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Biomedical subjects

Konstantinos C Papakonstantinou

Publications and source records attributed to Konstantinos C Papakonstantinou.

4 recordsLinked to original sources

Early effect of gene therapy on a direct muscle neurotization model.

Direct nerve-to-muscle neurotization has been the subject of both clinical and experimental studies. In this study, the authors report a new animal model to test the regenerative properties of a nerve (musculocutaneous) implanted in a muscle (biceps). They also report the early effects of the application at the implantation site of exogenously administered Brain Derived Nerve Factor (BDNF) and of endogenously produced BDNF, via the administration of an adenoviral construct with a tissue-specific promotor for muscle cells (AdRSV), and containing the BDNF gene. Evaluation included behavioral testing (grooming test), electrical stimulation, Western blot analysis of the distal implanted nerve to determine the presence of locally produced BDNF, and motor end-plate staining of the biceps muscle. At the early time point of 1 week following the musculocutaneous nerve to biceps muscle implantation, there was no increased production of recombinant BDNF at the distal implanted musculocutaneous nerve, as assessed by Western blot analysis. Therefore, there was no significant difference in the behavioral evaluation of the animals at 1 week; the Terzis grooming test showed no statistical difference among groups, but a trend toward better function for the BDNF and the high-dose AdRSV-BDNF groups, compared to the control groups. There was also no difference in the histologic appearance and number of the motor end-plates at the implantation site, compared to the controls. The electrical stimulation of the MC nerve did not produce statistically significant results among the experimental groups. In this direct nerve to muscle neurotization model, the application of AdRSV-BDNF at 3 x 10 (9) pfu/ul did not show enhanced production of BDNF at 1 week.

Adenoviridae↗

Muscle preservation by prolonged sensory protection.

The functional recovery of a muscle target following nerve repair is inversely related to the denervation time: i.e., the longer the muscle denervation, the poorer the functional outcome following nerve reconstruction. The trophic and protective effects of sensory innervation to a motor nerve, following prolonged denervation (greater than 6 months), have been studied. Following proximal transection of the musculocutaneous nerve (MC) close to its C6 origin in 10 adult male Sprague-Dawley rats, the severed nerve was coapted to supraclavicular purely sensory nerves originating from C3 and C4 (sensory protection [SP] group). In another 10 Sprague-Dawley rats, the transected MC nerve was not protected by coaptation to sensory nerves (control group). After prolonged denervation or "sensory protection" (6 months), the MC nerve was then coapted in both groups to the purely motor medial pectoral nerve. Behavioral testing (grooming test) was performed on a weekly basis during the reinnervation time, which lasted 4 weeks. Statistically significant differences (p<0.05) favoring the SP group, were found at the second week of the reinnervation period, but not at the end of the experiment. Evaluation also included intraoperative electrical stimulation of the MC nerve, biceps muscle dry weights, motor endplate counts, and nerve axon counts of the MC nerve. The biceps muscle dry weights were statistically higher in the SP group, along with a trend for a higher number of motor endplates. No statistically significant difference was found in the nerve axon counts of the MC nerve between the two groups. Statistically better intraoperative electrical stimulation results were also encountered in the sensory protection group. An interpretation of the results favors the hypothesis that sensory reinnervation of a motor target may provide the necessary trophic environment to minimize muscle atrophy, until a motor donor nerve becomes available.

Animals↗

Distraction osteogenesis using IGF-I after nerve microreconstruction.

The discipline of limb lengthening has undergone numerous advances over the last few years. The neurologic complications surrounding this procedure are well established and described in the clinical setting, and can be deleterious for the patients in distraction osteogenesis protocols. The specific aims of the reported project were: 1) to determine the ability of IGF-I to enhance nerve regeneration in repaired nerves that are subjected to distraction only 4 weeks after nerve repair, and 2) to determine if a low dose of IGF-I applied at the time of the repair is neuroprotective to repaired nerves at this early time window. Forty adult male Sprague-Dawley rats were randomized into eight groups (n=5). Four groups (Groups A to D) underwent distraction of the femoral bone following sciatic nerve repair, and four groups served as controls (Groups E to H). Nerve reconstruction was achieved by end-to-end nerve repair (four groups, two with distraction [A, B] and two without [E, F]) and by interposition nerve grafting (four groups, two with distraction [C, D] and two without distraction [G, H]). A low dose of IGF-I was administered at the time of nerve microreconstruction. Distracted groups, despite the administration of IGF-I, demonstrated no signs of nerve regeneration, as assessed by sciatic functional index (SFI), electrophysiologic studies, and quantitative and qualitative histologic studies. Non-distracted groups showed signs of nerve regeneration. The 4-week time interval between nerve repair and distraction did not provide enough time for nerve regeneration to be completed, even if the repair was exposed to a low dose of IGF-1.

Anastomosis, Surgical↗

Outcomes of scapula stabilization in obstetrical brachial plexus palsy: a novel dynamic procedure for correction of the winged scapula.

Among the late consequences of obstetrical brachial plexus palsy is winging of the scapula, a functional and aesthetic deformity. This article introduces a novel surgical procedure for the dynamic correction of this clinical entity that involves the dynamic transfer of the contralateral trapezius muscle and/or rhomboid muscles and anchoring to the affected scapula. In more severe cases of scapula winging, the contralateral latissimus dorsi muscle may also need to be transferred to achieve dynamic scapula stabilization. The outcomes of this novel surgical procedure were analyzed in relation to the effect on abduction, external rotation, growth of the scapula, and distance of the scapula from the posterior midline. The results were analyzed in 26 patients who underwent this procedure and had adequate follow-up. The mean patient age was 6.39 years. Fourteen (54 percent) had a diagnosis of Erb palsy, and 12 (46 percent) had a diagnosis of global paralysis. All 26 patients had an additional secondary procedure performed prior to or simultaneously with the scapula stabilization procedure. In 19 patients, the contralateral trapezius was transferred and anchored to the medial border of the winged scapula alone, but in seven cases the underlying rhomboid major was transferred along with the trapezius muscle to provide sufficient scapula stabilization. In five cases in which the scapula winging was severe, the contralateral latissimus dorsi muscle was transferred at a second stage. After this procedure, all patients demonstrated improved scapula symmetry. The mean increase in abduction was 18 degrees (p < 0.001), the mean increase in external rotation was 19 degrees (p < 0.001), and the mean increase in anterior flexion was 12 degrees (p = 0.015). The improvement of the relative position of the winged scapula on the posterior thorax was analyzed by measuring the distance of the inferior angle of both scapulae from the midline, then calculating the difference between normal and affected sides and comparing this value before and after the scapula stabilization procedure. This value preoperatively was 3.24 cm; postoperatively it decreased to 0.36 cm (p < 0.001), demonstrating a statistically significant improvement.

Adolescent↗