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Biomedical subjects

J C Firrell

Publications and source records attributed to J C Firrell.

At least 19 recordsLinked to original sources

Blood flow in a chronic entrapment neuropathy model in the rabbit sciatic nerve.

A model of chronic entrapment neuropathy in the rabbit sciatic nerve was developed to try to elucidate the pathogenesis of chronic nerve entrapment. A non-compressive Silastic cuff was wrapped around the nerve at the mid-thigh level in eight rabbits. A sham operation that only elevated the sciatic nerve was performed in seven control rabbits. Six months later, the blood flow in the cuffed and the control sciatic nerves was determined with intra-arterially injected microspheres. Blood flow was significantly reduced in the entrapped nerve, compared to control nerves, but only in the segment proximal to the cuff. After surgical release of the cuff, the blood flow significantly increased in the proximal segment. This suggested that decreased blood flow may occur, but not necessarily at the site of nerve entrapment. Nerve conduction velocity changes were also consistent with an entrapment neuropathy. However, there were no significant quantitative morphometric changes at the nerve entrapment site, that is, in myelin thickness/nerve diameter ratio, distribution of axon sizes, and mean nerve fiber diameter. This indicates that only a mild entrapment was created.

Animals↗

An inexpensive new device to provide random rewards for behavioral studies.

Behavior modification in rats often involves controlling the frequency of providing food rewards. This is accomplished with computer-controlled devices or equipment purchased specifically for this purpose. Investigators currently choose from a few commercially available models, but each has its disadvantages or limitations, including a high cost (about US$1000). Computer-controlled devices can also be expensive and need a dedicated machine and software packages to perform the tasks. We designed a custom-built device to reward an action randomly from 1 out of 10 times to 10 out of 10 times. The device can be manufactured easily and inexpensively (about US$150). It has been in use for several months in our laboratories with no malfunctions.

Animals↗

Single pedicle vascularized double joint transfer: anatomic study of two models.

This study examined the anatomic structures that communicate between the tibial and fibular digital arteries of the second toe at the distal phalanx to identify a channel for retrograde blood flow from the dominant pedicle to the distal joint flap. We also assessed the feasibility of two models designed to mobilize toe joints to perform single pedicle vascularized double-joint transfer. The continuity of the vascular pathway in both models was demonstrated by microfil injection and angiographic study. The average mobile distance between the PIP joint and the MTP joint was 5.6 +/- 0.6 cm in model I and 5.1 +/- 0.4 cm in model II. The dissection and mobilizing procedures of the neurovascular pedicle are more complicated and extensive in model II than in model I, and the risk of jeopardizing vascularity of the distal joint flap is higher. Both models may be suitable to replace two adjacent metacarpophalangeal (MCP) joints in the hand or two nonadjacent MCP joints (excluding the thumb) separated by no more than one normal metacarpal.

Arteries↗

Ischemic preconditioning versus intermittent reperfusion to improve blood flow to a vascular isolated skeletal muscle flap of rats.

OBJECTIVES: We investigated whether intermittent restoration of blood flow just before reperfusion after ischemia could create beneficial effects similar to ischemic preconditioning, which involves intermittent stoppage of blood flow just before ischemia. METHODS: Male Sprague-Dawley rats were prepared with vascular isolated cremaster muscles, then subjected to 4 hours of ischemia and 60 minutes of reperfusion. Arteriole diameters and capillary perfusion were measured by using intravital microscopy. Four groups were used: (1) untreated, (2) ischemic preconditioning (IP), (3) intermittent reperfusion (IR), and (4) ischemic preconditioning plus intermittent reperfusion (IP+IR). RESULTS: Our results showed that IP significantly attenuated both ischemia/reperfusion-induced vasospasm and capillary noreflow. IR was effective in attenuating vasospasm in terminal arterioles. However, IR alone was unable to significantly attenuate capillary no-reflow. Combining both IP and IR achieved the best results. CONCLUSION: Our results suggest both ischemic preconditioning and intermittent reperfusion are useful techniques for attenuating ischemia/reperfusion injury.

Animals↗

Kienböck disease and negative ulnar variance.

We compared the degree of ulnar variance, measured on standardized radiographs of the wrist, in forty-four patients who had Kienböck disease with that in ninety-nine control subjects who had been selected from a general clinic population and had radiographs of the wrist. The purpose of our study was to determine if there is a true relationship between negative ulnar variance and the development of Kienböck disease. Gender was not found to influence the degree of ulnar variance, but an association was found between age and negative ulnar variance in both the control subjects and the patients who had Kienböck disease. The findings of the present study confirmed an association between negative ulnar variance and the development of Kienböck disease even after correction for the influence of age on the measurement of ulnar variance.

Adolescent↗

Blood flow in mobilized nerves: results in a rabbit sciatic nerve model.

The purpose of this study was to evaluate the immediate effect on capillary blood flow of surgical mobilization of 15 cm of the rabbit sciatic and tibial nerve. Capillary nerve blood flow was determined with 16-micron radioactive microspheres. Thirty-seven rabbits were divided into six groups. In the control group A (n = 7), the in situ nerve blood flow was determined. In group B (n = 7), the nerve was mobilized, leaving only the proximal and distal endoneurial vascular supplies; blood flow increased compared with in situ values in most segments. In group C (n = 5), the nerve was mobilized as in group B, but also transected distally; blood flow was markedly decreased in the distal segments but was maintained up to a diameter-to-length ratio of 1:63. In group D (n = 6), the nerve was not mobilized, but was transected proximally and distally; blood flow increased in all segments. In group E (n = 5), the nerve was mobilized and transected proximally and distally, leaving only nerve branches intact; blood flow was significantly higher in segments of the nerve from which nerve branches originated with the nerve receiving blood flow through its branches. In group F (n = 6), the nerve was mobilized, all extrinsic vessels except one were transected, and the proximal and distal nerve was transected; flow was maintained to a diameter:length ratio of 1:41 from the source of blood flow. Therefore, it does appear that long lengths of nerve may be mobilized and transposed while maintaining sufficient blood flow.

Animals↗

Postoperative infection in a double-occupancy operating room. A prospective study of two thousand four hundred and fifty-eight procedures on the extremities.

The purposes of this study were to determine the rate of infection associated with elective outpatient operations on an extremity, performed in a double-occupancy operating room (one operating room designed to accommodate two separate operating teams), and to determine which factors influenced this rate. We evaluated the records of 2458 consecutive patients who had had such a procedure, performed by one of nine surgeons during a two and one-half-year period, and in whom the operative wound had been classified as clean (without a drain) or clean-contaminated (with a drain). The information regarding the factors associated with the operation and the operating-room environment was recorded for each patient at the time of the operation. Each wound was inspected periodically in the attending surgeon's office for at least thirty days postoperatively. Using definitions established by the Centers for Disease Control, the attending surgeon determined the presence of infection primarily by judging whether there was purulent drainage or whether erythema or swelling at the operative site was beyond that expected from the procedure. Of the 2458 patients, thirty-seven (1.5 per cent; 95 per cent confidence interval, 1.1 to 2.1 per cent) had infection of the operative wound. Only eight patients (0.3 per cent) had deep infection, with seven of the infections necessitating a reoperation. Infection developed in thirty of the 2311 clean wounds, a rate of 1.3 per cent (95 per cent confidence interval, 0.9 to 1.8 per cent), and in seven of the 147 clean-contaminated wounds, a rate of 4.8 per cent (95 per cent confidence interval, 2.3 to 9.5 per cent) (p = 0.001). No cross-contamination occurred between patients who had infection. The rate of infection was not related to the number of patients who were operated on in the same room at the same time. Logistic regression analysis, used to account for confounding factors, demonstrated a significant association between the classification of the wound (use of a drain) and a higher rate of infection (p = 0.006) as well as between the instillation of a topical steroid solution and a lower rate of infection (p = 0.04). It also demonstrated a significant difference, with respect to the rate of infection, among individual surgeons (p = 0.02).

Adolescent↗

Functional degradation of the rabbit sciatic nerve during noncompressive segmental ischemia.

The purpose of this study was to evaluate functional degradation in a nerve with a local ischemic segment created without a direct compression effect. Ischemia of one segment of a rabbit sciatic nerve was induced by stripping the nerve's extrinsic blood supply along 15 cm. Blood flow of both in situ and ischemic nerves was quantitatively measured with radioactive microspheres in six serial segments in seven animals. The flow in one middle segment of the stripped nerve was significantly reduced to 0.1 ml/min per 100 g (p = 0.006). In another eight animals, both in situ and stripped nerves were metabolically challenged with repetitive stimuli (200 Hz). Conduction velocity and peak amplitude were measured before stimuli, after 30 and 60 minutes of stimuli, and after a 30-minute recovery period. Conduction velocity was reduced in both nonischemic and stripped nerves during prolonged repetitive stimulation. Peak amplitude was reduced slightly in the nonischemic group and markedly in the stripped group. Normal or higher values were seen again in both groups during the recovery period. It was demonstrated, therefore, that conduction properties of the nerve, especially amplitude, can be affected by localized ischemia in one segment.

Action Potentials↗

Which setting of the dynamometer provides maximal grip strength?

The purpose of this study was to determine which setting of the clinical dynamometer produced maximal grip strength and to correlate that setting with characteristics of the individual. Using a computerized isometric dynamometer, the maximal grip strength was determined in 288 normal asymptomatic hands in 4- to 78-year-old individuals at five dynamometer size settings. The majority of hands (256, or 89%) had a maximal grip strength at setting II. Mean body weight and mean height were lower in the group that had a maximal strength at or equal to setting I than in those individuals with maximal setting II and above. However, no clear significant correlation between body mass or hand size and maximal setting was evident. Those with a maximal grip at setting III or IV did not have larger hands or other features that differed from those with maximal settings at II. If measured at setting II only, maximal grip strength would have been underestimated in about 10% of individuals, but the error was small, ranging from 2% to 24%. Since no feature was identified that predicted maximal grip strength setting, it is recommended that grip strength of all patients should be routinely measured at setting II, irrespective of age, weight, or hand dimensions.

Adolescent↗

Sciatic function index, nerve conduction tests, muscle contraction, and axon morphometry as indicators of regeneration.

The purpose of this study was to determine which parameters were the best measure of nerve regeneration, assuming that the sciatic functional index (SFI) represented the "gold standard." Three different sciatic functional indexes and 11 commonly used electrophysiologic and morphologic indicators of regeneration were all determined in 24 rats 12 weeks after one of three lesions was created in the sciatic nerve. With linear regression analysis, only fiber/axon diameter ratio (D/d) and myelin thickness/axon diameter ratio showed statistically significant correlations with sciatic functional index (r = 0.55 and 0.53, respectively). The other 11 parameters had poorer correlation. Therefore, if sciatic functional index is the best measure of comprehensive nerve function, then other parameters are not. It is probable that each parameter measures some different component of the regeneration process. A stepwise multiple linear regression analysis produced a model that included D/d, nerve conduction velocity, and nerve action potential amplitude that gave a slightly better correlation (r = 0.67). The relatively poor correlation between sciatic functional index and the other parameters of nerve function indicates that all nerve regeneration studies must be interpreted carefully before comparisons are made. Furthermore, the best measure of nerve function remains unproved or undiscovered in the experimental animal.

Animals↗

Effect of ischemia and three different perfusion solutions on the rabbit epiphyseal growth plate.

An isolated vascularized knee joint model was used (1) to determine the minimum ischemia time that produced growth retarding damage to the epiphyseal plate and (2) to evaluate whether intra-arterial perfusion could reduce the ischemia damage. Experiment 1 consisted of 31 rabbits in 5 groups: 0, 2,4,6, and 8 hr of warm ischemia produced by clamping the pedicle. Experiment 2 consisted of 18 rabbits in which 10 ml of one of (1) Euro-Collins, (2) University of Wisconsin solution, or (3) heparinized blood were perfused through the joint without ischemia. Experiment 3 consisted of 21 rabbits in which one of the three solutions was perfused for a short period during 6 hr of ischemia. Growth of the tibia was followed radiographically every month over 3 months, and the growth plates were evaluated histologically after sacrifice. Results showed that at least 6 hr of ischemia was needed before longitudinal growth was reduced; less ischemia time caused overgrowth. Histologic damage was found in all animals to some degree. Perfusion alone without ischemia had no detrimental effect on growth or histology. The growth reduction at 6 hr of ischemia was minimized by perfusion with every solution. Heparinized blood was the most effective and Euro-collins was the least effective.

Adenosine↗

Arteriole constriction following ischemia in denervated skeletal muscle.

Arteriolar diameters and flow patterns were determined in the isolated rat cremaster muscle following 4 hr of total ischemia. Two groups of six rats each were studied--an innervated group and a denervated group. The microcirculation was observed using intravital microscopy, and the images were recorded on videotape. The whole arterial tree was scanned, and the smallest vessel diameter for each arterial segment was measured. Preischemic mean arteriole diameters were significantly larger in the denervated group, compared to the innervated group. Following ischemia, during the 3 hr of reperfusion, the main (AI) cremaster arteriole from both the innervated and denervated groups constricted to 50 to 70 percent of pre-ischemic diameters. However, the actual diameters (as distinct from percentage change) were not significantly different between the innervated and denervated groups. There were significant differences in flow patterns. Some A2 and A3 vessels became temporarily nonflowing vessels (either open but without low, or closed by severe spasm). These poorly-functioning vessels were significantly more common in the denervated group. Furthermore, this phenomenon of temporary no-flow persisted longer in the denervated group over the 3-hr reperfusion period. These observations suggest that the ability to recover quickly from an ischemic insult is less in tissues that have been denervated.

Animals↗

Vascular filling and protein extravasation in three varieties of vascularized venous nerve grafts.

The purpose of this study was to compare the microcirculation perfusion and plasma-protein extravasation in varieties of venous nerve grafts. Venous nerve grafts were created from the left median nerve and brachial vein of the rabbit. The vein was interposed between (a) brachial artery to brachial artery (AVA); or (b) brachial artery to proximal cephalic vein (AVV); or (c) brachial vein to brachial vein (VVV). A standard, vascularized, nerve graft was created in the opposite limb, to serve as a control, and the untouched sciatic nerve served as a second control. Microcirculation perfusion and permeability of endoneurial vessels were evaluated using intravenously-injected albumin labelled with Evans blue dye (EBA) as a fluorescent tracer within 1 hr after surgery. Six hours after surgery, the nerves were removed and evaluated for tracer content and distribution. Extravasation of EBA was extensive in both AVA and AVV forms of the venous nerve graft, suggesting good perfusion but showing significant protein leakage and edema. VVV, on the other hand, had only slight extravasation, comparable to untouched sciatic nerves. Although the number of vessels filled with blood in the VVV was 69 percent of the vascularized nerve graft, the lack of marked extravasation may make it the venous nerve graft of choice.

Anastomosis, Surgical↗

Evaluation of a local microsphere injection method for measurement of blood flow in the rabbit lower extremity.

The precision of a modified microsphere technique to measure blood flow in the hind limb of the rabbit was determined. Regional (local) injections made via a catheter in the aorta and blood withdrawn through a catheter in the hind limb enabled deposition of a high concentration of microspheres in the tissues while minimizing the number of microspheres needed for accurate measurement. 95Niobium and 141cerium-labeled 16 microns diameter microspheres were used. Blood flow was measured in 15 locations of muscle and skin for simultaneous injections into the aorta and left ventricle (group A), simultaneous injections of a mixture into the left ventricle (group B), and ventricular injections given 1 h apart (group C). No significant differences in mean blood flow measurements were found. Correlation coefficients between local and ventricular injections ranged from 0.89-0.99 and between 0.994 and 0.999 for two simultaneous ventricular injections. The variability over time was greater, with correlations between the first and second injections ranging from 0.13-0.939. Precision of the local technique compared with the ventricular technique can be kept within 30% with five or six animals. The advantage of this technique over ventricular injections is in the measurement of blood flow in small tissue samples when the number of microspheres deposited from ventricular injections is insufficient.

Animals↗

Evaluation of sympathetic control of digital blood flow.

A noninvasive strain-gauge method of measuring blood flow in the digit was used to assess the influence of the sympathetic system in the digit. The sympathetic system was stimulated by the sudden application of ice to the neck, thus avoiding in the hand local reflexes and responses to cold. Seventeen normal subjects responded in similar fashion. Maximum flow reduction ranged from 26% to 92%, with a mean of 61%. This method should be useful diagnostically and for research when sympathetic reactivity, in contrast to basal sympathetic tone, needs to be determined.

Adult↗

Origin of Schwann cells in peripheral nerve allografts in the rat after withdrawal of cyclosporine.

The origin of Schwann cells in peripheral nerve allografts following rejection was determined by immunohistochemistry. Sciatic nerve allografts from ACI-RT1a rats were transplanted into Lewis-RT1l sciatic nerves using epineurial sutures. Isografts were taken from Lewis-RT1l rats. Cyclosporine (CsA) was administered subcutaneously daily, 5 mg/kg for 12 weeks, to the rats in each group. Allografts with CsA were sacrificed in groups at 12, 14, 16, 20, 24, and 36 weeks postoperatively during the rejection and recovery phase. Allografts and isografts without CsA were evaluated at 3, 6, 12, and 24 weeks. Nerves were frozen and cross sections immunohistochemically stained against Lewis rat HLA (RT1) and against Schwann cells (S-100 antigen). Allografts without CsA demonstrated minimal reaction to anti-Lewis compared to control isografts, which stained positively at all times. Schwann cells were not as well-stained in the allografts. Allografts with CsA showed reactivity to S-100 at 12 weeks, but minimal activity to Lewis antibody. Minimal reactivity to both S-100 and Lewis existed at 16 weeks, but increased gradually by 24 and 36 weeks. Therefore, Schwann cells from the recipient migrate into the graft and replace the Schwann cells from the donor following rejection.

Animals↗

Blood flow and tissue survival in the rabbit venous flap.

The extent of venous flow, revascularization, local fluid imbibition, and metabolic status was evaluated in an experimental venous flap model. Thirty-six rabbits divided into six groups of six rabbits each had a 3.5 x 2.5 cm venous flap elevated along the thoracoepigastric vein, connected only by its proximal and distal vein, and sutured back. A composite graft of the same size was created on the contralateral side. Venous flaps survived 14 days, while composite grafts consistently did not. The vascular network was partially filled with fluorescein tracer within an hour after flap creation, even with an underlying Silastic sheet. Filling improved over several days, consistent with rapid revascularization. Composite grafts showed no immediate filling and delayed revascularization. Venous flow was apparently insufficient to enhance metabolism, since both glucose and lactate levels were equivalent between venous flaps and composite grafts. This supports the concept that an enhanced revascularization may be the primary mechanism of survival for venous flaps.

Animals↗

Pre-operative factors and treatment outcome following carpal tunnel release.

The outcome of carpal tunnel release was evaluated retrospectively in 60 hands of 53 patients followed for six to 33 months (median ten months). Outcome was considered good in 27% (pain, weakness, and numbness were essentially resolved); fair in 42% (most of the symptoms improved); and poor in 32% (symptoms persisted or worsened). Patients whose pre-operative work activity was considered physically strenuous were associated with a slightly but significantly poorer outcome (60% good or fair) compared to those in light work or with no employment (89% good or fair). Proportionately fewer patients returned to their original work when they previously engaged in strenuous activity, ranging from 27% for those using air guns to 80% in light work. It appears that the highest chance of a poor outcome from carpal tunnel release occurs in patients who have either associated symptoms of thoracic outlet syndrome or physically strenuous work activities.

Adult↗