Simon Atkins

Interleukin-10 reduces scarring and enhances regeneration at a site of sciatic nerve repair.

Abstract  Axonal regeneration at a site of peripheral nerve repair can be impeded by the formation of scar tissue, which creates a mechanical barrier and initiates the development of multiple branched axonal sprouts that form a neuroma. We have investigated the hypothesis that the application of a scar‐reducing agent to the nerve repair site would permit better axonal regeneration. In anaesthetised C57 Black‐6 mice, the left sciatic nerve was sectioned and immediately re‐approximated using four epineurial sutures. In five groups of eight mice, we injected transforming growth factor‐β3 (50 or 500 ng), interleukin‐10 (IL‐10) (125 or 500 ng), or saline into and around the repair site, both before and after the nerve section. Another group of eight animals acted as sham‐operated controls. After 6 weeks, the outcome was assessed by recording compound action potentials (CAPs), measuring collagen levels using picrosirius red staining, and counting the number of myelinated axons proximal and distal to the repair. CAPs evoked by electrical stimulation distal to the repair were significantly smaller in all repair groups except for the low‐dose IL‐10 group, where they were not significantly different from that in controls. The area of staining for collagen had significantly increased in all repair groups except for the low‐dose IL‐10 group, which was not significantly different from that in controls. The myelinated fibre counts were always higher distal to the repair site, but there were no significant differences between groups. We conclude that administration of a low‐dose of IL‐10 to a site of sciatic nerve repair reduces scar formation and permits better regeneration of the damaged axons.

The effect of Mannose-6-Phosphate on recovery after sciatic nerve repair.

We have determined the effect of applying Mannose-6-Phosphate (M6P), a scar reducing agent, to a site of sciatic nerve repair. In anaesthetised C57-Black-6 mice, the left sciatic nerve was sectioned and repaired using 4 epineurial sutures. Either 100 μl of 600 mM Mannose-6-Phosphate (29 animals), or 100 μl of phosphate buffered saline as a placebo control (29 animals), was injected into and around the nerve repair site. A further group acted as sham-operated controls. After 6 or 12 weeks of recovery the extent of regeneration was assessed electrophysiologically and the percentage area of collagen staining at the repair site was analysed using picrosirius red and image analysis. Gait analysis was undertaken pre-operatively and at 1, 3, 6, 9 and 12 weeks postoperatively, to assess functional recovery. At 6 weeks the compound action potentials recorded from the regenerated nerves in the M6P group were significantly larger than in the placebo controls (P=0.015), and the conduction velocities were significantly faster (P=0.005), but there were no significant differences between these groups at 12 weeks. Gait analysis suggested better early functional recovery in the M6P group. In both repair groups there was a significant reduction in collagen staining between 6 and 12 weeks, suggestive of scar remodelling. We conclude that the normal scar remodelling process aids long term recovery in repaired nerves. Administration of 600 mM M6P to the nerve repair site enhances nerve regeneration and functional recovery in the early stages, and may lead to improved outcomes.

A comparison between the effects of three potential scar-reducing agents applied at a site of sciatic nerve repair

We have investigated the effect of three potential scar-reducing agents applied at a sciatic nerve repair site in C57-black-6 mice. Under anaesthesia the nerve was transected, repaired using four epineurial sutures, and 100 μl of either triamcinolone acetonide (1 mg/100 μl), an interleukin-10 peptide fragment (125 ng/100 μl or 500 ng/100 μl) or mannose-6-phosphate (M6P, 200 mM or 600 mM) was injected into and around the nerve. After 6 weeks the extent of regeneration was assessed electrophysiologically by determining the ratio of the compound action potential (CAP) modulus evoked by electrical stimulation of the nerve 2 mm distal or proximal to the repair site. The conduction velocity of the fastest components in the CAP was also calculated. The percentage area of collagen staining (PAS) at the repair site was analysed using Picrosirius Red and image analysis. Comparisons were made with a placebo group (100 μl of phosphate buffered saline) and sham-operated controls. The median CAP modulus ratio in the 600 mM M6P group was 0.44, which was significantly higher than in the placebo group (0.24, P=0.012: Kruskal-Wallis test). Conduction velocities were also faster in the 600 mM M6P group (median 30 m s(-1)) than in the placebo group (median 27.8 m s(-1); P=0.0197: Kruskal-Wallis test). None of the other treated groups were significantly different from the placebo, and all had significantly lower CAP ratios than the sham controls (P<0.05). All repair groups had a significantly higher PAS for collagen than sham controls. We conclude that the administration of 600 mM mannose-6-phosphate to a nerve repair site enhances axonal regeneration.

Treatment of the edentulous atrophic maxilla using zygomatic implants: evaluation of survival rates over 5–10 years

The aim of this retrospective observational cohort study was to analyse and report the 5-10-year survival rates of endosseous zygomatic implants used in the rehabilitation of the atrophic maxilla. Forty-three consecutive zygomatic implant placements in 25 patients were evaluated over a 5-10-year period. All zygomatic implant surgery was carried out under general anaesthesia. Nobel Biocare zygomatic machined-surface implants were used, and placement was undertaken using the modified sinus slot method. The main outcome measures and determinants for success were survival of the restored implants and the proportion of originally planned prostheses delivered to patients. Of the 25 patients treated, 12 were male and 13 were female; 19 were non-smokers, and the mean age at time of surgery was 64 years. Patients were treatment-planned for implant-retained bridgework, a removable prosthesis retained by fixed cast gold or milled titanium beams, or magnet-retained removable prostheses. A combination of zygomatic and conventional implants was used in all but one patient. In this study it was shown that the overall success rate for zygomatic implants was 86%, with six of the implants either failing to integrate or requiring removal due to persistent infection associated with the maxillary sinus. All patients received their planned prosthesis, although in six cases the method of retention required modification. This study illustrates that zygomatic implants are a successful and important treatment option when trying to restore the atrophic maxilla, with the potential to avoid additional augmentation/grafting procedures and resulting in a high long-term success rate.

Sublingual dermoid cysts: case report and review of the literature

BACKGROUND Dermoid cysts in the floor of the mouth are relatively uncommon developmental lesions. They are thought to arise in the midline and along the lines of embryonic fusion of the facial processes containing ectodermal tissue. CASE REPORT A 17-year-old female presented with a 3-month history of a growing, progressive swelling in the mouth floor. Clinical examination revealed a rather large symmetrical, soft swelling in the mouth floor, displacing the tongue superiorly. The fast growing nature and size of the lesion raised suspicion of potential compromise to the airway. Surgical excision was therefore performed. CONCLUSION Differential diagnosis of cystic lesions in the floor of the mouth is of paramount importance, as the recommended surgical techniques vary depending on the anatomical position of the lesions. The intraoral approach is preferred for those lesions that do not extend beyond the mylohyoid muscle boundaries; this leads to a satisfactory cosmetic and functional outcome.

Histomorphometric changes in repaired mouse sciatic nerves are unaffected by the application of a scar-reducing agent

Microsurgical repair of transected peripheral nerves is compromised by the formation of scar tissue and the development of a neuroma, thereby limiting the success of regeneration. The aim of this study was to quantify histomorphometrically the structural changes in neural tissue that result from repair, and determine the effect of mannose‐6‐phosphate (M6P), a scar‐reducing agent previously shown to enhance regeneration. In anaesthetised C57‐black‐6 mice, the left sciatic nerve was sectioned and repaired using four epineurial sutures. Either 100 μL of 600 mm M6P (five animals) or 100 μL of phosphate‐buffered saline (placebo controls, five animals) was injected into and around the nerve repair site. A further group acted as sham‐operated controls. After recovery for 6 weeks, the nerve was harvested for analysis using light and electron microscopy. Analysis revealed that when compared with sham controls, myelinated axons had smaller diameters both proximal and distal to the repair. Myelinated axon counts, axonal density and size all decreased across the repair site. There were normal numbers and densities of non‐myelinated axons both proximal and distal to the repair. However, there were more Remak bundles distal to the repair site, and fewer non‐myelinated axons per Remak bundle. Application of M6P did not affect any of these parameters.