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Biomedical subjects

S E Mackinnon

Publications and source records attributed to S E Mackinnon.

At least 19 recordsLinked to original sources
PubMed2002

Patient outcome following a thoracodorsal to musculocutaneous nerve transfer for reconstruction of elbow flexion.

This study reports patient outcome following a thoracodorsal to musculocutaneous nerve transfer. We retrospectively reviewed the charts of six patients who had undergone transfer of the thoracodorsal nerve to the musculocutaneous nerve for reconstruction of elbow flexion. The mean age was 47 years (standard deviation: 24 years; range: 17-72 years). The mean time from injury to surgery was 3 months (standard deviation: 2 months; range: 1-5 months). In all cases, the biceps muscle was successfully reinnervated; in one case the Medical Research Council (MRC) muscle grade was grade 5, in four cases it was grade 4, and in one case it was grade 2. No patients complained of functional weakness with shoulder adduction and/or internal rotation. In the majority of cases, transfer of the thoracodorsal nerve to the musculocutaneous nerve provides excellent recovery of elbow flexion.

Adolescent↗
PubMed2002

End-to-side neurorrhaphy and lateral axonal sprouting in a long graft rat model.

OBJECTIVE/HYPOTHESIS: Controversy exists regarding collateral axonal sprouting across an end-to-side neurorrhaphy to provide functional motor reinnervation of a target organ without compromise of the donor nerve. Rat models may be limited in the study of end-to-side repair given potential contamination from the proximal nerve stump of the recipient distal nerve and the use of antagonistic muscle groups for donor and recipient. The current study attempts to address these issues by using a rat model in which an end-to-side coaptation is performed with a long graft interposed between the intact donor tibial nerve and the divided, distal contralateral tibial nerve. MATERIALS AND METHODS: The graft used in proximal end-to-side coaptation consisted of both sciatic nerves in a donor syngeneic animal. The distal repair to the contralateral tibial nerve was done immediately or in a delayed fashion to allow potential motor axons to transverse the graft before division of the recipient tibial nerve. RESULTS: After 24 weeks, axons were noted to transverse the entire distance of the graft and into the contralateral distal posterior tibial nerve. A significant increase in axonal numbers was observed in the immediate repairs compared with the delayed. No animal recovered functional motor ability on the contralateral side as assessed by walking tracks. CONCLUSIONS: These findings suggest the importance of immediate distal neurotrophic factors in encouraging nerve regeneration even in a long graft end-to-side repair. Our model is successful in demonstrating innervation through an end-to-side coaptation but questions its use given the lack of motor recovery.

Animals↗
PubMed2001

Development of the blood-nerve barrier in neonatal rats.

The blood-nerve barrier (BNB) is constituted by the perineurium and the endothelium of endoneurial microvessels. We investigated the age at which the vascular component of BNB function is established in the rat and the ultrastructural modifications accompanying changes in permeability. BNB permeability was assessed with injections of Evans blue albumin (EBA) and horseradish peroxidase (HRP) in rats of different ages. Sciatic nerve sections were studied using fluorescence and electron microscopy. Nerves from animals injected with EBA indicated that the BNB is not functional before 13 days of life but that its function is established by 16 days. These results were confirmed by electron microscope examination of nerve sections from animals injected with HRP, which showed clefts between the endothelial cells of endoneurial vessels in young rats. In rats over 18 days, these clefts were occluded by tight junctions, which prevented HRP from leaving the vessel lumen and conferred BNB function. Systematic morphometric analysis of nerves from different age groups allowed the establishment of baseline normal histologic neural development with age.

Animals↗
PubMed2001

A subcutaneous heterotopic limb transplantation model in the mouse for prolonged allograft survival.

A heterotopic position of a limb allograft is advantageous in the fragile mouse model to reduce mortality but is prone to autotomy. The purpose of this study was to describe a new heterotopic limb transplantation model in the mouse for prolonged allograft survival. Eleven lower hindlimbs were transplanted in a heterotopic subcutaneous position in the groin of the recipient animal with the donor skin inset as a skin paddle for monitoring. Seven transplants were syngeneic (Balb/c) and four were allogeneic (C57Bl/6 donor). The overall success rate (acute survival < 7 days) was 73% (8/11) and the mortality rate was 18% (2/11). Five of seven syngeneic transplants survived for 60 days and were harvested for histology. Recipients of successful allogeneic transplants (n = 3) received no immunosuppression and rejected their allografts between 8 and 11 days postoperatively. Mixed lymphocyte culture and flow cytometry demonstrated secondary immune responses by pre-sensitized animals, and histology showed lymphocytic infiltration and necrosis consistent with acute rejection.

Animals↗
PubMed2001

Secondary carpal tunnel surgery.

A small but significant group of patients with carpal tunnel syndrome "fail" primary carpal tunnel release and require secondary surgery. The persistence or recurrence of previous symptoms or the development of new symptoms is often indicative of the nature of the patient's problem. Postoperative complications may be classified into the general areas of neurological, vascular, tendon, and wrist complaints. A thorough clinical evaluation, including a complete neurological examination of the hand and upper extremity, provides an accurate assessment of the status of the median nerve. Important surgical techniques that may be used during secondary carpal tunnel surgery include internal neurolysis, neuroma-in-continuity assessment, neuroma management, nerve grafting, and tissue interposition flaps.

Carpal Tunnel Syndrome↗
PubMed2001

Flexor digitorum superficialis nerve transfer to restore pronation: two case reports and anatomic study.

Loss of pronation affects most activities of daily living. We report 2 cases of traumatic loss of pronator teres function and successful reconstruction by transfer of a redundant motor branch to the flexor digitorum superficialis to the pronator teres branch(es). Follow-up period was 2 years and pronation strength was restored to +4/5 and 5/5 in the 2 patients. The anatomy of the median nerve in the proximal forearm was examined by dissecting 31 cadaver specimens. A branching scheme was formulated. The histomorphometric properties of the individual muscular branches were studied in 15 fresh specimens to evaluate their suitability and size match for nerve transfer.

Accidents, Traffic↗
PubMed2001

Rat-strain differences in recovery following peripheral-nerve allotransplantation.

The rat model is commonly utilized in peripheral nerve research. Due to the short length of the rat limb and the animal's inherent neuroregenerative capacity, the timing of assessment of nerve regeneration is critical, and significant differences between groups can be lost if assessment is done too late. Additionally, the comparison of data from different rat-strain combinations has been questioned. This study better defines the time course of recovery after peripheral nerve grafting, and examines differences between Buffalo (BUF), Lewis (LEW), and ACI rats. Tibial-nerve isografts and allografts were performed and harvested at 6, 8, 10, or 14 weeks. Histomorphometry documented a statistically significant difference in the ACI/LEW and LEW/LEW combination at 10 weeks. No strain differences in graft rejection were noted. The optimal time to assess for histomorphometric differences in the ACI/LEW and LEW/LEW combination is at 10 weeks postoperatively.

Animals↗
PubMed2001

Development of a mouse model for heterotopic limb and composite-tissue transplantation.

The mouse remains the most suitable model to study the complexities of the immune system and transplant rejection. The purpose of this study was to describe a new mouse model for heterotopic limb and composite tissue transplantation. Eighteen procedures were performed, including 10 heterotopic lower hind limb, four vascularized skin, and four vascularized muscle transplantations. Three transplants were allogeneic, and the rest were syngeneic. All successful syngeneic transplants were harvested at 11 days postoperatively, except for one skin and one limb transplant that were followed for over 30 days. The allogeneic transplants showed signs of rejection between 7 to 11 days postoperatively. Results of mixed lymphocyte culture (p < 0.05) and histology evaluations from the allogeneic recipients were consistent with acute rejection as the cause of allograft loss. The mortality rate was 16.7 percent, and the overall success rate was 72.2 percent. Details of the operative procedure are described, and important technical factors are discussed.

Animals↗
PubMed2001

Portal venous ultraviolet B-irradiated donor alloantigen prevents rejection in circumferential rat tracheal allografts.

BACKGROUND: Before tracheal transplantation can be considered as a method of reconstruction in patients with extensive circumferential tracheal defects, we must achieve a state of nontoxic, donor-specific tolerance so that the risks of such a transplant do not outweigh the benefits. OBJECTIVE: Our objective was to determine whether a single intraportal injection of modified donor alloantigen achieves donor-specific immunosuppression for major histocompatibility complex-mismatched rat tracheal allografts. STUDY DESIGN: Buffalo (recipient) rats were pretreated with either a single portal-vein administration of ultraviolet B (UVB)-irradiated donor splenocytes (n = 4) or an intraportal inoculation of nonirradiated donor splenocytes (n = 4). Major histocompatibility complex-mismatched Lewis (donor) tracheal allograft segments were then grafted into treatment groups 7 days after donor-cell pretreatment. Tracheal rejection was assessed by histologic analysis, mucosal cilia motility, and in vitro immunologic assessment. RESULTS: The UVB-treated group demonstrated no acute or chronic rejection as well as complete functional recovery. In vitro immunologic assessment demonstrated a donor-specific hyporesponsiveness and donor allospecificity. Untreated animals and those receiving nonirradiated donor splenocytes showed acute rejection of their tracheal allografts. CONCLUSION: Recipient pretreatment with intraportally administered UVB-irradiated donor splenocytes prevents rejection of circumferential rat tracheal allograft segments by inducing a donor-specific immune hyporesponsiveness.

Animals↗
PubMed2001

FK506 rescues peripheral nerve allografts in acute rejection.

This study investigated the ability of the immunosuppressant FK506 to reverse nerve allograft rejection in progress. Eighty-four Buffalo rats received posterior tibial nerve grafts from either Lewis or Buffalo donor animals. Allografts were left untreated for either 7, 10, or 14 days before receiving daily subcutaneous FK506 injections (2 mg/kg). Time-matched control animals received either an isograft, an allograft with continuous FK506, or an allograft with no postoperative FK506 therapy. All animals underwent weekly evaluation of nerve function by walking track analysis. Experimental group animals were sacrificed either immediately prior to initiation of FK506 therapy (days 7, 10, or 14), after 2 weeks of immunosuppressive treatment, or 8 weeks postsurgery. Histomorphometric analysis, consisting of measurements of total number of nerve fibers, neural density, and percent of neural debris, demonstrated a statistically significant increase in regeneration in the isograft group relative to the untreated allograft group within 28 days of transplantation. Grafts harvested from animals receiving 2 weeks of FK506 after 7 or 10 days of rejection were histomorphometrically similar to time-matched isografts. By contrast, grafts from animals receiving 2 weeks of FK506 following 14 days without therapy resembled untreated allografts and demonstrated significant histomorphometric differences from isografts at the corresponding time point. Analysis of walking track data confirmed that relative to untreated allografts, functional recovery was hastened in animals receiving an isograft, or allograft treated with FK506. This study demonstrated that when started within 10 days of graft placement, FK506 could reverse nerve allograft rejection in rats evaluated following 2 weeks of treatment.

Acute Disease↗
PubMed2001

Pretreatment with portal venous ultraviolet B-irradiated donor alloantigen promotes donor-specific tolerance to rat nerve allografts.

OBJECTIVE: To determine if a single intraportal inoculation of ultraviolet B-irradiated (UVB) donor splenocytes can prevent nerve allograft rejection and confer donor-specific immunotolerance to rat nerve allograft segments. METHODS: Age-matched, class I and class II major histocompatibility complex (MHC) mismatched Buffalo (RT1b) rats were transplanted with a syngeneic nerve isograft, a Lewis (RT1l) nerve allograft, or a Brown-Norway (RT1n) rat nerve allograft segment. Control Buffalo rats in group I received a 3.0-cm Lewis (RT11) sciatic-posterior tibial interposition nerve allograft without pretreatment; group II Buffalo rats received a syngeneic Buffalo nerve isograft without pretreatment. Group III Buffalo recipients were inoculated with 2.5 x 107 UVB-irradiated Lewis donor splenocyte cells by portal venous administration 7 days before transplantation with a 3.0-cm sciatic-posterior tibial nerve allograft from a Lewis (RT11) or a third party Brown-Norway rat (RT1n) donor (group IV). Nerve graft regeneration was assessed with walking track analysis, nerve conduction studies, retrograde neural tracing, nerve graft histology, and morphometry. Recipient immune tolerance was assessed through in vitro immunological assessment. RESULTS: Pretreatment with UVB-irradiated donor splenocytes 7 days before transplantation prevented nerve allograft rejection. Pretreated animals receiving a nerve allograft recovered limb function, and demonstrated morphological, histological, and electrophysiologic parameters of nerve regeneration similar to that measured in rats receiving a nerve isograft. In vitro immunological assessment by mixed lymphocyte culture (MLC), cytotoxic T lymphocyte (CTL) assay, limiting dilution analysis (LDA) of helper (pTH) and cytotoxic (pCTL) precursor frequencies, and IL-2 production demonstrated a marked donor-specific suppression in allografted animals pretreated with intraportal UVB-irradiated donor splenocytes. These assessments correlated with indefinite acceptance of donor nerve allografts. CONCLUSIONS: A single pretreatment with a single intraportal dose of UVB-modified donor antigen specifically induces tolerance to peripheral nerve allografts in rats.

Animals↗
PubMed2001

Clinical outcome following nerve allograft transplantation.

The clinical outcome of seven patients who underwent reconstruction of long upper- and lower-extremity peripheral nerve gaps with interposition peripheral nerve allografts is reported. Patients were selected for transplantation when the nerve gaps exceeded the length that could be reconstructed with available autograft tissue. Before transplantation, cadaveric allografts were harvested and preserved for 7 days in University of Wisconsin Cold Storage Solution at 5 degrees C. In the interim, patients were started on an immunosuppressive regimen consisting of either cyclosporin A or tacrolimus (FK506), azathioprine, and prednisone. Immunosuppression was discontinued 6 months after regeneration across the allograft(s) was evident. Six patients demonstrated return of motor function and sensation in the affected limb, and one patient experienced rejection of the allograft secondary to subtherapeutic immunosuppression. In addition to providing the ability to restore nerve continuity in severe extremity injuries, successful nerve allografting protocols have direct applicability to composite tissue transplantation.

Adolescent↗
PubMed2001

Current approach to cubital tunnel syndrome.

The choice for surgical treatment of cubital tunnel syndrome is no clearer today than when it was reviewed 10 years ago. There continue to be no significant prospective randomized trials to adequately compare the different surgical techniques. Even if such a trial were performed, most hand surgeons would probably continue to be skeptical. In the end, each surgeon must rely on his or her own personal experience or judgment. Based on the authors' experience in the treatment of cubital tunnel syndrome, they are confident that anterior transmuscular transposition of the ulnar nerve obtains the best results when the preoperative algorithm is properly applied and early postoperative physical therapy is instituted.

Algorithms↗
PubMed2000

FK506 promotes functional recovery in crushed rat sciatic nerve.

In this study we examine whether the systemic administration of FK506 or Cyclosporin A (CsA) expedited functional recovery following an axonotmetic nerve injury, and compared their effects in a rat model. Seventy-five adult Buffalo rats received a crush injury to the right posterior tibial nerve and subsequently underwent either no treatment (group I), daily injections of FK506 (group II), or daily injections of CsA (group III). Walking track analysis demonstrated return of hindlimb function by 20 days postoperatively in group I, 14 days in group II, and 18 days in group III. The blood-nerve barrier (BNB) was reconstituted by postoperative day (POD) 7 in both FK506- and CsA-treated animals and by POD 13 in control animals. These results suggest that recovery of function is more rapid with daily administration of FK506 than with CsA or no treatment, perhaps because of earlier restoration of the blood-nerve barrier. Agents that facilitate nerve regeneration have the potential to limit the extent of motor endplate loss and muscle atrophy seen with prolonged denervation, thereby limiting permanent functional loss.

Analysis of Variance↗
PubMed2000

Long nerve allografts in sheep with Cyclosporin A immunosuppression.

Rodent studies of nerve allografts are limited by a relatively short length of graft segment. The authors attempted to establish an outbred sheep model that would allow the study of longer, more clinically relevant nerve gaps. Using outbred ewes, two 8-cm long radial sensory nerves were grafted into gaps (5 cm) in the median nerve. Sheep received an autograft and an allograft. Four sheep were immunosuppressed with Cyclosporin A (CsA) and four were controls. Blood CsA levels greater than 1000 microg/L were obtained. Systemic immunosuppression resulted in severe opportunistic infections, and the sheep were sacrificed between 35 and 47 days following surgery. Histologically, in the autografts and CsA-treated allografts, evidence of nerve regeneration was seen. Non-immunosuppressed allografts were clearly rejected. While clear differences in the histology of experimental and control grafted nerve tissues were seen, the sheep allograft model presents considerable challenges due to immunosuppression-related infectious complications.

Animals↗
PubMed2000

Effects of FKBP-12 ligands following tibial nerve injury in rats.

The neuroregenerative properties of FK506, an FKBP-12 ligand that inhibits calcineurin, and V-10,367, an FKBP-12 ligand that does not inhibit calcineurin, were evaluated in crush and transection models. Rats were randomly assigned to one of seven groups, including untreated controls and FK506- or V-10,367-treated experimental groups. Following crush or transection nerve injury, animals were assessed with walking tracks, and histomorphometry. FK506-treated animals demonstrated significant functional recovery 11 days following crush and 18 days following transection injury. In untreated and V-10,367 treated animals, nerves recovered 13 days following crush injury, but did not improve significantly prior to sacrifice at 28 days in animals sustaining a transection injury. No statistically significant differences in histomorphometric parameters were identified between any of the groups. The study confirms that FK506 accelerates recovery from tibial nerve injury.

Animals↗
PubMed2000

Outcome following implantation of a peripheral nerve stimulator in patients with chronic nerve pain.

This study evaluated the usefulness of the implanted peripheral nerve stimulator in patients with pain following injury to a peripheral nerve. The patient sample (n = 17) consisted of 7 men and 10 women with a mean age of 48 years (SD = 18 years). The mean follow-up time since implantation of the stimulator was 21 months (SD = 15 months). Workers' compensation and/or litigation were involved in 11 cases. Peripheral nerve stimulators were placed in the upper extremity in 12 patients and in the lower extremity in 5 patients. Pain relief following implantation was rated as excellent by five patients, good by six patients, fair by four patients, and poor by two patients. A statistically significant decrease in reported pain level was found postoperatively (p < 0.0003). There was no statistically significant difference in postoperative pain level between men and women (p = 0.30), between cases involving workers' compensation or litigation and those not involving these issues (p = 1.0), or between patients who received an upper-extremity implant and those who received a lower-extremity implant (p = 0.56). Of the 12 patients who were unable to work before the operation, 6 returned to work after the operation. In conclusion, peripheral nerve stimulators can be useful in decreasing pain in carefully selected patients with severe neurogenic pain.

Adolescent↗