Biomedical subjects

D A Hunter

Publications and source records attributed to D A Hunter.

At least 37 records · Page 2Linked to original sources

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

Nicotine replacement therapy.

OBJECTIVE: To review the literature on nicotine dependence, nicotine pharmacology, health consequences associated with the use of nicotine, and nicotine replacement therapies used to aid smokers who are nicotine dependent. DATA SOURCES: A review of articles, book bibliographies, and published studies identified by a search of the MEDLINE database from 1982 to 1996 on nicotine dependence, nicotine addiction, nicotine withdrawal, smoking, smoking cessation, smoking intervention, nicotine pharmacology, nicotine pharmacokinetics, nicotine pharmacodynamics, and nicotine replacement therapies. STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria were published randomized, double-blind trials of at least 12 weeks' duration, meta-analyses, and panel consensus guidelines. DATA SYNTHESIS: Cigarette smoking and tobacco use have met the surgeon general's primary criteria as well as additional criteria for drug dependence. Drug dependence requires that the drug produce psychoactive effects. Nicotine has been identified as the cause of tobacco dependence. First, nicotine provides positive reinforcement by stimulating nicotinic receptors to promote high self-administration rates. Second, nicotine causes a negative reinforcement in the form of withdrawal symptoms when nicotine is withheld after chronic use. Nicotine replacement therapy reduces the severity of withdrawal symptoms in smokers abstaining from tobacco. Nicotine replacement therapy allows the smoker to focus on psychosocial aspects of tobacco abstinence while receiving relief from withdrawal symptoms. The long-term effectiveness and health benefits of nicotine replacement therapy coupled with nonpharmacologic approaches have been clearly established. Smoking cessation has received wide attention from the public and medical communities; it is complex and has several interwoven factors to be considered. The psychological, behavioral, and physical components have to be understood before designing a treatment plan. The most successful approaches to smoking cessation involve multicomponent, multisession behavioral treatment programs as a foundation coupled with pharmacologic intervention. Pharmacists can play a key role in initiating behavior change and ensuring the safe and proper use of nicotine replacement in order to produce the desired outcome. CONCLUSIONS: The optimum choice in nicotine replacement depends on the individual's needs and coping abilities. Individualized nicotine replacement coupled with nonpharmacologic interventions produces the highest rate of success for abstinence from nicotine.

Administration, Cutaneous↗

PubMed1998

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↗

PubMed1997

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↗

PubMed1997

The effect of ammonium sulfate injection on peripheral nerve.

Local anesthetic drugs with prolonged nerve-block effect would have clinical application for postoperative or neuromatous pain relief. This study evaluated the possibility of peripheral nerve neurotoxicity by injection of 10 percent ammonium sulfate. Both intrafascicular and extrafascicular injection of 10 percent ammonium sulfate were tested in the rat sciatic nerve model. One percent lidocaine HCl, 5 percent phenol, and normal saline were similarly injected for comparison. Using histologic studies and motor function evaluation with walking-track analysis, 10 percent ammonium sulfate was found to be neurotoxic when it is injected intrafascicularly; however, extrafascicular injection of this drug did not cause significant nerve injury. The neurotoxicity of the 10 percent ammonium sulfate solution was intermediate between the neurotoxicity of 0.1 percent lidocaine hydrochloride and the marked neurotoxicity of 5 percent phenol solution.

Ammonium Sulfate↗

PubMed1997

End-to-side neurorrhaphy resulting in limited sensory axonal regeneration in a rat model.

This study evaluated reinnervation of an end-to-side neurorrhaphy and the resultant functional recovery in a rat model. The cut distal posterior tibial nerve was repaired to the side of an intact peroneal nerve. In one group, the epineurium of the peroneal nerve was left intact; in another group, the epineurium was stripped; in the third experimental group, a perineurial slit was created. Evaluations included walking track analysis, nerve conduction studies, muscle mass measurements, retrograde nerve tracing, and histologic evaluation. Walking tracks indicated poor functional recovery. No significant difference in nerve conduction between the experimental and control groups was seen. Gastrocnemius muscle mass measurements revealed no functional recovery in the end-to-side groups. Retrograde nerve tracing revealed minimal staining of motor neurons. However, sensory neuronal staining of the dorsal root ganglia occurred in all groups. Histology revealed minimal myelinated axonal regeneration. These results suggest that predominantly sensory neural regeneration occurs in an end-to-side neurorrhaphy at an end point of 16 weeks.

Anastomosis, Surgical↗

PubMed1996

Cyclosporine A inhibits lymphocyte migration into ovine peripheral nerve allografts.

Lymphocyte migration into nerve allografts was measured to estimate the cyclosporine A (CsA) dose required to suppress rejection. Twelve outbred sheep received daily subcutaneous CsA at 0, 5, 10, or 15 mg/kg/day for 2 weeks prior to implantation of multiple heterotopic subcutaneous nerve grafts. Lymphocyte migration was determined after 7 days by an intravenous pulse of autologous 111indium-labeled lymphocytes and subsequent quantitation of gamma radioactivity in nerve tissue (CPM/g, mean +/- SEM). Measurement by radioimmunoassay revealed a dose-dependent increase in blood cyclosporine levels. Lymphocyte migration into autografts (404+/-44) was significantly less than migration into allografts (16,554+/-2,049), in control animals (P < 0.01). A dose-dependent inhibition of lymphocyte migration into nerve allografts was observed with counts of 7,662+/-1,692, 4,083+/-1,112, and 1,561+/-232 in sheep receiving 5, 10, or 15 mg/kg/day of CsA, respectively. Daily CsA administration produced effective blood levels and immunosuppression sufficient to inhibit lymphocyte migration into nerve allografts.

Animals↗

PubMed1996

Peripheral nerve allograft preservation improves regeneration and decreases systemic cyclosporin A requirements.

Peripheral nerve allografting is limited by the need for long-term systemic immunosuppression. The purpose of this study was to determine if nerve allograft preservation reduced the requirements for systemic Cyclosporin A (CsA) immunosuppression. One hundred twenty Lewis rats were randomized to one of seven experimental groups. Group 1 received a 2-cm Lewis posterior tibial nerve autograft. Groups 2-7 received 2-cm ACI posterior tibial nerve allografts. The allograft group was then further subdivided into three groups of two receiving daily subcutaneous injections of 0, 2.5, or 5.0 mg/kg of CsA for 12 weeks. Within each CsA dose, one group received a fresh while the other received a preserved allograft. Preserved grafts were stored in University of Wisconsin solution for 7 days at 5 degrees C prior to implantation. Animals from each group were sacrificed at 6, 12, and 20 weeks postoperatively. Evaluations included histomorphometry, electrophysiology, and serial walking track analysis. Histology revealed varying degrees of nerve regeneration in all groups at 6, 12, and 20 weeks. For a given CsA dose, the group receiving the preserved graft revealed evidence of better nerve regeneration by all histomorphometric parameters including fiber width and density, percentage neural tissue, and total fiber number. There was no statistical difference in walking track analysis between groups at 4 weeks. By 20 weeks, functional recovery statistically poorer than autograft was seen only in the fresh allograft groups receiving 0 or 2.5 mg/kg of CsA. Identical electrophysiologic findings were seen at 20 weeks. These results suggest that nerve graft preservation may decrease systemic immunosuppression requirements while improving functional recovery. As well, storage of nerve grafts is feasible and would facilitate elective surgery and less costly reconstructive repair.

Analysis of Variance↗

PubMed1996

Long-segment nerve allograft regeneration in the sheep model: experimental study and review of the literature.

Experimental work in the field of nerve allotransplantation has dealt with the feasibility of nerve allografts reconstructing nerve gaps. In the majority of studies, the nerve gap studied has been short, and some degree of regeneration has been achieved, even in the untreated allograft. To better approximate clinical nerve-allograft reconstruction, a series of long-segment (8-cm) nerve allografts were performed in the ovine model. Twenty outbred ewes were randomized into two experimental groups with four experimental conditions. Animals received nerve allografts treated under one of the following conditions: fresh nerve autograft, fresh nerve allograft, cold-preserved nerve autograft, or cold-preserved nerve allograft. The nerve grafts were examined and compared at 6 and 10 months, using histological, morphometric, and electro-physiologic analyses. The results of the study demonstrated that, while excellent regeneration occurred across the nerve autograft, the long nerve allograft could not support axonal elongation. Similarly, cold nerve preservation did not enhance regeneration. The sheep animal model allows for investigation of the long nerve gap and may be beneficial in a better correlation of experimental nerve transplantation with clinical conditions.

Animals↗

PubMed1995

Immunosuppressive effect of monoclonal antibodies to ICAM-1 and LFA-1 on peripheral nerve allograft in mice.

This study evaluated the immunosuppressive effect of monoclonal antibodies against cell surface molecules in a murine peripheral nerve allograft model. After nerve allografting, 18 recipients were treated with both anti-intercellular adhesion molecule-1 (ICAM-1) and anti-lymphocyte function-associated molecule-1 (LFA-1) monoclonal antibodies in low or high dose. Nerve allografts were harvested at 8 weeks for histologic and morphometric evaluation. Recipients were subsequently challenged with skin grafts at 9 weeks and a cytotoxic assay at 12 weeks. The majority of the antibody-treated allografts (13 of 18) showed excellent regeneration comparable to the autografts with preservation of the normal nerve architecture and scant cellular infiltrate. All untreated allografts demonstrated severe structural disorganization with cellular infiltrate consistent with acute rejection. In the high dose group, the mean skin graft survival time from nerve donor mice, but not third-party mice, was significantly prolonged. (17.5 vs. 11.3 days). Similarly, the cytotoxic activity against nerve donor alloantigen was significantly suppressed. These preliminary findings suggest that antibody therapy alone can facilitate nerve regeneration in a murine nerve allograft model.

Animals↗

PubMed1995

Monoclonal antibodies against ICAM-1 and LFA-1 prolong nerve allograft survival.

In a rat nerve allograft model, specific immunosuppression was approached with monoclonal antibodies (MAbs) against cell-surface molecules. After engraftment, recipients were treated with antiintercellular adhesion molecule-1 (ICAM-1) and antilymphocyte function-associated antigen-1 (LFA-1) MAbs for 14 days. Functional recovery was evaluated biweekly. Electrophysiological and histological assessments were performed at 6 and 16 weeks. Immunologic responsiveness in the recipients was assessed with a cytotoxic T lymphocyte (CTL) assay at 16 weeks and skin grafts at 18 weeks. The untreated allograft group demonstrated complete disruption of fascicular architecture with poor nerve regeneration. The MAb-treated allografts maintained well-organized nerve architecture with a dense population of well-myelinated fibers. These animals showed functional and electrophysiological recovery. Suppression of CTL activity was nerve donor specific and the survival time of nerve donor skin grafts was prolonged, suggesting induction of alloantigen-specific tolerance. MAbs therapy directed against ICAM-1/LFA-1 presents a new approach for the management of the peripheral nerve allograft response.

Animals↗

PubMed1995

Regeneration across preserved peripheral nerve grafts.

The potential to store nerve grafts for a prolonged period of time was assessed in a rat sciatic nerve model. Three-centimeter syngeneic nerve grafts were stored in Belzer/University of Wisconsin cold storage solution at different temperatures (5 degrees C, 22 degrees C, or 37 degrees C) for varying time periods (6 h, 24 h, or 3 weeks) prior to transplantation. Functional assessment using serial walking track analyses revealed no difference between storage times and temperatures. At 14 months postengraftment, the conduction velocities and the number of myelinated fibers that had regenerated across all grafts stored at 5 degrees C for all time periods tested were superior to grafts stored at either 22 degrees C or 37 degrees C. Nerve grafts stored for up to 3 weeks at 5 degrees C acted as effective conduits for proximal regenerating fibers and resulted in histologic, electrophysiologic, and functional results equivalent to fresh nerve grafts. Nerve graft storage may be applicable to nerve allografts and potentially provide allograft material that requires reduced or no associated host immunosuppression.

Action Potentials↗

PubMed1994

Penicillin allergies.

Explore the source record for details and available documents.

Adverse Drug Reaction Reporting Systems↗

PubMed1994

Nerve crush injuries--a model for axonotmesis.

Nerve crush is a commonly used experimental model in the rat; however, a standard method of inducing this injury has not been defined. This study examined six crush techniques that are frequently used and characterized the subsequent nerve injury. Five types of nerve crush using a No. 5 jeweler's forceps and a sixth using a 30-s single crush with a serrated hemostat were studied in the posterior tibial nerve of the Lewis rat. Regeneration was evaluated using serial walking track assessments at 1, 2, 4, 6, and 8 weeks postoperatively. Nerve conduction studies and histological examination were performed at 2 days, 2 weeks, and 8 weeks. Blood-nerve barrier breakdown was observed at 2 days and recovered by 2 weeks. By 4 weeks normal walking track patterns were obtained in all groups. A pattern of Wallerian degeneration and axonal regeneration was noted at 2 weeks, with histological recovery in all groups by 8 weeks. Nerve crush, induced by any of the six methods tested, was similar and provides a reliable model of axonotmesis.

Animals↗

PubMed1994

The regulation of collagen in fetal skin wounds: mRNA localization and analysis.

The deposition of collagen in fetal skin wounds has been shown in several animal models. The authors used a radiolabeled RNA antisense probe, complementary to the mRNA for the alpha-1 chain of human procollagen type I, to assess regulation of this collagen species in fetal and adult rabbit wounds. Dorsal skin wounds were placed on fetal and maternal animals at the beginning of the third trimester, and were harvested 3, 5, and 7 days later. In situ RNA/RNA hybridization was performed on suitable specimens, and morphometric analysis was carried out with a computerized LECO image analyzer. Fetal wounds exhibited an inflow of mesenchymal cells that produced collagen type I at levels higher than the surrounding tissue; this activity was highest on days 3 and 5 after wounding. Adult wounds had increased fibroblast presence by day 7, producing collagen type I at levels higher than those of adjacent unwounded tissue. Morphometric analysis of the signal produced by in situ hybridization and of the number of cells producing the signal in a given field showed that fetal wounds appear to produce collagen type I by an increase in the number of cells in the area of the wound--not by induction of the gene for procollagen type I. In contrast, adult wounds had both fibroblast migration and induction of procollagen type I mRNA synthesis. These findings imply multilevel regulation of collagen production in the adult and posttranslational regulation in the fetus.

Animals↗

PubMed1993

Regeneration across 'stepping-stone' nerve grafts.

The ability of small nerve segments interposed between synthetic conduits to increase the total nerve gap distance across which successful nerve regeneration would occur was studied. Fifty adult male Lewis rats were randomized into five groups. In Group I a segment of resected sciatic nerve was repaired by a nerve graft. Group II had alternating silicone tubing/nerve graft/silicone tubing replacement of the resected nerve segment (single stepping stone group). Group III had silicone tubing/nerve graft/silicone tubing/nerve graft/silicone tubing repair of the nerve deficit (double stepping stone). Group IV had a single long silicone conduit repair. Group V control underwent a sham operation. Nerve regeneration was evaluated using walking track pattern analysis, electrophysiologic assessment and histomorphological evaluation. 'Stepping stone nerve grafts' enhanced regeneration across nerve gaps in comparison to a single long conduit, but were inferior to a single long nerve graft. In the repair of long nerve gaps, the use of multiple short conduits with interposed short nerve segments could provide a source of trophic factors to enhance regeneration.

Animals↗

PubMed1993

Walking track analysis: utilization of individual footprint parameters.

Functional assessment of rat sciatic, tibial, and peroneal nerve injuries was performed using walking track analysis. Individual walking print length (PL), toe spread (TS), and intermediate toe spread (ITS) values were measured up to 24 weeks after specific nerve transection, with or without repair. Sciatic and tibial nerve manipulation initially affected all footprint measurements, consistent with loss of intrinsic and extrinsic motor function. After sciatic repair, TS demonstrated partial recovery without any substantial recovery in PL or ITS, compared with sciatic transection values. By contrast, after tibial repair, PL values recovered dramatically, between 16 and 24 weeks, to levels not significantly different from control subjects. This was not observed after tibial transection without repair. TS recovered partially, whereas ITS recovered to control levels by 20 weeks after tibial repair. Peroneal transection resulted in multiple contractures, rendering this group unmeasurable at 4 weeks. After peroneal repair, only the PL reflected significant loss of function at 2 weeks, recovering to control values by 8 weeks. Manual TS measurements in nonwalking rats did not reflect functional nerve regeneration. Thus, individual PL measurements alone can be used to characterize functional recovery after tibial and peroneal nerve injury, whereas TS reflected recovery after sciatic nerve injury.

Animals↗