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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
PubMed1992

Subcutaneous injection of oral cyclosporin A solution.

Cyclosporin A (CyA) is the agent of choice for immunosuppression in the majority of rodent organ and tissue allotransplantation experiments. Subcutaneous injection of suitably dissolved pure CyA powder preparation is the acceptable standard of drug administration. We investigated the possibility of using oral CyA solution in an injectable form and compared its availability with that of the standard solution in a rat model. Oral CyA solution diluted in placebo (olive oil) and standard solution prepared from pure compound were injected subcutaneously at a dose of 5 mg/kg/day to two groups of rats. Trough whole blood CyA concentrations were measured on day 10 following initiation of treatment. Blood CyA levels of the standard solution group (1,167 +/- 246 micrograms/liter, mean +/- SD) were virtually identical to those of the oral solution group (1,105 +/- 179 micrograms/liter; P greater than 0.05). In addition, the oral solution was easier to prepare and caused less injection site morbidity than the standard solution. We conclude that placebo-diluted oral CyA solution may be safely injected subcutaneously to rats and results in consistent blood levels, comparable to those achieved with standard solution prepared from pure compound.

Administration, Oral↗
PubMed1992

Chronic cyclosporin A therapy in rats.

We investigated the pharmacokinetics of cyclosporin A (CsA) blood levels and drug toxicity in a chronic rat study in which long-term (30 weeks) CsA was administered. Ninety Lewis rats received subcutaneous CsA at 5 mg/kg/day for 12 weeks, at which time CsA injections were stopped in 50 animals. The remaining 40 rats were maintained on 5 mg/kg CsA daily until week 18 and then switched to an alternate day dosing until week 30. All rats were observed daily and weighed weekly. Whole blood CsA levels were determined by a commercially available radioimmunoassay kit. The daily dosing regimen resulted in greatly elevated trough CsA levels (greater than 1,600 micrograms/liter) and substantial chronic systemic toxicity, with weight loss and death in eight animals. Alternate day dosing reduced trough levels (mean 1,311 micrograms/liter) and decreased toxicity. Chronic administration by the subcutaneous route resulted in a considerable depot effect, with constancy of drug levels over a 48 hr dosing interval and a slow decline of drug levels (15 days) upon cessation of treatment. These results underscore the importance of monitoring both body weight and blood CsA levels in rodent studies when CsA is employed. Investigators should be aware of drug accumulation with chronic therapy and the consequent need to modify dosing to prevent toxicity.

Animals↗
PubMed1992

Provocative sensory testing in carpal tunnel syndrome.

This study reports the relationship between three clinical tests in the diagnosis of carpal tunnel syndrome and the stages of nerve compression. Assessments of 158 patients with carpal tunnel syndrome were reviewed retrospectively. 77% of patients had at least one of the clinical signs present. The incidence of positive pressure-provocative and Phalen's tests were similar and more likely to occur in combination than separately. Tinel's sign was more likely to be positive in the later stages of nerve compression. Our results suggest that the presence or absence of a provocative test is dependent upon the severity of the nerve compression.

Adult↗
PubMed1992

An assessment of regeneration across peripheral nerve allografts in rats receiving short courses of cyclosporin A immunosuppression.

While peripheral nerve reconstruction could benefit from the use of nerve allografts, long term immunosuppression for non-vital organ transplantation is controversial. This study investigated the effectiveness of short course Cyclosporin A immunosuppression. Fourteen Lewis (RT1l) rats were the recipients of 3 cm sciatic nerve grafts from ACI (RT1a) donors, repaired to the transected sciatic nerve of the recipient animal. Animals were treated with Cyclosporin A (5 mg/kg/day) for eight weeks. Neuromuscular function was assessed every two weeks by sciatic function index determinations until 20 weeks. Electrophysiological, histological and morphological evaluations were performed at 14 (n = 6) and 20 weeks (n = 8) postengraftment. Rats had significantly improving functional studies from four to eight weeks (P = 0.01). Function decreased following cessation of Cyclosporin A treatment. Rats evaluated at 14 weeks had histological evidence of graft rejection with inflammatory cell infiltration, extensive demyelination and remyelination, and some Wallerian degeneration. Rats demonstrated improvement in morphological parameters and motor function from 14 to 20 weeks after engraftment. In this sciatic nerve allograft model, short course Cyclosporin A immunosuppression, although resulting in an initial episode of graft rejection, was successful in permitting good long term functional regeneration of neuromuscular function.

Animals↗
PubMed1992

Reinnervation of distal sensory nerve environments by regenerating sensory axons.

This study investigated the specificity of sensory nerve regeneration in a primate model. In adult cynomolgus monkeys, the femoral nerve was explored in the groin and two sensory branches identified. A sensory branch was sectioned and introduced into the proximal channel of a Y-shaped silicone chamber. This proximal sensory nerve stump was given distal choices of distal sensory nerve graft or distal sensory nerve which was intact to the distal sensory cutaneous receptors. After eight months, histological analysis confirmed axonal growth directed towards both the distal nerve graft and the distal nerve intact to the distal cutaneous receptors. However, the number of nerve fibres directed towards the distal nerve was significantly greater than the number of nerve fibres directed towards the nerve graft (P less than 0.004). These results suggest that while both distal nerve graft and distal intact nerve act as specific targets to regenerating proximal primate nerve, the presence of an intact distal end-organ positively enhances sensory regeneration.

Animals↗
PubMed1992

Sensory recovery after median nerve grafting.

Fourteen patients were evaluated prospectively after median nerve grafts. Twelve male and two female patients with a mean age of 41 years were included. Mean time since surgery was 4 years. Detailed sensory evaluations were completed. Statistical evaluation analyzed relationships between object identification, sensory tests, and graft length. According to the S-0 to S-4 grading system, 11 patients were considered to be S-3+ or greater. Recovery of moving two-point discrimination of 2 to 3 mm. was achieved by 50% of the patients. Strong correlations were found between object identification and static two-point discrimination, moving two-point discrimination, and graft length. Cutaneous pressure threshold and vibration threshold correlated weakly with object identification.

Adult↗
PubMed1992

Continuous intravenous regional anesthesia.

This study evaluates the effectiveness of continuous intravenous regional anesthesia for prolonged operations on the upper extremity. The factors evaluated include patient's sex and age, number of procedures performed, tourniquet on and off times, anesthetic doses, adjunctive drugs used, technical complications, and side effects. Seventy-two procedures were done on 34 patients. The first tourniquet time averaged 58 minutes. Off time averaged 10 minutes. Second tourniquet time averaged 33 minutes, and the mean total tourniquet time was 91 minutes. The mean first anesthetic dose was 275 mg. Mean second anesthetic dose was 128 mg. Mean total anesthetic dose was 402 mg. There were two (6%) technical complications and two (6%) patients had side effects. Continuous intravenous regional anesthesia offers the prolonged anesthesia of brachial plexus block or general anesthesia and the safety, reliability, and ease of intravenous regional anesthesia. Continuous intravenous regional anesthesia should be considered an alternative choice of anesthetic method in upper extremity surgery.

Adult↗
PubMed1992

Evaluation of digital prostheses.

Fifty-one digital prostheses were made for 33 patients between 1986 and 1988. A questionnaire was developed to assess the patients' satisfaction with these prostheses and was administered 6 months and 3 years after the prostheses were made. The majority of patients requested prostheses for esthetic reasons. While they reported satisfaction with the appearance of the prostheses, at 3 years 36% of the patients no longer continue to use the prostheses.

Adult↗
PubMed1992

Intraneural anatomy of the median nerve provides "third web space" donor nerve graft.

To determine the feasibility of using the fascicular group to the third web space as a source of nerve graft material for bridging of median nerve gaps, a study of the intraneural anatomy of the median nerve was carried out in 23 fresh cadaver specimens. The pattern of plexus formation between the third web-space group and the remainder of the median nerve was determined. The average length of the third web-space fascicular group that could be separated from the median nerve proper prior to plexus intermingling was 24.5 cm. Cross-sectional areas of the graft and the remaining nerve were 4.43 mm2 and 13.76 mm2, respectively. The number of nerve fibers in the third web-space group was 4,847 and in the remaining median nerve, 13,486. Between February, 1989 and October, 1991, this technique has been used on 11 patients to provide donor nerve material for nerve gaps of 3 to 6 cm in the median nerve.

Adolescent↗
PubMed1992

A technique for the treatment of neuroma in-continuity.

A surgical technique for the management of a neuroma in-continuity, in which motor function is preserved and sensory function is reconstructed with nerve grafting, is presented. Tedious and potentially damaging dissection within the neuroma in-continuity is avoided. The functioning motor fascicles are identified proximal and distal to the injury site with electrical nerve stimulation eliciting muscle contraction. These motor fascicles are preserved. The electrically silent and nonfunctioning sensory fascicles are divided proximal and distal to the neuroma and reconstructed with autogenous nerve grafts. These nerve grafts bypass the functioning motor portion of the neuroma in-continuity.

Adult↗
PubMed1992

Verification of the pressure provocative test in carpal tunnel syndrome.

Three provocative tests (pressure, Phalen's test, and Tinel's sign) were studied in 30 patients with carpal tunnel syndrome and 30 control subjects. The pressure provocative test had a sensitivity of 100%. In contrast, Phalen's test was 88% sensitive and Tinel's sign only 67% sensitive. The pressure provocative test is a sensitive indicator of median nerve compression at the wrist with a faster reaction time than Phalen's test (mean time of 9 seconds vs 30 seconds). It is an appropriate provocative test in patients with stiff or painful wrists when wrist flexion is restricted.

Adult↗
PubMed1992

Clinical application of peripheral nerve transplantation.

Surgical reconstruction of extensive peripheral nerve injuries frequently exhausts the patient's own source of expendable autogenous nerve grafts. Nerve allografts would offer a limitless supply of graft material. A 23-cm, 10-cable sciatic nerve allograft was performed in an 8-year-old boy in September of 1988. The patient was managed with Cyclosporin A for 2 years. Forty-four months after the transplant surgery and 19 months after the cessation of Cyclosporin A therapy, the patient has evidence of nerve regeneration across the allograft with recovery of functional sensibility in his foot. In the selected patient with an otherwise irreparable nerve injury, consideration can be given to the use of a nerve allograft.

Child↗
PubMed1992

The peripheral nerve allograft in the primate immunosuppressed with Cyclosporin A: I. Histologic and electrophysiologic assessment.

Nerve regeneration across peripheral nerve allografts and control autografts in primates immunosuppressed with Cyclosporin A was quantitatively evaluated by electrophysiologic and histologic methods. Twelve cynomolgus monkeys received 3-cm autografts and allografts in contralateral ulnar nerves. They were immunosuppressed with Cyclosporin A at 25 mg/kg per day or placebo vehicle. Morphometric analysis of nerve graft and distal nerve segments was assessed at 1 year after engraftment. Quantitative electrophysiologic studies were performed percutaneously at 6 and 12 months, and compound action potentials were measured directly across the nerve grafts at 1 year. Excellent regeneration was seen across autografts and allografts in Cyclosporin A-treated and placebo-treated recipients.

Action Potentials↗
PubMed1992

The peripheral nerve allograft in the primate immunosuppressed with Cyclosporin A: II. Functional evaluation of reinnervated muscle.

Isometric contractile function was evaluated in primates receiving peripheral nerve allografts and autografts. Twelve adult male cynomolgus monkeys received both sural nerve allografts and autografts to the ulnar nerve in opposite forearms. Half the animals received Cyclosporin A (CsA) immunosuppression (25 mg/kg per day); the remaining animals received placebo. One year following nerve engraftment, isometric contractile muscle function was evaluated in reinnervated abductor digiti quinti and intact abductor pollicis brevis muscles. Maximal twitch tension (Pt), tetanic tension (P(o)), time to peak tension (tpt), rate of rise of twitch tension (DP/dt), and muscle fatigue were evaluated at optimal muscle length (L(o)). All reinnervated muscles distal to nerve autografts and allografts in both Cyclosporin A-immunosuppressed and placebo-treated animals generated equivalent maximal twitch tension, tetanic tension, and time to peak tension, with no significant difference between groups (p > 0.05 by ANOVA). There was a tendency toward increased muscle fatiguability in Cyclosporin A-treated animals (p > 0.05). However, the rate of rise of twitch tension was significantly faster in the reinnervated and intact muscles of Cyclosporin A-treated primates (p < 0.05). Evidence of excellent functional reinnervation across nerve allografts and autografts similar to that seen in histologic and electrophysiologic studies was noted. Cyclosporin A immunosuppression did not significantly enhance recovery of muscle function distal to nerve allografts in this model.

Animals↗
PubMed1992

Double and multiple "crush" syndromes. Double and multiple entrapment neuropathies.

The double crush hypothesis suggests that serial constraints to axoplasmic flow, each of which is insufficient to cause changes in function by itself, can be additive in causing ultimate dysfunction of the nerve. Careful clinical examination will be required to localize the significant levels of nerve compression. Frequently, patients will be asymptomatic in the nonprovoked position. A comparison of neurological testing "at rest" and then subsequent to provocation of the patient's symptoms may be the only mechanism by which the surgeon will be able to quantity an abnormality that corresponds to the patient's symptoms. Surgical intervention, especially when the etiologic factor is work-related, is always postponed until maximum job modification has been carried out. Surgical management of these patients without a significant change in the patient's work habits that provoked the compression neuropathies in the first instance will frequently be associated with a recurrence of symptoms when the work is resumed.

Chronic Disease↗