Melanotic neuroectodermal tumour of infancy: Refining the surgical approach.

Melanotic neuroectodermal tumours of infancy (MNTI) are particularly rare and although predominantly benign, are infiltrative and locally aggressive. Presenting in the first year of life, prompt diagnosis and effective management are critical in minimizing morbidity and the risk of recurrence. A retrospective review of 11 MNTI managed at Great Ormond Street Hospital (GOSH) from 2000 to 2017 was undertaken. Eight tumours presented in the maxilla, two in the skull and one in the mandible. The primary modality of treatment was surgery in 10 cases with one patient receiving neoadjuvant chemotherapy. In spite of microscopically incomplete resection in seven cases, only three recurred. Overall, there was a local recurrence rate of 27% with no distant metastases noted. Disease-free survival was 100% with a follow-up ranging from 0.75 to 17 years (median 5 years). Taking our results in conjunction with the available literature, there is a role for conservative initial surgery of MNTI and this should be coupled with delayed reconstruction and intensive short-term follow-up. We propose an adapted treatment algorithm that aims to balance the risk of recurrence and malignant change with surgical morbidity in an infant population.

Anabolic potential of bone mineral in human periosteal fibroblasts using steroid markers of healing.

A deproteinized natural cancellous bone mineral (B) was studied in a cell culture model for its anabolic potential using two radiolabelled steroid substrates, 14C-testosterone (14C-T) and 14C-4-androstenedione (14C-4-A) independently; in the presence or absence of the anti-androgen finasteride (F) and minocycline (M). Culture medium was assayed for the biologically active metabolite 5 alpha-dihydrotestosterone (DHT) a marker of regenerative potential and wound healing. Confluent monolayer cultures of human periosteal fibroblasts were incubated in Eagle's minimum essential medium with each of the substrates 14C-T and 14C-4-A. Incubations were performed with previously established optimal concentrations of B5 (milligrams/ml), M25 (µg/ml) and F5 (µg/ml) alone and in combination (n=6) for 24h. The eluent was solvent extracted with ethyl acetate (2 ml x 2) and subjected to TLC in a benzene/acetone solvent system (4:1 v/v) for separation of metabolites; they were quantified using a radioisotope scanner. The yield of DHT was increased over controls in response to B and M with both substrates 14C-T and 14C-4-A by 1.7, 1.8-fold and 1.7, 1.6-fold respectively (n=6; p<0.001; one way ANOVA). Combined incubations of B and M resulted in similar yields. F inhibited DHT yields with both radiolabelled substrates by 2-3-fold (n=6; p<0.001) which was overcome by a combined incubation of F+B to values similar to those of controls (p<0.01). Documented pro-anabolic effects of minocycline were applicable as a standard for confirmation of responses to B. Significant increases in yields of DHT in response to B and M with both substrates indicate their anabolic potential in periosteal fibroblasts with implications for wound healing.

Case report: A unique presentation of severe tongue biting in 10 month-old twins with a novel approach to management.

BACKGROUND: Tongue biting in infants has a variety of aetiological factors and is a distressing problem. CASE REPORT: 10 month-old twin boys presented with severe ulceration of the tongue caused by self-mutilation and a maternal family history of this condition. TREATMENT: Thermoplastic splints were used to protect the tongue and facilitate healing, with denture fixative added to aid retention in the mouth. FOLLOW-UP: The twins have been recalled regularly and at their most recent review, two years after initial presentation, one twin did not need a splint at all, and the other suffered only from very occasional episodes of tongue biting. CONCLUSION: A conservative and well-tolerated approach to treatment for such problems is presented.

Effects of alkaline phosphatase and its inhibitor levamisole on the modulation of androgen metabolism by nicotine and minocycline in human gingival and oral periosteal fibroblasts.

UNLABELLED: The aim of this investigation was to establish the implications of nicotine, minocycline, alkaline phosphatase (AP) and its inhibitor levamisole (L) on tissue turnover in human gingival and periosteal fibroblasts (HGF, HPF) using [14C]-testosterone as substrate. Monolayer cultures of HGF and HPF established from four patients were incubated in duplicate with serial and optimal concentrations of nicotine and minocycline, alone and in combination, for 24h in Eagle's MEM, with the substrate [14C]-testosterone. Further experiments were carried out on HPF only, to investigate the effects of alkaline phosphatase (AP) and its inhibitor levamisole (L) on the metabolism of [14C]-testosterone, followed by the effects of L on the modulatory actions of nicotine. The cell-conditioned medium was then solvent-extracted, analysed and quantified for steroid metabolites using a radioisotope scanner. At low concentrations, nicotine stimulated the synthesis of the physiologically active androgen 5alpha-dihydrotestosterone (DHT) from [14C]-testosterone, with inhibition at higher concentrations (n=4; P<0.01). Minocycline stimulated the synthesis of DHT, with decreased yields in the presence of nicotine (n=4; P<0.01), but greater than with nicotine alone. Alkaline phosphatase significantly enhanced the synthesis of androgen metabolites by HPF (n=4; P<0.01), with inhibition in response to L alone and in combination with AP, to less than control values (n=4; P<0.01). L also caused further inhibition in the yields of androgen metabolites when incubated with nicotine, implying that some of the inhibitory effects of nicotine could be due to inhibition of AP activity. CONCLUSION: This investigation has shown that nicotine can inhibit the formation of matrix-stimulatory steroid metabolites in fibroblasts, partly due to inhibition of AP activity. Minocycline is a useful adjunct, in reducing the inhibition of androgen metabolism caused by nicotine.

Phenytoin-mediated androgen metabolism in gingival fibroblasts. Effects of the antiandrogen finasteride and the alkaline phosphatase inhibitor levamisole.

OBJECTIVES: This investigation attempts to identify the role of the alkaline phosphatase inhibitor levamisole (L) and the antiandrogen finasteride (F) on 5alpha-reductase activity in gingival fibroblasts, to elucidate mechanisms for phenytoin-induced gingival overgrowth. MATERIAL AND METHODS: Human gingival fibroblasts were incubated with Eagle's MEM and 14C-testosterone/14C-4-androstenedione as substrates; effective concentrations of phenytoin (Ph), levamisole (L) and finasteride (F), alone and in combinations of (Ph + F) (Ph + L) were added to the incubate. After 24 h, the medium was analysed for steroid metabolites and quantified using a radioisotope scanner. RESULTS: The metabolites isolated were 5alpha-dihydrotestosterone (DHT), 4-androstenedione (4-A) or testosterone (T) from each substrate. With 14C-T as substrate, Ph stimulated DHT synthesis by 1.7-fold, while F and L inhibited this activity by 1.8-fold and 34%, respectively (n = 6; P < 0.001). The combination of Ph + F reduced yields by 2.7-fold compared with Ph alone and Ph + L reduced DHT synthesis by 2.4-fold compared with Ph alone (n = 6; P < 0.001). When 14C-4-androstenedione was used as substrate, similar trends were identified. CONCLUSION: These results suggest that the alkaline phosphatase inhibitor levamisole and the 5alpha-reductase inhibitor finasteride can substantially decrease the yields of DHT in fibroblasts, stimulated by phenytoin. This could be a potential target for reducing the gingival overgrowth caused by phenytoin.

The effects of human mast-cell products and of phenytoin on androgen 5alpha-reductase expression in human gingival fibroblasts.

The aim was to elucidate mechanisms for phenytoin-induced gingival overgrowth, using effects of type 1 human mast cell (HMC-1) supernatant and histamine on the expression of 5alpha-reductase in human gingival fibroblasts (HGF), and the effects of phenytoin on this activity. Duplicate incubations of HGF in Eagle's minimum essential medium (MEM) were performed with [14C] testosterone and serial concentrations of mast-cell histamine (1-100 microgram/ml)/HMC-1 culture supernatant at serial dilutions of 1-100 microl/ml for 24 h. Other experiments employed optimal concentrations of HMC-1 supernatant (10 microl/ml) or histamine (8 microgram/ml) and phenytoin (1 and 5 microgram/ml), alone and in combination, using two androgen substrates, [14C] testosterone and [14C] 4-androstenedione. At the end of a 24-h incubation the medium was solvent-extracted for steroid metabolites, analysed and quantified in a radioisotope scanner. HMC-1, histamine (n=3) and phenytoin (n=6) significantly increased the synthesis of dihydrotestosterone and 4-androstenedione by up to 80% (P<0.01); the combination of HMC-1 and phenytoin caused two-fold increases (n=6; P<0.01). The incubations with histamine alone and in combination with phenytoin showed significant stimulation of dihydroxytestosterone and the diols alone and in combination, which was less pronounced in combination. This investigation demonstrates significant stimulation of 5alpha-reductase activity in human gingival fibroblasts by mast-cell supernatant and a specific product histamine, alone and in combination with phenytoin. Androgen 5alpha-reductase-mediated anabolic actions in connective tissue are well documented. The findings suggest a novel hypothesis that mast-cell mediated androgen action in the gingiva in response to phenytoin could contribute to gingival overgrowth.

Noise level evaluation of dental handpieces.

We evaluated the noise level of fourteen air-driven handpieces, six low speed (less than 20,000 rev/min) and eight high speed (greater than 160,000 rev/min), with respect to a three-directional co-ordinate system and distances of 6, 12 and 18 in. in each chosen direction. A two-way analysis of variance of the noise level between handpieces and positions indicates that large significant differences exist amongst handpieces and in different positions, and that interaction is just barely significant. The ranking and least significant differences for the mean of all handpieces v. position and for the mean of all positions v. handpiece were compared with the results for the ranking and significances from the one-way ANOVAS for each handpiece v. position and for each position v. handpiece. A trend exists with some of the handpieces of straight design (all low speed) for increased noise levels in a direction perpendicular to the handpieces and decreased levels in a direction parallel to the handpieces. For handpieces of angled design (all high speed) both directions parallel and perpendicular (the perpendicular to the longitudinal turbine axis) to the rotor axis indicate increased noise levels. The parallel direction includes the exiting air from the exhaust port. The perpendicular direction can be indicative of an aerodynamic factor associated with the established air flow patterns. The extremes in noise level were 56.8 dBA for a low-speed handpiece of straight design at the 18 in. distance in a direction parallel to the handpiece, and 87.3 dBA for a high speed handpiece at the 6 in. distance in a perpendicular direction.