general population.Source of fundingThe publication was funded by Colgate Palmolive, Australia.

Selective Reduction of Talon Cusps- A Case Series

Talon cusps associated with permanent incisors are a rare occurrence but can cause numerous complications. When treatment is indicated options include radical or selective reduction of the accessory cusp, but there is no standard protocol for management. STUDY DESIGN Patients referred to the Dublin Dental University Hospital for treatment of talon cusps were identified, contacted and consent obtained. Clinical notes, photographs and radiographs were retrospectively reviewed. RESULTS Eleven patients with 14 talon cusps were identified. The age ranged from 8-15 with a mean of 11 years. Four teeth had radical talon cusp reduction carried out and 10 teeth underwent selective reduction. Follow up ranged from 3-66 months. Technical information from these cases was used to devise a protocol for selective reduction. CONCLUSIONS Selective reduction is a valuable technique for managing talon cusps. It is a conservative approach which can be employed before an incisor has reached maturity and is acceptable in young children.