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Biomedical subjects

I H Whitworth

Publications and source records attributed to I H Whitworth.

8 recordsLinked to original sources

Nerve growth factor enhances nerve regeneration through fibronectin grafts.

Soluble fibronectin and nerve growth factor (NGF) promote axonal regeneration when placed in silicone tubes. We investigated the ability of orientated fibronectin mats to bind and release bioactive NGF and the possibility of augmenting axonal regeneration following axotomy by using fibronectin conduits impregnated with NGF. The release of NGF was quantified using a fluorometric ELISA and bioactivity confirmed with a neuronal culture bioassay. Immunohistochemical techniques and computerized image analysis were used to assess the rate and volume of axonal and Schwann cell regeneration. The delivery of NGF to the site of injury produced an increase in the rate (P < or = 0.007) and volume (P < or = 0.004) of both axonal and Schwann cell regeneration when compared to conduits of plain fibronectin. We conclude that the local delivery of NGF by impregnated fibronectin conduits enhances axonal regeneration.

Animals↗

Targeted delivery of nerve growth factor via fibronectin conduits assists nerve regeneration in control and diabetic rats.

This study examined the influence of fibronectin conduits joining two halves of a sectioned sciatic nerve, with and without preimpregnation with nerve growth factor, on regeneration in rats with streptozotocin-induced diabetes mellitus. Regeneration, measured morphometrically in fibres containing immunoreactivity to calcitonin gene-related peptide (CGRP) and GAP-43, was significantly less (P < 0.0001 for all comparisons) in diabetic rats with fibronectin mat grafts without nerve growth factor compared to similarly treated controls. Regeneration distances in diabetic rats were reduced to 43% (CGRP-reactive fibres) and 44% (GAP-43-reactive fibres) of controls, and the total amounts of immunoreactivities in the conduits were also reduced, though by lesser amounts (55 and 61% of controls respectively). Impregnation of the conduits with nerve growth factor before implantation increased the distance and amounts of regenerating immunoreactivity in both control and diabetic rats for both CGRP and GAP-43, such that these regeneration parameters were similar in nerve growth factor-treated diabetic rats to those in control rats implanted with untreated fibronectin mat conduits. These findings implicate impaired neurotrophic support in the defective regeneration characteristic of diabetic. neuropathy.

Animals↗

Increased axonal regeneration over long nerve gaps using autologous nerve-muscle sandwich grafts.

Poor recovery is seen after repair of long defects in peripheral nerves when denatured muscle grafts or regeneration chambers providing physical support alone are used. The presence of Schwann cells and neurotrophic factors is required for axons to migrate significant distances. In this study we have used immunohistochemical techniques and axon counts to quantify the regeneration seen when 5 cm defects in rabbit sciatic nerve were repaired with a composite graft consisting of 2-3 mm lengths of fresh autologous nerve sandwiched between 1 cm frozen-thawed muscle grafts. This technique led to a similar pattern of regeneration as that seen in autologous nerve grafts, used as controls, and a significantly (P < 0.0001) greater axonal and Schwann cell regeneration compared with that seen in frozen-thawed muscle grafts of the same total length. In conclusion, we present a simple technique for incorporating a depot of Schwann cells and other essential components into a nerve conduit which has a marked effect on axonal regeneration across long defects.

Animals↗

Different muscle graft denaturing methods and their use for nerve repair.

In an attempt to enhance recovery through denatured muscle grafts we have used different methods to denature muscle, either using dry heat in a microwave oven or by warming in sterile distilled water. Axonal regeneration was studied at intervals from day 5 to day 60 after insertion of the muscle grafts and compared to results found in frozen-thawed muscle grafts and in autologous nerve grafts used as controls. Axonal regeneration, Schwann cell behaviour and the degree of inflammation were quantified using immunohistochemical techniques and computerised image analysis. Autologous nerve grafts supported the highest rates and volumes of axonal regeneration until day 30 when the microwaved muscle grafts had the highest values for axonal immunostaining and at 60 days the highest level of Schwann cell immunoreactivity. We conclude that microwave heating is suitable as an alternative denaturing method for successful muscle grafts and has a potential clinical use.

Animals↗

Orientated mats of fibronectin as a conduit material for use in peripheral nerve repair.

This study introduces a new nerve conduit material consisting of orientated strands of the cell adhesive fibronectin. Axonal regeneration, Schwann cell behaviour and the degree of inflammation were quantified using immunohistochemical techniques and computerized image analysis. The results when fibronectin was used to bridge a 1 cm defect in rat sciatic nerve were compared to those with autologous nerve grafts and freeze-thawed muscle grafts used as controls. The nerve grafts supported the highest rate and amount of axonal regeneration in the first 10 days; however, the fibronectin supported a significantly faster rate of growth (P = 0.0008) and amount (P = 0.0001) of axons than the freeze-thawed muscle grafts. From day 15 onwards, the fibronectin and nerve grafts had comparable amounts of regenerating axons and Schwann cells. We conclude that the orientated form of fibronectin is a suitable material for successful nerve repair and has potential clinical use.

Analysis of Variance↗

Neck swellings which mimic branchial cysts in HIV-positive patients.

A retrospective review of over 700 HIV-positive patients referred to the ENT department at St Mary's Hospital was undertaken. This revealed nine patients whose initial presentation was due to an upper neck swelling. The clinical and cytological results are discussed as well as consideration of the similarity of these lesions to branchial cysts, and the implication of the involvement of lymphoid tissue in the aetiology of branchial cysts. With the increasing incidence of HIV infection it is important that patients with these lesions are investigated appropriately before any surgery is contemplated.

Adult↗