Andrew L. Sonis

A Longitudinal Study of Oral Ulcerative Mucositis in Bone Marrow Transplant Recipients

Background. Few longitudinal studies have investigated the onset, duration, and resolution of ulcerative mucositis in bone marrow transplant recipients. This study prospectively followed a group of such patients on a daily basis to obtain data on the incidence of ulcerative mucositis, location and duration of lesions, severity with different conditioning regimens, and the relationship of such mucositis to the absolute neutrophil count.

Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson–Gilford progeria syndrome

Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA that produces the farnesylated aberrant lamin A protein, progerin. This multisystem disorder causes failure to thrive and accelerated atherosclerosis leading to early death. Farnesyltransferase inhibitors have ameliorated disease phenotypes in preclinical studies. Twenty-five patients with HGPS received the farnesyltransferase inhibitor lonafarnib for a minimum of 2 y. Primary outcome success was predefined as a 50% increase over pretherapy in estimated annual rate of weight gain, or change from pretherapy weight loss to statistically significant on-study weight gain. Nine patients experienced a ≥50% increase, six experienced a ≥50% decrease, and 10 remained stable with respect to rate of weight gain. Secondary outcomes included decreases in arterial pulse wave velocity and carotid artery echodensity and increases in skeletal rigidity and sensorineural hearing within patient subgroups. All patients improved in one or more of these outcomes. Results from this clinical treatment trial for children with HGPS provide preliminary evidence that lonafarnib may improve vascular stiffness, bone structure, and audiological status.

Dentofacial development in long‐term survivors of acute lymphoblastic leukemia: A comparison of three treatment modalities

Ninety‐seven children who were diagnosed with acute lymphoblastic leukemia before 10 years of age and treated with chemotherapy alone, chemotherapy plus 1800‐cGy cranial irradiation (RT), or chemotherapy plus 2400‐cGy RT were evaluated for effects of therapy on dentofacial development. All patients were seen at least 5 years postdiagnosis. Dental abnormalities were determined from panoramic radiographs, and craniofacial evaluations were made from lateral cephalometric radiographs. Ninety‐one (94%) of all patients and 41 (100%) of patients younger than 5 years of age at diagnosis had abnormal dental development. the severity of these abnormalities was greater in children who received treatment before 5 years of age and in those who received RT. Observed dental abnormalities included tooth agenesis, arrested root development, microdontia, and enamel dysplasias. Craniofacial abnormalities occurred in 18 of 20 (90%) of those patients who received chemotherapy plus 2400‐cGy RT before 5 years of age. Mean cephalometric values of this group showed significant deficient mandibular development. the results of this study suggest that the severity of dentofacial‐developmental abnormalities secondary to antileukemia therapy are related to the age of the patient at the initiation of treatment and the use of cranial RT.

An evaluation of a fluoride-releasing, visible light-activated bonding system for orthodontic bracket placement

In spite of improved preventive measures, decalcification around bonded orthodontic appliances continues to be a problem for the clinician. Various fluoride-containing mediums have been proposed as aiding in the elimination of this problem; however, almost all are dependent on patient cooperation for their success. An ideal preventive system would be one that would operate independently of patient cooperation. The purpose of the present study was to compare a visible light-activated, fluoride-releasing bonding system with a visible light-activated conventional bonding system relative to bracket retention and prevalence of decalcification. Twenty-two patients were entered into the study, representing 206 experimental brackets and 206 control brackets. The average treatment period was 25 months. No significant differences in bracket retention rates were found between the two systems. Significantly, 26 teeth in the control group demonstrated decalcification (12.6%), whereas none of the teeth in the experimental group did. The results of this study suggest that a visible light-activated, fluoride-releasing bonding system is capable of adequately retaining brackets while aiding in the prevention of decalcification around bonded appliances.

Air abrasion of failed bonded metal brackets: A study of shear bond strength and surface characteristics as determined by scanning electron microscopy

Failed bonded orthodontic brackets generally require their replacement with a new bracket. The introduction of air abrasion (microetching) technology to orthodontics may allow for immediate use of these failed brackets. This study compared the in vitro shear bond strengths of previously failed bonded metal brackets (experimental group) subjected to air abrasion with new untreated brackets (control group). All bonding used a light-cured orthodontic bonding system. In addition, representative samples from each group were examined by scanning electron microscopy. The results of this study found no significant differences in shear bond strengths between the two groups. Scanning electron microscopy examination of the air abraded brackets revealed a roughened mesh surface with residual bonded material in the bracket base. This simple technique should allow for the immediate reuse of previously failed bonded metal brackets.

Oral pathoses as diagnostic indicators in leukemia.

A retrospective chart review of 500 leukemia patients was carried out to analyze the role of oral pathoses in the presentation of leukemia and to determine those factors which affect the frequency of oral involvement during the initial clinical phases of the disease. The data indicate that oral pathoses were frequent signs or symptoms in patients with undiagnosed acute leukemia but were less prevalent in patients with undiagnosed chronic leukemia. Neither age nor sex appeared to be a significant factor affecting oral involvement. Oral signs of thrombocytopenia were the most prevalent complaint of patients seeking diagnosis for their leukemia because of an oral problem, and they were also most frequently responsible for oral problems found at initial physical examination. Head and neck lymphadenopathy was also a frequent presenting sign or symptom. Dentists were responsible for initiating the diagnosis of leukemia in a significant number of patients with acute nonlymphoblastic leukemia.

Children with repaired bilateral cleft lip/palate: effect of age at premaxillary osteotomy on facial growth.

This study compared facial growth in three groups of patients with bilateral complete cleft lip/palate: those who had (1) no premaxillary osteotomy, (2) premaxillary osteotomy before age 8 years, and (3) premaxillary osteotomy after age 8 years. Of 24 children with bilateral complete cleft lip/palate, 7 had early premaxillary osteotomy (mean age, 6.1; range, 3.7 to 7.6 years), 10 had late osteotomy (mean age, 11.2; range, 8.3 to 20.7 years), and 7 did not require premaxillary repositioning and served as controls (mean age, 12.4; range, 6.4 to 17.8 years). Presurgical and postsurgical lateral cephalograms were digitized using the Dentofacial Planner software; most current lateral cephalograms comprised the control group. Forty-one bony and 25 soft-tissue landmarks were digitized, and 8 angles were measured: SNA, (sella-nasion-A point), SNPg (sella-nasion-pogonion), ANB (A point-nasion-B point), NAPg (nasion-A point-pogonion), ST convexity (glabella-subnasale-soft-tissue pogonion), Sn-G vertical (line perpendicular to the horizontal plane dropped from glabella and distance measured from subnasale to this vertical), Cm-Sn-Ls (columella-subnasale-abial superioris), and Sn-Gn-C (subnasale-soft-tissue gnathion-chin point). Statistical difference in mean preoperative and postoperative values were measured with analysis of variance. Tests of significance were adjusted for multiple comparisons using the Bonferroni correction. Mean age at follow-up for early, late, and control groups was 11.8, 14.0, and 12.4 years, respectively. Mean follow-up for early and late groups was 5.7 and 2.8 years. There was a significant preoperative difference among the three groups for mean SNA (p < 0.01), ANB (p < 0.01), and NAPg (p < 0.01). Bonferroni analyses revealed that the early group had significantly greater SNA, ANB, and NAPg angles than the late (p < 0.01) and control groups (p < 0.05). There was a significant postoperative difference among groups for ANB (p < 0.05); Bonferroni analyses also showed that the control group had a significantly greater ANB than the late group (p < 0.05). The t test for equity of means established postoperative change for SNA (p < 0.01), ANB (p< 0.01), NAPg (p < 0.01), and ST convexity (p < 0.01) for the early group was significantly greater than for the late group. Children who required early premaxillary positioning had more significant preoperative deformity; however, this groups postoperative profile was not, on average, significantly different from either the late or control groups. Our findings that the early group had more significant change with premaxillary osteotomy than the late group suggest that premaxillary positioning can be done before completion of facial growth without compromise.

The role of herpes simplex virus in the development of oral mucositis in bone marrow transplant recipients

Herpes simplex virus (HSV) has been implicated as a major etiologic factor in the development of ulcerative mucositis in bone marrow transplant (BMT) recipients. in this study, 60 patients who received BMTs were evaluated for at least 30 days post‐transplant for ulcerative mucositis and the presence of culturable HSV. Fiftynine patients received prophylactic acyclovir. Forty‐six patients developed ulcerative lesions and 45 of these were culture negative for HSV. Neither the source of transplant (autologous versus allogenic) nor the HSV antibody status of the patient affected the frequency of mucositis. the conditioning regimen appeared to be the most significant factor contributing to the severity of ulcerative mucositis. While the majority of ulcers occurred on movable nonkeratinized mucosa in BMT recipients, the usual sites of reactivation of intraoral HSV are nonmovable, keratinized mucosa. We conclude that HSV is probably not a major etiologic agent of mucositis in BMT recipients and that acyclovir is an effective agent in preventing HSV reactivation.

White-spot Lesions and Gingivitis Microbiotas in Orthodontic Patients:

White-spot lesions (WSL) associated with orthodontic appliances are a cosmetic problem and increase risk for cavities. We characterized the microbiota of WSL, accounting for confounding due to gingivitis. Participants were 60 children with fixed appliances, aged between 10 and 19 yrs, half with WSL. Plaque samples were assayed by a 16S rRNA-based microarray (HOMIM) and by PCR. Mean gingival index was positively associated with WSL (p = 0.018). Taxa associated with WSL by microarray included Granulicatella elegans (p = 0.01), Veillonellaceae sp. HOT 155 (p < 0.01), and Bifidobacterium Cluster 1 (p = 0.11), and by qPCR, Streptococcus mutans (p = 0.008) and Scardovia wiggsiae (p = 0.04) Taxa associated with gingivitis by microarray included: Gemella sanguinis (p = 0.002), Actinomyces sp. HOT 448 (p = 0.003), Prevotella cluster IV (p = 0.021), and Streptococcus sp. HOT 071/070 (p = 0.023); and levels of S. mutans (p = 0.02) and Bifidobacteriaceae (p = 0.012) by qPCR. Species’ associations with WSL were minimally changed with adjustment for gingivitis level. Partial least-squares discriminant analysis yielded good discrimination between children with and those without WSL. Granulicatella, Veillonellaceae and Bifidobacteriaceae, in addition to S. mutans and S. wiggsiae, were associated with the presence of WSL in adolescents undergoing orthodontic treatment. Many taxa showed a stronger association with gingivitis than with WSL.

The oral health of long-term survivors of acute lymphoblastic leukaemia: a comparison of three treatment modalities

Sixty-eight children who were diagnosed with acute lymphoblastic leukaemia (ALL) prior to age 5 years and treated with chemotherapy alone, chemotherapy plus 1800 cGy cranial irradiation (RT), or chemotherapy plus 2400 cGy RT were assessed clinically for overall dental health. All patients were at least 60 months in continuous remission. Dental caries were assessed by NIDR diagnostic criteria, oral hygiene was assessed by the modified Oral Hygiene Index, and gingival health was assessed by the modified gingival index of Loe and Silness. There was no significant difference in caries experience between the three groups nor with the normal population. Those patients that received 2400 cGy RT had significantly higher plaque and periodontal index scores than patients in the other treatment groups. The results of this study suggest that: (1) children with ALL treated with any of the described modalities are at no greater risk of developing dental caries than the normal population; and (2) patients receiving 2400 cGy prior to age 5 years are at greater risk of developing periodontal disease than patients treated with other central nervous system prophylaxis regimens examined in this study.