Search PubMed⌕ Search

Biomedical subjects

Susan E Mackinnon

Publications and source records attributed to Susan E Mackinnon.

At least 73 records · Page 4Linked to original sources
PubMed2003

Dose-dependent effects of FK506 on neuroregeneration in a rat model.

This study explored the effects of different doses of FK506 on peripheral nerve regeneration, to determine whether neuroregeneration could be enhanced without the toxicity of systemic immunosuppression. In the first part of the study, subimmunosuppressive doses of FK506 were determined by examining skin allograft survival in a rat model. Full-thickness skin grafts (2 cm2) from Wistar rats were grafted to recipient Lewis rats. The procedure was performed for six groups (n = 6). The control group received no FK506, and the other five groups received daily doses of FK506 of 0.125, 0.25, 0.5, 1.0, or 2.0 mg/kg. Animals that received 2.0 mg/kg FK506 per day exhibited complete skin graft take, whereas all other groups demonstrated complete rejection. After determination of the immunosuppressive dose of FK506, the neuroregenerative effects of different doses of FK506 were explored by assessing nerve regeneration in 80 rats after tibial nerve transection and repair. The control group received no FK506, whereas the other four groups were given daily doses of FK506 of 0.25, 0.5, 1.0, or 2.0 mg/kg. Rats were euthanized at three time points (25, 30, and 35 days), to fully investigate the effects of different FK506 dosing regimens on neuroregeneration. Histomorphometric analyses performed on postoperative days 30 and 35 demonstrated statistically significant improvements in neuroregeneration with subimmunosuppressive FK506 doses of 0.5 and 1.0 mg/kg per day. Therefore, the study demonstrated that neuroregeneration was enhanced at low doses of FK506 that were not sufficient to prevent skin allograft rejection.

Animals↗
PubMed2003

Nerve transfers to the biceps and brachialis branches to improve elbow flexion strength after brachial plexus injuries.

OBJECT: In this study the authors evaluated the outcome in patients with brachial plexus injuries who underwent nerve transfers to the biceps and the brachialis branches of the musculocutaneous nerve. METHODS: The charts of eight patients who underwent an ulnar nerve fascicle transfer to the biceps branch of the musculocutaneous nerve and a separate transfer to the brachialis branch were retrospectively reviewed. Outcome was assessed using the Medical Research Council (MRC) grade to classify elbow flexion strength in conjunction with electromyography (EMG). The mean patient age was 26.4 years (range 16-45 years) and the mean time from injury to surgery was 3.8 months (range 2.5-7.5 months). Recovery of elbow flexion was MRC Grade 4 in five patients, and Grade 4+ in three. Reinnervation of both the biceps and brachialis muscles was confirmed on EMG studies. Ulnar nerve function was not downgraded in any patient. CONCLUSIONS: The use of nerve transfers to reinnervate the biceps and brachialis muscle provides excellent elbow flexion strength in patients with brachial plexus nerve injuries.

Adolescent↗
PubMed2002

Current approach to radial nerve paralysis.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Identify all potential points of radial nerve compression and other likely causes of radial nerve injury. 2. Accurately diagnose both surgical and nonsurgical causes of radial nerve paralysis. 3. Define a safe and effective approach to the surgical release and reconstruction of the radial nerve. Radial nerve paralysis, which can result from a complex humerus fracture, direct nerve trauma, compressive neuropathies, neuritis, or (rarely) from malignant tumor formation, has been reported throughout the literature, with some controversy regarding its diagnosis and management. The appropriate management of any radial nerve palsy depends primarily on an accurate determination of its cause, severity, duration, and level of involvement. The radial nerve can be injured as proximally as the brachial plexus or as distally as the posterior interosseous or radial sensory nerve. This article reviews the etiology, prognosis, and various treatments available for radial nerve paralysis. It also provides a new classification system and treatment algorithm to assist in the management of patients with radial nerve palsies, and it offers a simple, five-step approach to radial nerve release in the forearm.

Algorithms↗
PubMed2002

Multilevel nerve compression and muscle imbalance in work-related neuromuscular disorders.

BACKGROUND: Work-related upper limb disorders have come under increasing scrutiny and become a frustrating problem. METHODS: A unifying hypothesis to explain the multiplicity of symptoms with work related neuromuscular disorders is outlined. This multifactorial problem includes physical, individual, and psychosocial factors. Abnormal postures and positions may compress nerves or may alter muscle length resulting in secondary compressive forces on nerves or in muscle imbalances. Evaluation should identify all nerve compression levels and muscle imbalance in the arm and cervicoscapular region. Management must include patient education, postural correction, and an exercise program to address the multiple nerve compression levels and muscle imbalance. RESULTS AND CONCLUSIONS: The etiology of work related neuromusculoskeletal disorders is multifactorial and successful management must address all contributing factors. Appropriate conservative management will relieve symptoms in most patients. Surgery should be reserved for those few patients with evidence of a specific diagnosis who have failed conservative management.

Arm↗
PubMed2002

Effect of nondepleting anti-CD4 monoclonal antibody (Rib 5/2) plus donor antigen pretreatment in peripheral nerve allotransplantation.

Peripheral nerve allotransplantation allows the reconstruction of injuries with long nerve gaps that are otherwise unsalvageable. In this study, the efficacy of anti-CD4 monoclonal antibody (mAb) combined with donor antigen pretreatment in prolonging the survival of short peripheral nerve allografts was investigated in a rodent model. Such an approach could potentially avoid the need for systemic immunosuppression and its concomitant morbidities. Buffalo rats received either nerve isografts or nerve allografts from Lewis rats. Untreated isograft and allograft groups were used as controls. Allograft recipients received either a single dose of RIB 5/2, a nondepleting anti-CD4 mAb, a single dose of Lewis splenocytes, or both antigen and RIB 5/2, 7 days prior to transplantation. Flow cytometric analysis verified that the T-lymphocyte population was maintained, while CD4 expression was downregulated by RIB 5/2. Histologic evaluation demonstrated better regeneration in the allograft recipients receiving both donor antigen and antibody, compared to recipients of untreated allografts or treatment with antigen or antibody alone.

Animals↗
PubMed2002

Surgical treatment of a long thoracic nerve palsy.

A 17-year-old patient presented with a long thoracic nerve palsy following an idiopathic onset of weakness to the serratus anterior muscle. With no evidence of recovery 3.5 months following onset of serratus anterior weakness, the patient underwent a thoracodorsal to long thoracic nerve transfer to reinnervate the serratus anterior muscle. Follow-up examination 6.5 years following the nerve transfer revealed no scapular winging, full range of motion of the shoulder and no reported functional shoulder restriction. We conclude that a thoracodorsal to long thoracic nerve transfer results in good functional recovery of the serratus anterior muscle.

Adolescent↗
PubMed2002

Pathophysiology of nerve compression.

Both ischemic and mechanical factors are involved in the development of compression neuropathy. Experimental studies suggest a dose response curve such that the greater the duration and amount of pressure, the more significant is neural dysfunction. With changes of axonal injury, significant neurologic dysfunction would be anticipated; however, the vast majority of patients with CTS present with symptoms in association with electrophysiologic findings of demyelination (prolonged latency). Frequently, the prolongation in latency is minimal and some patients may even present with normal electrodiagnostic studies, still complaining of significant symptomatology. This would support the concept that in the majority of patients with CTS, the symptoms relate to problems with the connective tissue "container" of the nerve rather than pathology of the nerve fiber itself. This would be in keeping with the histopathologic findings of fibrosis, with thickening of the external epineurium and perineurium. These changes would interfere with blood flow as the vessels pass through the epineurium and perineurium and produce dynamic ischemia to the nerve fibers. As well, this fibrosis would decrease the excursion of the nerve fibers, resulting in traction, and prevent the nerve fibers themselves from going through a full range of movement without traction and decreased gliding. The importance of neural gliding and movement of the nerve in the extremity has been recently emphasized in the clinical management of patients with multilevel nerve compression. Clinical maneuvers that put the nerve on stretch will provoke patients' symptoms and have been used to diagnose specific compression neuropathies (neural tension test). Similarly, physical therapy modalities to stretch the nerves and restore neural gliding are frequently successful in relieving patients' symptoms [33]. This physical therapy approach is based on the premise that the connective tissue "container" of the nerve is tight and short and needs to be mobilized. This is in keeping with the histopathologic findings of increased connective tissue at the perineurial and epineurial levels. A greater understanding of the pathophysiology of compression neuropathy will have immediate impact on our management of this problem and likely result in emphasis on conservative management and physical therapy rather than surgical intervention.

Carpal Tunnel Syndrome↗
PubMed2002

Effect of age on thrombosis and morbidity in the mouse-limb transplantation model.

Murine models of limb transplantation have been recently described. Because of the technical challenge, non-technical factors that influence the success rate and are easily controlled should be considered. This study investigated the effect of recipient animal age on anastomotic thrombosis, morbidity, and mortality. Twelve allogeneic heterotopic hindlimb transplants were performed using the femoral vessels with end-to-end arterial and end-to-side venous anastomoses. Group 1 (n=8) consisted of 2 to 3-month-old mice weighing 17 to 20 g, and Group 2 (n=7) included 7 to 8-month-old mice weighing 24 to 27 g. In Group 1, 6/8 (75 percent) transplants were successful, while in Group 2, only 1/7 (14 percent) allografts survived (p<0.05). A statistically significant difference in the incidence of vascular compromise of the ipsilateral recipient hindlimb was also noted (p<0.01). The authors conclude that although smaller, juvenile, inbred mice have a higher anastomotic patency rate, with greater collateral vasculature in the hindlimbs, and are therefore more suitable for limb transplantation research.

Age Factors↗
PubMed2002

Peripheral nerve regeneration in the apolipoprotein-E-deficient mouse.

Apolipoprotein E (apo E) is thought to mediate the reutilization of myelin cholesterol for nerve regeneration. Prior research suggests that apo E is not essential for nerve regeneration following a nerve crush injury. This study was conducted to determine if apo E is essential for nerve regeneration after nerve transection and interposition nerve autograft. Nerve regeneration of transgenic apo E-deficient mice was compared with control mice after a sciatic nerve neurolysis and repair and interposition autograft. Histomorphometric assessment and histology were performed on distal nerve segments to evaluate nerve regeneration. Apo E-deficient mice demonstrated no difference in total fiber number or nerve fiber width when compared with controls; however, the nerve fiber density and percent neural tissue of apo E-deficient mice were significantly less than controls following nerve repair. Apo E deficiency does not affect nerve regeneration. It is likely that the low nerve fiber density and the low percent neural tissue associated with apo E-deficiency result from impairment in the disposal of myelin debris.

Animals↗
PubMed2002

Distal anterior interosseous nerve transfer to the deep motor branch of the ulnar nerve for reconstruction of high ulnar nerve injuries.

Proximal ulnar nerve injuries can result in loss of intrinsic muscle function of the hand, and distal nerve transfers provide nerve coaptation close to the target muscle. This retrospective chart review evaluated patient outcome following a distal nerve transfer of the anterior interosseous nerve (AIN) to the deep motor branch of the ulnar nerve. There were eight patient charts reviewed, three women, and five men. The mean patient age was 38 years (standard deviation: 22 years). The mean time from injury to surgery was 3 months (standard deviation: 3 months), and mean postoperative follow-up time was 18 months (standard deviation: 11 months). All patients had reinnervation of the ulnar nerve intrinsic hand muscles with improved postoperative lateral pinch and grip strength. One patient had a secondary tendon transfer. No functional deficit in performing tasks in pronation was reported. The distal nerve transfer of the AIN to the deep motor branch of the ulnar nerve provides good reinnervation of the ulnar-nerve-innervated intrinsic muscles of the hand.

Adult↗
PubMed2002

Patient outcome after surgical management of an accessory nerve injury.

OBJECTIVE: This study assessed patient outcome following surgical reconstruction of the accessory nerve after an iatrogenic injury. STUDY DESIGN: A retrospective chart review of 8 patients was performed. RESULTS: There were 3 men and 5 women in the study, and the mean time between injury and nerve graft/repair surgery was 5 months. Four injuries were sustained during a lymph node biopsy. Electromyography revealed a complete accessory nerve injury in all cases. In 6 cases, a nerve graft was required (mean length, 3.6 cm), and in 2 cases, a direct nerve repair was possible. The trapezius muscle was successfully reinnervated in all cases. In total, full shoulder abduction was achieved in 6 cases; in the remaining 2 cases, the patients achieved shoulder abduction to 90 degrees. CONCLUSION: Functional deficit after accessory nerve injury is significant. Nerve graft/repair reconstruction reliably yields a satisfactory result, providing good scapular rotation and thus good shoulder function.

Accessory Nerve↗
PubMed2002

Prevalence of smoking, obesity, diabetes mellitus, and thyroid disease in patients with carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) has been associated frequently with physical factors and personal factors including smoking, obesity, diabetes mellitus, and hypothyroidism. The purpose of this retrospective case-control study was to evaluate the prevalence of personal factors in patients with CTS compared with a normal control group. The charts of 514 patients who underwent a carpal tunnel release procedure and 100 control subjects were examined for history of smoking, obesity, diabetes, and hypothyroidism. Compared with the control subjects, there were significantly less CTS patients who smoked (p < 0.001; odds ratio, 0.17). However, there were more CTS patients than control subjects who were obese (p = 0.02; odds ratio, 1.77), had diabetes (p = 0.03; odds ratio, 3.02), and had hypothyroidism (p = 0.02; odds ratio, 3.70). These results support previous reports that CTS is multifactorial, with such factors as obesity, hypothyroidism, and diabetes but not smoking to be more prevalent in this group of CTS patients.

Body Mass Index↗
PubMed2002

Patient self-reported outcome after ulnar nerve transposition.

Subjective outcome was assessed in 100 patients with cubital tunnel syndrome at least 2 years after anterior transmuscular transposition of the ulnar nerve. The mean time from surgery was 37 months (standard deviation, 10 months). The patient sample of 119 operated cases included 81 unilateral procedures and 19 patients had bilateral procedures. The mean time between surgeries was 7 months. Sixty-one patients who underwent unilateral procedures reported improvement, and there was no difference in 13 unilateral cases. Thirteen patients who underwent bilateral procedures reported improvement in both arms. Postoperatively symptoms were significantly less than those preoperatively: pain, p = 0.001; cold sensitivity, p = 0.001; tingling, p = 0.05; and numbness p = 0.08. In 51 cases, patients reported normal sensation and in 45 cases patients reported normal strength. Reported outcome was significantly better in nonsmokers than in smokers (p = 0.02) but was not significantly different in patients with workers' compensation/litigation (p = 0.51), obesity (p = 0.16), abnormal preoperative nerve conduction studies (p = 0.21), concomitant carpal tunnel syndrome (p = 0.95), or brachial plexus nerve compression (p = 0.35).

Adult↗
PubMed2002

Effects of tobacco smoke on recovery after nerve crush injury in rats.

The effects of tobacco smoke on nerve healing after crush injury was studied in a rat model. Thirty-six animals were randomized equally into smoke-exposed or nonsmoke-exposed groups. Two nerve crush injuries were performed on the right posterior tibial nerve of each animal at 4-week intervals to mimic a sustained or chronic nerve injury. Recovery of the two groups was assessed with walking track analysis and nerve histomorphometry. There was no difference in the rate of nerve recovery based on walking track analysis in the smoke-exposed animals compared with nonexposed animals. The study also failed to demonstrate any significant difference between the two groups as assessed by histomorphometric criteria.

Analysis of Variance↗
PubMed2002

Failure of cyclosporin a to rescue peripheral nerve allografts in acute rejection.

Prevention and control of graft rejection remain essential in the investigation of peripheral nerve allotransplantation. Although use of cyclosporin A (CsA) has been shown to suppress successfully the rejection of nerve allografts, limited information exists concerning use of this drug to arrest rejection in progress, and thereby effect salvage of these grafts. The aim of this study was to determine the efficacy of CsA in the treatment of ongoing acute rejection of peripheral nerve allografts. Buffalo rats received posterior tibial nerve grafts from either Lewis or Buffalo donor animals and were divided into five groups: group 1 received isografts and no CsA treatment (n = 8), group 2 received allografts with continuous CsA therapy (n = 10), group 3 received allografts with no treatment (n = 7), group 4 received allografts with initiation of CsA therapy delayed until 3 weeks after the procedure (n = 11), and group 5 received allografts with an interrupted course of CsA (n = 15). All grafts were harvested at 10 weeks. Histomorphometric analysis demonstrated comparable nerve regeneration in groups 1 and 2 and good regeneration in group 3 animals, despite cellular infiltrate suggestive of rejection. At 3 weeks after surgery, group 4 animals showed early rejection and significantly less neuroregeneration than positive controls at 10 weeks after delayed initiation of CsA therapy. Finally, group 5 animals showed early regeneration at 3 weeks but significantly lesser regeneration by 10 weeks after interruption of therapy. In this experimental protocol, CsA was ineffective in rescuing histologically proven rejection in progress.

Analysis of Variance↗
PubMed2002

The effects of rapamycin in murine peripheral nerve isografts and allografts.

The FKBP-12-binding ligand FK506 has been successfully used to stimulate nerve regeneration and prevent the rejection of peripheral nerve allografts. The immunosuppressant rapamycin, another FKBP-12-binding ligand, stimulates axonal regeneration in vitro, but its influence on nerve regeneration in peripheral nerve isografts or allografts has not been studied. Sixty female inbred BALB/cJ mice were randomized into six tibial nerve transplant groups, including three isograft and three allograft (C57BL/6J) groups. Grafts were left untreated (groups I and II), treated with FK506 (groups III and IV), or treated with rapamycin (groups V and VI). Nerve regeneration was quantified in terms of histomorphometry and functional recovery, and immunosuppression was confirmed with mixed lymphocyte reactivity assays. Animals treated with FK506 and rapamycin were immunosuppressed and demonstrated significantly less immune cell proliferation relative to untreated recipient animals. Although every animal demonstrated some functional recovery during the study, animals receiving an untreated peripheral nerve allograft were slowest to recover. Isografts treated with FK506 but not rapamycin demonstrated significantly increased nerve regeneration. Nerve allografts in animals treated with FK506, and to a lesser extent rapamycin, however, both demonstrated significantly more nerve regeneration and increased nerve fiber widths relative to untreated controls. The authors suggest that rapamycin can facilitate regeneration through peripheral nerve allografts, but it is not a neuroregenerative agent in this in vivo model. Nerve regeneration in FK506-treated peripheral nerve isografts and allografts was superior to that found in rapamycin-treated animals. Rapamycin may have a role in the treatment of peripheral nerve allografts when used in combination with other medications, or in the setting of renal failure that often precludes the use of calcineurin inhibitors such as FK506.

Animals↗