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Biomedical subjects

S E Mackinnon

Publications and source records attributed to S E Mackinnon.

At least 55 records · Page 3Linked to original sources

Nerve transfers. New options for reconstruction following nerve injury.

Surgical reconstruction of proximal level nerve repair or long nerve grafts have provided less than optimal results, presenting the opportunity for investigation of alternate reconstructive techniques. Good motor function following an injury to a motor nerve requires a maximal number of motor axons reaching the motor end plate within a critical time period. Nerve transfers eliminate the need for a nerve graft by allowing a direct end to end nerve repair without tension. This article reviews surgical options using nerve transfers for patients with upper and lower extremity nerve injuries.

Humans↗

Revascularization of peripheral nerve autografts and allografts.

The timing and mechanisms of peripheral nerve revascularization were investigated using a 2-cm sciatic nerve graft model in 58 rats. Epineurial perfusion was consistently established by 48 hours and endoneurial perfusion by 72 hours. The pattern of endoneurial perfusion was "all-or-none"--either all or none of the vessels in a fascicle exhibited blood flow. Conventional allografts exhibited similar revascularization dynamics and patterns. Capping the ends of the autograft with Silastic significantly delayed revascularization; no flow was observed at 4 days, and only a peripheral rim of perfused fascicular vessels was observed at 7 days. These patterns suggested that the primary method of revascularization in the conventional graft was longitudinal inosculation; no evidence of peripheral neovascularization or dependence on the graft bed as a source of revascularization was observed. The introduction of a major histocompatibility complex barrier between the grafted tissue and the recipient animal did not alter the timing or the mechanics of blood flow reestablishment.

Animals↗

Lack of association between outcome measures of nerve regeneration.

Studies of nerve regeneration in rodents utilize at least one of three classes of outcome measures: electrophysiology, morphometry, and functional tests. The assumption that these measures are correlated was tested utilizing a data set of 16 variables. Significant correlations (Spearman's rho, P < or = 0.05) were found within variable classes; however, none were found between classes. The three commonly utilized outcome measures do not measure the same phenomenon but rather discrete aspects of nerve regeneration.

Animals↗

Cold preserved nerve allografts: changes in basement membrane, viability, immunogenicity, and regeneration.

Rat sciatic nerve graft segments were harvested and pretreated by either placement in the University of Wisconsin Cold Storage Solution at 5 degrees C and storage from 1 to 26 weeks, or repeatedly freezing (-40 degrees C) and thawing (20 degrees C). Following pretreatment, grafts were transplanted as either syngeneic or allogeneic nerve grafts. Storage and freeze-thawing did not affect the Schwann cell basal lamina or laminin distribution of the peripheral nerve. Graft cell viability decreased with increasing time of storage, with some viable cells detectable even after 3 weeks of storage. Freeze-thawed grafts were not viable. Increasing time of storage led to decreasing immune response and graft rejection, but improved regeneration. Freeze-thawed and 26-week stored allografts were nonimmunogenic and rejection was not seen, but regeneration was delayed compared to autografts. Graft storage may become a useful adjunct to clinical nerve allografting to permit elective scheduling of surgery, provide greater time for preoperative tissue testing, and possibly blunt the immune response.

Animals↗

The value of an operating microscope in peripheral nerve repair. An experimental study using a rat model of tibial nerve grafting.

The aim of this study was to test the hypothesis that the use of an operating microscope improves the results of peripheral nerve repair. Tibial nerve grafting was carried out on 48 Fischer rats divided into 2 groups: in one, a loupe was used, and in the other a surgical microscope. At 5 months after grafting, recovery was evaluated by functional, electromyographic, and morphometric tests. The mean motor nerve conduction velocity was 26.77 +/- 9.37 m/sec in the group where the loupe was used compared with 44.19 +/- 11.36 m/s when the microscope group was used. The soleus muscle weight and the diameter of myelinated fibres also confirmed better regeneration in the microscope group. These results clearly indicate that it is essential to use the microscope for peripheral nerve repair.

Analysis of Variance↗

End-to-side neurorraphy: a long-term study of neural regeneration in a rat model.

This study evaluated long-term reinnervation of an end-to-side neurorraphy and the resultant functional recovery in a rat model. The divided distal posterior tibial nerve was repaired to the side of an intact peroneal nerve. Control groups included a cut-and-repair of the posterior tibial nerve and an end-to-end repair of the peroneal nerve to the posterior tibial nerve. Evaluations included walking-track analysis, nerve conduction studies, muscle mass measurements, retrograde nerve tracing, and histologic evaluation. Walking tracks indicated poor recovery of posterior tibial nerve function in the experimental group. No significant difference in nerve conduction velocities was seen between the experimental and control groups. Gastrocnemius muscle mass measurements revealed no functional recovery in the experimental group. Similarly, retrograde nerve tracing revealed minimal motor neuron staining in the experimental group. However, some sensory staining was seen within the dorsal root ganglia of the end-to-side group. Histologic study revealed minimal myelinated axonal regeneration in the experimental group as compared with findings in the other groups. These results suggest that predominantly sensory regeneration occurs in an end-to-side neurorraphy at an end point of 6 months.

Action Potentials↗

Pain responses in patients with upper-extremity disorders.

The purpose of this study was to evaluate the relationship between pain response factors and upper-extremity disorders associated with work-related compensable disorders. In this retrospective study, the charts of 113 patients were examined. Compensation was not found to have any statistically significant association with pain levels. The degree of functional overlay in these patients, indicated by pain questionnaire scores, differed only slightly between compensated and noncompensated patients and indicated no significant difference between the 2 groups, except that the compensated group used a higher number of descriptors to describe their pain (p = .0143). These results indicate that compensation affects the verbalization of pain but does not affect the degree of pain experienced. Working status was found to be significantly correlated with a better ability to cope with stress at home, suggesting that employment status may be a more important factor than compensation status in the presentation of these patients.

Adaptation, Psychological↗

Surgeons' concern and practices of protection against bloodborne pathogens.

OBJECTIVE: To evaluate surgeons' concern regarding risk awareness and behavioral methods of protection against bloodborne pathogen transmission during surgery. METHODS: A 29-item questionnaire was sent to 914 surgeons from two universities and two surgical societies. RESULTS: The questionnaire was returned by 768 active surgeons. Slight or moderate concern about contracting human immunodeficiency virus (HIV) was reported by most surgeons; 8% reported extreme concern and 4% reported no concern. In total, 605 surgeons reported having been vaccinated against hepatitis B; surgeons in practice <7 years were most likely to be vaccinated. Most surgeons did not routinely use double gloves: 92 of 768 surgeons reported that they always use double gloves when performing surgery, and 83 reported that they usually use double gloves. There was a statistically significantly higher proportion of surgeons who always or usually use double gloves who also had hepatitis B vaccinations. Most surgeons incorrectly estimated the seroconversion rates with exposure to a patient with HIV (66% incorrect), hepatitis B (88% incorrect), or hepatitis C (84% incorrect). Most surgeons never or rarely report needle-stick injuries, and only 17% always report needle-stick injuries. CONCLUSIONS: Most surgeons underestimate the risk of bloodborne pathogens and do not routinely use double gloves.

Attitude of Health Personnel↗

Nerve injection injury with botulinum toxin.

The therapeutic use of botulinum toxin (Botox) is increasing in popularity. Previous studies have shown that various drugs, especially when injected intrafascicularly, can cause major nerve damage. This study evaluates the potential for neurotoxicity of botulinum toxin in a rat sciatic nerve model. Lewis rats were randomly assigned to one of six groups (n = 10/group). Group 1, 2, and 3 rats received, respectively, an intrafascicular, extrafascicular, and extraneural injection of 50 microl of botulinum toxin (50 UI/ml). Group 4, 5, and 6 rats received 50 microl of 10% phenol as a positive control. Five animals received saline as a negative control. Animals were sacrificed at 2 and 7 weeks. Nerves were harvested and processed for histology and morphometry. Nerves in all botulinum toxin groups retained a normal architecture without cellular infiltration or demyelination. The number and diameter of fibers, the thickness of myelin, and the percentage of neural tissue were comparable with normal controls. Nerves injected intraneurally with phenol presented with severe damage, demyelination, and inflammation at 2 weeks and showed signs of early regeneration at 7 weeks. This study demonstrates that in a rat model, even direct intraneural injection of botulinum toxin caused no damage. This information should encourage the reconstructive surgeon to consider broader applications of this drug.

Animals↗

Long-term observation of the effect of peripheral nerve injury in neonatal and young rats.

The purpose of this study was to observe functional recovery and motoneuron death after nerve transection-and-repair in neonatal versus young animals. One hundred nine Lewis rats underwent posterior tibial nerve transection-and-repair at 6 or 22 days of age. Fifty-two and fifty-seven nerves at the 6- and 22-day times were used for endpoint analysis at 1, 3, 10, and 14 months. These assessments included serial functional walking track analysis, electrophysiologic studies, muscle mass evaluation, motoneuron counts with retrograde horseradish peroxidase tracing, and histologic and morphometric nerve analysis. Walking track analysis and nerve conduction velocity indicated significantly poorer functional regeneration in the 6-day-old group than in the 22-day-old group. Muscle mass in the 6-day-old group did not recover as well as in the 22-day-old group. Motoneuron numbers stained with horseradish peroxidase were less in the 6-day-old group than in the 22-day-old group. In contrast, morphometric analysis did not reach significance. This study suggests that the same nerve injury sustained in a neonatal rat is less likely to demonstrate functional recovery than one sustained in a young rat.

Animals↗

Indefinite survival of peripheral nerve allografts after temporary Cyclosporine A immunosuppression.

It is hypothesized that unlike solid organ transplants immunosuppression of peripheral nerve allografts is needed only for the finite time period required for regeneration of proximal host nerve axons through the allograft and subsequent re-establishment of host end-organ connections. The aim of this study was to explore the consequences of temporary and continuous systemic Cyclosporine A (CsA) immunosuppression upon peripheral nerve allograft survival. Buffalo rats received Lewis nerve allografts under CsA immunosuppression (5 mg/kg/day) either continuously for 20 weeks, or for only 10 weeks followed by abrupt withdrawal. At 20 weeks, the nerve segments from both groups were regrafted into naïve Buffalo or Lewis recipients without further immunosuppression. These grafts were compared with isografts, unimmunosuppressed allografts and allografts immunosuppressed for 10 weeks in situ. By eight weeks following regrafting, the secondary Lewis recipients had rejected the temporarily immunosuppressed allografts and accepted the continuously immunosuppressed allograft, while the secondary Buffalo recipients accepted both the temporarily and continuously immunosuppressed allografts as assessed by histology and morphometry. Functional recovery was earlier in secondary recipient strain animals that received temporarily immunosuppressed allografts in comparison to those that received continuously immunosuppressed allografts. Analysis of secondary recipients of temporarily immunosuppressed allografts demonstrated greater in vitro MLR and LDA reactivity than did those receiving continuously immunosuppressed allografts. These findings support the hypothesis that donor alloantigens are lost or replaced by the recipient after immunosuppression withdrawal. Moreover, the change to recipient antigenicity in the nerve allograft is retarded and incomplete under continuous CsA immunosuppression, resulting in acceptance by both secondary donor and recipient strains upon regraftment.

Journal Article↗

Nerve injury in repetitive motion disorders.

Nerve compression in repetitive motion disorders is being recognized with increasing frequency. The pathophysiology of chronic nerve compression spans a broad spectrum beginning with subperineurial edema and progressing to axonal degeneration. These changes depend on the amount and duration of the compressive forces. Certain postures or positions in the upper extremity will increase pressures around certain nerves increasing pressure exposure. Evaluation of these patients with chronic nerve compression should include examination at all levels of potential entrapment in the upper extremity to identify all sites of compression.

Chronic Disease↗

Induction of donor-specific tolerance to rat nerve allografts with portal venous donor alloantigen and anti-ICAM-1/LFA-1 monoclonal antibodies.

BACKGROUND: Expendable autologous nerve available for repair of nerve injuries is limited. Cadaveric allografts could provide adequate nerve for grafting but are susceptible to rejection and currently require chronic systemic immunosuppression. METHODS: Age-matched Buffalo (RT1B) rats randomly assigned to 7 experimental groups received either a Lewis (RT1L) rat posterior tibial-sciatic nerve allograft or a Buffalo (RT1B) syngeneic isograft. Recipients were treated with anti-intercellular adhesion molecule-1 (anti-ICAM-1) and anti-leukocyte function-associated antigen-1 (anti-LFA-1) monoclonal antibodies (mAbs), intraportally administered ultraviolet B (UVB)-irradiated donor splenocytes, a combination of mAbs and UVB-irradiated donor splenocytes, or no immunosuppression. RESULTS: Histologic, electrophysiologic, and functional evaluation of nerve allografts 8 weeks after transplantation revealed a synergistic improvement in nerve allograft regeneration when monoclonal antibodies were combined with UVB-irradiated donor splenocytes. In vitro immunologic assessment correlated with the in vivo allograft function by demonstrating a donor-specific suppression of the recipient's response in mixed lymphocyte culture (MLC), cytotoxic T lymphocyte assay (CTL), and reduced T cell interleukin-2 production in both the group receiving UVB-irradiated alloantigen alone and the group receiving a combination of UVB antigen and mAbs. CONCLUSIONS: The combined use of mAbs directed against ICAM-1 and LFA-1 adhesion molecules with intraportally administered UVB modified donor antigen prevents nerve allograft rejection and synergistically improves nerve regeneration.

Animals↗

Antibody to transforming growth factor beta reduces collagen production in injured peripheral nerve.

Epineurial scarring in peripheral nerve after injury inhibits normal axonal regeneration primarily due to fibroblast deposition of type I collagen. The transforming growth factor beta (TGF-beta) family is an important class of signaling molecules that has been shown to stimulate fibroblasts to produce collagen. The aim of this study was to design a prototypic therapeutic system in which the neutralization of TGF-beta in crushed rat sciatic nerve would decrease collagen formation. A total of 45 experimental Lewis rats were used. Group 1 animals (20 rats) sustained a unilateral crush injury to the sciatic nerve with injection of phosphate buffer solution. Group 2 animals (20 rats) sustained a unilateral crush injury to the sciatic nerve with injection of phosphate-buffered saline and goat, anti-rat, panspecific TGF-beta antibody. Group 3 control animals (five rats) underwent only exposure of sciatic nerve with injection of antibody. All animals were killed at 14 days and sciatic nerve specimens were harvested at that time. Slides of experimental tissue were processed using a 35S-labeled oligomer for procollagen alpha-1 mRNA, then dipped in photographic emulsion and examined by darkfield autoradiography. Morphometric analysis of pixel counts was then performed. A significant reduction in total pixel count per high-power field and in total number of fibroblasts per high-power field was found in crushed rat sciatic nerve treated with anti-TGF-beta antibody when compared with those treated only with phosphate-buffered saline. These findings are consistent with successful reduction in procollagen induction after a crush injury by topical administration of blocking antibody against transforming growth factor beta. The concept of growth factor blockade for therapeutic collagen reduction is attractive in the context of nerve injury, and the current article provides a model for future clinical application.

Animals↗

The effect of duration of muscle denervation on functional recovery in the rat model.

The effect of long-term denervation on neuromuscular recovery was studied in a rat hind limb model. The posterior tibial nerve was transected and repaired immediately or after denervation periods of 2 weeks, or 1, 3, 6, 9, or 12 months. Six months following reconstruction excellent axonal regeneration was seen across all nerve repairs irrespective of periods of denervation. However, there was a precipitous and profound decrease in the recovery of both muscle mass and integrated motor function if the reconstruction was delayed for longer than 1 month. Rather than a progressive change proportional to the length of the denervation period, significant, more discrete changes occurred sometime after 1 month of denervation that precluded a full recovery of muscle mass. Integrated motor function quantified using walking track analysis was impaired even after immediate nerve repair.

Animals↗

Evaluation of cutaneous vibration thresholds in medical transcriptionists.

This study was designed to determine whether vibration thresholds of transcriptionists varied significantly from the thresholds of individuals not exposed to keyboard activities. Using a multifrequency vibrometer, we obtained vibration threshold values from 31 medical transcriptionists who perform work on computer keyboards and compared them to values obtained from 40 control subjects. Thresholds tended to become more abnormal at higher frequencies, although this difference was statistically significant only at frequencies of 125 Hz, 250 Hz, and 500 Hz in the index and small fingers. Vibration thresholds were not found to increase significantly with age or years of occupation. Vibration thresholds were significantly increased in medical transcriptionists at the higher frequencies, suggesting subtle neural dysfunction.

Adult↗