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Biomedical subjects

D A Hunter

Publications and source records attributed to D A Hunter.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effect of cold preservation on lymphocyte migration into peripheral nerve allografts in sheep.

Lymphocyte migration into fresh and preserved peripheral nerve allografts was quantitated to assess the effect of cold preservation and freeze-thawing pretreatment on the local immunological response to nerve allografts. Out-bred ewes received multiple 1.5-cm subcutaneous heterotopic peroneal nerve autografts, fresh allografts, and pretreated allografts, implanted within the same recipient. Lymphocyte migration was studied at 7 days by injecting autologous 111indium-labeled lymphocytes intravenously. After 3 hr of recirculation, lymphocyte migration into graft tissue was quantitated by a gamma counter (epm/g, mean +/- SEM). Lymphocyte traffic into fresh nerve allografts (21,623 +/- 3783) increased an average 9.4-fold over the autograft value (2918 +/- 377, P < 0.04). Histologic studies illustrated a marked lymphocytic infiltrate of CD4+ and CD8+ cells and enhanced class I and II MHC expression in fresh allografts, but not in autografts. Short-term cold preservation, for 6 and 12 hr (5 degrees C), enhanced lymphocyte entry into pretreated allograft tissue. Conversely, cold preservation for longer periods (1 and 3 weeks) dramatically reduced lymphocyte migration to values below corresponding autograft levels (783 +/- 100 and 1,252 +/- 120, respectively, P < 0.01). A comparable reduction in lymphocyte migration into nerve allografts was observed after freeze-thawing pretreatment (P < 0.01). Cold preservation of donor allogeneic lymphocytes inhibited their capacity to induce intradermal host lymphocyte migration, implicating passenger lymphocytes as a potential cold-sensitive allogeneic component of the nerve allograft. Assessment of the local response to ovine peripheral nerve allografts, utilizing radiolabeled autologous lymphocytes, demonstrated that cold preservation and freeze-thawing pretreatment significantly reduced lymphocyte migration into nerve allografts. The mechanism(s) of reduced lymphocyte migration may involve inactivation or death of antigen-presenting cells, including passenger lymphocytes.

Animals↗
PubMed1993

Comparison of regeneration across nerve allografts with temporary or continuous cyclosporin A immunosuppression.

The efficacy of short-term immunosuppression in a nerve allograft model was examined by comparing regeneration across peripheral nerve allografts with either temporary (12 weeks) or continuous (30 weeks) cyclosporin A treatment. One-hundred fifty Lewis rats received 2-cm nerve grafts from allogeneic ACI or syngeneic Lewis rat donors and were allocated to the following groups: allogeneic grafts and continuous cyclosporin A, with 18 weeks (20 rats) or 30 weeks (20 rats) of survival after graft placement; allogeneic grafts and temporary cyclosporin A, with 12 weeks (10 rats), 18 weeks (20 rats), or 30 weeks (20 rats) of survival; and control rats with allogeneic and syngeneic grafts, no cyclosporin A, with 12, 18, or 30 weeks (10 rats each) of survival. Functional regeneration across the nerve grafts was serially assessed with walking-track analysis. Endpoint evaluations included electrophysiological, histological, and morphometric studies. Both walking-track and electrophysiological function reached a plateau at a significantly worse level in nonimmunosuppressed allograft recipients than in syngeneic or treated allograft recipients. The group with temporary therapy experienced significant worsening in both motor and electrophysiological function at Week 18, 6 weeks after cyclosporin A withdrawal, compared to the group with continuous treatment. At Week 30, motor and electrophysiological function in the temporary-treatment group recovered to levels similar to those of the syngeneic and continuous cyclosporin A groups. Histological assessment of the graft segments from the temporary cyclosporin A group at 18 weeks showed evidence of rejection, with mononuclear cell infiltration and demyelination; morphometric evaluation demonstrated significantly decreased numbers of nerve fibers in the distal host segment. These histological and morphometric changes were no longer present in the nerves from the temporarily immunosuppressed rats at Week 30. Withdrawal of immunosuppression after successful regeneration through nerve allografts results in short-term graft rejection. Eventual restoration of graft histological and function parameters is comparable to continuously immunosuppressed rats. Temporary immunosuppression of nerve allograft recipients is feasible.

Analysis of Variance↗
PubMed1992

Walking track analysis: a long-term assessment of peripheral nerve recovery.

Functional recovery following sciatic, tibial, and peroneal nerve injury was assessed over a 1-year period using walking track analysis in the rat. Internal neurolysis did not affect nerve function. Crush injury induced a temporary, but complete, loss of function that recovered to control levels by 4 weeks. Nerve transection resulted in complete loss of function without any evidence of recovery. After nerve repair, functional recovery occurred, reaching near-optimal recovery by 12 weeks. The degree of functional recovery varied with the specific nerve involved. The sciatic nerve recovered 41 percent of function, whereas the tibial nerve recovered 54 percent of function. The peroneal nerve exhibited the highest degree of recovery, achieving functional levels similar to control values. Assessment of neural regeneration using walking track analysis appears to be a valuable addition to the traditional methods of histology and electrophysiology.

Analysis of Variance↗
PubMed1991

Selective reinnervation: a comparison of recovery following microsuture and conduit nerve repair.

Selective reinnervation was studied by comparing the regeneration across a conventional neurorraphy versus a conduit nerve repair. Lewis rats underwent right sciatic nerve transection followed by one of four different nerve repairs (n = 8/group). In groups I and II a conventional neurorraphy was performed and in groups III and IV the proximal and distal stumps were coapted by use of a silicone conduit with an interstump gap of 5 mm. The proximal and distal stumps in groups I and III were aligned anatomically correct and the proximal stump was rotated 180 degrees in groups II and IV (i.e. proximal peroneal nerve opposite the distal tibial nerve and the proximal tibial nerve opposite the distal peroneal nerve). By 14 weeks, there was an equivalent, but incomplete return in sciatic function index (SFI) in groups I, III, and IV as measured by walking track analysis. However, the SFI became unmeasurable by 6 weeks in all group II animals. At 14 weeks, the percent innervation of the tibialis anterior and medial gastronemius muscles by the peroneal and tibial nerves respectively was estimated by selective compound muscle action potential amplitude recordings. When fascicular alignment was reversed, there was greater tibial (P = 0.02) and lesser peroneal (P = 0.005) innervation of the gastrocnemius muscle in the conduit (group IV) versus the neurorraphy (group II) group. This suggests that the gastrocnemius muscle may be selectively reinnervated by the tibial nerve. However, there was no evidence of selective reinnervation of the tibialis anterior muscle. Despite these differences, the functional recovery in both conduit repair groups (III and IV) was equivalent to a correctly aligned microsuture repair (group I) and superior to that in the incorrectly aligned microsuture repair (group II).

Action Potentials↗
PubMed1991

Inter- and intraobserver reliability of walking-track analysis used to assess sciatic nerve function in rats.

The inter- and intraobserver reliability of the walking-track analysis of sciatic nerve function in the rat was assessed. Twenty-five walking tracks were assessed on three different occasions by four observers. Whereas the interobserver reliability was found to be excellent (r = 0.92), the intraobserver reliability was only satisfactory (r = 0.53 to r = 0.76). Walking-track analysis provides a noninvasive technique to assess function recovery in the rat, with excellent intraobserver reliability demonstrated. The lower intraobserver reliability suggests limitations to this new measurement technique.

Animals↗
PubMed1989

Self-evaluation of walking-track measurement using a Sciatic Function Index.

Recovery of function is of prime importance after peripheral nerve injury and repair. This paper describes a method of obtaining and measuring walking-tracks and generating a Sciatic Function Index (SFI) to quantify functional sciatic nerve recovery in the rat. The reader is provided with a series of walking-tracks to measure, analyze and compare to those analyzed by experienced observers.

Animals↗
PubMed1989

Selection of optimal axon ratio for nerve regeneration.

The traditional teaching that "nerve fibers are lost at the suture line" after a nerve repair was investigated by asking the question, "Can the number of nerve fibers distal to a nerve repair site be increased by increasing the number of nerve fibers proximally?" Ratios of proximal to distal nerve fibers were increased from 1:1 to 2.5:1 to 3.5:1 by suturing peroneal or posterior tibial or sciatic nerve proximally to peroneal nerve distally. At one year following the repair, distal nerve fiber numbers increased to twice normal as the ratio increased to 2.5:1, and then nerve fiber numbers plateaued. Nerve function, as judged by walking track analysis, was best in the peroneal:peroneal group (1:1 ratio), suggesting that appropriateness rather than number of proximal fibers was more critical in this nerve repair model.

Animals↗
PubMed1989

Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat.

Quantification of peripheral nerve regeneration in animal studies of nerve injury and repair by histologic, morphologic, and electrophysiologic parameters has been controversial because such studies may not necessarily correlate with actual nerve function. This study modifies the previously described sciatic functional index (SFI), tibial functional index (TFI), and peroneal functional index (PFI) based on multiple linear regression analysis of factors derived from measurements of walking tracks in rats with defined nerve injuries. The factors that contributed to these formulas were print-length factor (PLF), toe-spread factor (TSF), and intermediary toe-spread factor (ITF). It was shown that animals with selective nerve injuries gave walking tracks that were consistent, predictable, and based on known neuromuscular deficits. The new formula for sciatic functional index was compared with previously described indices. The sciatic functional index, tibial functional index, and peroneal functional index offer the peripheral nerve investigator a noninvasive quantitative assessment of hindlimb motor function in the rat with selective hindlimb nerve injury.

Animals↗
PubMed1988

Comparison of regeneration across a vascularized versus conventional nerve graft: case report.

A histological and functional comparison of regeneration across a vascularized and conventional nerve graft was carried out in a clinical case. The two branches of the medial antebrachial cutaneous nerve were used to neurotize the median nerve at the wrist. The superficial branch of the radial nerve (vascularized nerve graft) and a conventional sural nerve graft were used as the interposition grafts between the two branches of the medial antebrachial cutaneous nerve and the median nerve. This nerve grafting procedure was carried out in two stages. The proximal neurorrhaphy was carried out 7 months prior to the distal nerve repair. Biopsies were taken from the distal portions of the vascularized radial sensory nerve and the conventional sural nerve at the time of the second procedure. Histological evaluation demonstrated superior regeneration across the vascularized nerve graft. Subjectively, the patient described better sensory recovery in the territory innervated by the vascularized nerve graft. Sensory testing in the two territories demonstrated better sensibility in the territory innervated by the vascularized nerve graft.

Adult↗
PubMed1988

An assessment of the effects of internal neurolysis on a chronically compressed rat sciatic nerve.

Chronically compressed nerves were treated with three surgical modalities. Simple decompression was compared to internal neurolysis with and without the addition of extrafascicular steroid. Electrophysiologic, histologic, and morphometric assessments were performed. Compressed control nerves demonstrated changes compatible with severe nerve compression (Wallerian degeneration). With simple decompression, improvement in histologic and electrophysiologic parameters occurred. When internal neurolysis was added to the decompression, further improvement in histologic and electrophysiologic parameters was noted. There was no added improvement with the addition of steroids.

Animals↗
PubMed1988

The peripheral nerve allograft: a dose-response curve in the rat immunosuppressed with cyclosporin A.

The potential use of peripheral nerve allografts would significantly improve the reconstructive potential for patients with major peripheral nerve deficits. This study evaluated the response of the nerve allograft recipient treated with varying dosages of cyclosporin A (CsA) to determine the minimal effective dosage necessary to prevent nerve graft rejection. Lewis rats (RT1l) were the recipients of syngeneic nerve grafts from identical Lewis donors or allogeneic nerve grafts from ACI (RT1a) donors. Nerve grafts were inlaid next to the intact sciatic nerve of the recipient. The immunologic responsiveness of the recipient animal's lymphocytes to a donor-specific antigenic challenge was assessed by the mixed lymphocyte reaction (MLR). In addition, nerve grafts were evaluated histologically. Animals were monitored for cyclosporin A toxicity. It was found that cyclosporin A (5 mg/kg per day) was effective in rendering the recipient animals unresponsive by mixed lymphocyte reaction at 10, 20, and 40 days after engraftment. This dosage was similarly effective in preventing histologic changes characteristic of nerve allograft rejection. This dosage regimen was nontoxic to the animals. Our study ascertained a minimal nontoxic dosage of cyclosporin A that effectively prevented nerve allograft rejection across a major histocompatibility disparity in rats.

Animals↗
PubMed1988

The peripheral nerve allograft: an assessment of regeneration across nerve allografts in rats immunosuppressed with cyclosporin A.

Lewis rats (RT1(1] were the recipients of 3-cm nerve grafts from syngeneic Lewis donors or allogeneic ACI (RT1a) donors. Microneurosurgical repair of the nerve graft to the transected sciatic nerve of the recipient animal was performed with 10-0 epineurial sutures. Recipients were randomly allocated to cyclosporin A (CsA) immunosuppressed or untreated groups. Cyclosporin A was administered in the minimal effective dosage to prevent nerve allograft rejection across this major histocompatibility disparity (5 mg/kg per day). Nerve regeneration across the nerve grafts was assessed by sciatic function index (SFI) and toe spread index (TSI) determinations serially and by electrophysiologic, histologic, and morphologic assessments 14 weeks after engraftment. Sciatic nerve regeneration across allogeneic nerve grafts in cyclosporin A immunosuppressed recipients was significantly superior compared to the untreated controls (p less than 0.008) and not significantly different from that across the syngeneic control animals.

Animals↗
PubMed1987

A model of chronic nerve compression in the rat.

This article describes a model of chronic nerve compression in the rat. The sciatic nerve of adult male Sprague Dawley rats was banded with a 1-cm Silastic tube for varying periods of time. Morphometric analysis, electrodiagnostic studies, and histological evaluation were carried out 3, 5, 8, and 12 months after banding. Histological evaluation at 3 months was normal. At 5 months perineurial thickening was demonstrated. In the periphery of the fascicles, segmental demyelination was noted; central fibers appeared normal. At 8 months there was further epineurial and perineurial thickening. Marked thinning of the myelin was noted in all fibers and evidence of Wallerian degeneration was apparent. Progressive connective tissue and nerve fiber changes were noted at 12 months. Nerve conduction studies after 3 months of compression demonstrated an increase in conduction velocity compared to the normal unbanded control nerves. Progressive slowing of conduction velocity was noted from 5 through 12 months.

Animals↗
PubMed1987

Medial antebrachial cutaneous--lateral femoral cutaneous neurotization in restoration of sensation to pressure-bearing areas in a paraplegic: a four-year follow-up.

Loss of cutaneous sensation predisposes paraplegics to ulceration in pressure-bearing areas. We have previously described a method of restoring sensation to anesthetic trochanteric or ischial areas by neurotizing the cutaneous territory of the lateral femoral cutaneous nerve with the medial antebrachial cutaneous nerve of the forearm. After reinnervation of the anterior skin, a musculocutaneous flap is rotated to the desired anesthetic area. A four-year follow-up evaluation has shown good recovery of the quickly and slowly adapting fiber receptor system, mediated through innervated hair follicles and resulting in excellent protective sensation.

Adult↗
PubMed1987

The peripheral nerve allograft: an assessment of regeneration in the immunosuppressed host.

Regeneration across the nerve allograft in the immunosuppressed host was assessed using electrical and histologic parameters. The Lewis rat (RTIl) served as the recipient animal, and ACI rats (RTIa) provided the donor nerve allografts. Hydrocortisone and azathioprine were used in various dose schedules as the immunosuppressive agents. Animals were immunosuppressed for either 30 or 100 days. Histologic and electrophysiologic measurements of nerve regeneration were assessed at 30, 100, and 180 days. The degree of nerve regeneration was similar in all experimental groups. Short-term, low-dose immunosuppression was as successful as longer-term, higher-dose immunosuppression therapy. The degree of nerve regeneration in all experimental groups was significantly better than that in the fresh, untreated nerve allograft control group (Lewis/ACI) but was not as good as that seen in the autograft control group (Lewis/Lewis).

Animals↗