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Biomedical subjects

Charles Kuntz

Publications and source records attributed to Charles Kuntz.

9 recordsLinked to original sources

Global expression of NGF promotes sympathetic axonal growth in CNS white matter but does not alter its parallel orientation.

Axonal regeneration is normally limited after injuries to CNS white matter. Infusion of neurotrophins has been successful in promoting regenerative growth through injured white matter but this growth generally fails to extend beyond the infusion site. These observations are consistent with a chemotropic effect of these factors on axonal growth and support the prevailing view that neurotrophin-induced axonal regeneration requires the use of gradients, i.e., gradually increasing neurotrophin levels along the target fiber tract. To examine the potential of global overexpression of neurotrophins to promote, and/or modify the orientation of, regenerative axonal growth within white matter, we grafted nerve growth factor (NGF) responsive neurons into the corpus callosum of transgenic mice overexpressing NGF throughout the CNS under control of the promoter for glial fibrillary acidic protein. One week later, glial fibrillary acidic protein and chondroitin sulfate proteoglycan immunoreactivity increased within injured white matter around the grafts. NGF levels were significantly higher in the brains of transgenic compared with non-transgenic mice and further elevated within injury sites compared with the homotypic region of the non-injured side. Although there was minimal outgrowth from neurons grafted into non-transgenic mice, extensive parallel axonal regeneration had occurred within the corpus callosum up to 1.5 mm beyond the astrogliotic scar (the site of maximum NGF expression) in transgenic mice. These results demonstrate that global overexpression of neurotrophins does not override the constraints limiting regenerative growth to parallel orientations and suggest that such factors need not be presented as positive gradients to promote axonal regeneration within white matter.

Animals↗

Vertebral osteomyelitis.

Vertebral osteomyelitis (VO) is an infectious disease of the vertebral body that requires early diagnosis with identification of the infecting organism to direct antibiotic therapy. Most VO can be treated nonsurgically, but 10% to 20% of cases require open surgical treatment. Excellent clinical outcomes can be achieved with appropriate medical and surgical treatment.

Anti-Bacterial Agents↗

Video-assisted thoracoscopic dissection of the brachial plexus: cadaveric study and illustrative case.

OBJECTIVE: Standard surgical approaches to the brachial plexus require an open operative technique with extensive soft tissue dissection. A transthoracic endoscopic approach using video-assisted thoracoscopic surgery (VATS) was studied as an alternative direct operative corridor to the proximal inferior brachial plexus. METHODS: VATS was used in cadaveric dissections to study the anatomic details of the brachial plexus at the thoracic apex. After placement of standard thoracoscopic ports, the thoracic apex was systematically dissected. The limitations of the VATS approach were defined before and after removal of the first rib. The technique was applied in a 22-year-old man with neurofibromatosis who presented with a large neurofibroma of the left T1 nerve root. RESULTS: The cadaveric study demonstrated that VATS allowed for a direct cephalad approach to the inferior brachial plexus. The C8 and T1 nerve roots as well as the lower trunk of the brachial plexus were safely identified and dissected. Removal of the first rib provided exposure of the entire lower trunk and proximal divisions. After the fundamental steps to the dissection were identified, the patient underwent a successful gross total resection of a left T1 neurofibroma with VATS. CONCLUSION: VATS provided an alternative surgical corridor to the proximal inferior brachial plexus and obviated the need for the extensive soft tissue dissection associated with the anterior supraclavicular and posterior subscapular approaches.

Adult↗

Vertebral column subtraction osteotomy for recurrent tethered cord syndrome in adults: a cadaveric study.

OBJECT: The standard treatment for lumbosacral tethered cord syndrome (TCS) in adults is surgical detethering. In patients with recurrent TCS, additional detethering operations are associated with increased risk of complications and subsequent scar formation. The authors studied the effect of undertaking a vertebral column subtraction osteotomy (VCSO) at the thoracolumbar junction to shorten the vertebral column and reduce neural element tension. METHODS: A model of TCS, developed in fresh-frozen human cadavers, was evaluated in three experiments. In Experiment 1, VCSO of 20 to 25 mm was performed at the T11-12 level. The vertebral column was sequentially shortened and the reduction in tension was measured separately in the terminal filum and the L-1 to S-3 or S-4 nerve roots. In Experiments 2 and 3 the reduction in tension was measured in the spinal cord after a VCSO and after simulating a traditional detethering operation. Vertebral column shortening produced tension reduction in all experiments. Tension decreased to less than 0.6 g in the terminal filum, L1-S3/4 nerve roots, and spinal cord after closure of a 20- to 25-mm VCSO. The mean +/- standard deviation of the deltatension/deltadistance was -0.242 +/- 0.019 g/mm for the terminal filum, -0.246 +/- 0.019 g/mm for the lumbar nerve roots, and -0.216 +/- 0.040 g/mm for the sacral nerve roots. A simulated traditional detethering operation required significant neural element release (detethering) to achieve spinal cord tension reduction equivalent to VCSO. CONCLUSIONS: A VCSO significantly reduced neural tension at the thoracolumbar junction. This novel procedure may provide an alternative to traditional surgical detethering when scarring is excessive and the risk of complications and retethering are high.

Adult↗

Disruption of the hyaluronan-based extracellular matrix in spinal cord promotes astrocyte proliferation.

Astrocyte proliferation is tightly controlled during development and in the adult nervous system. In the present study, we find that a high-molecular-weight (MW) form of the glycosaminoglycan hyaluronan (HA) is found in rat spinal cord tissue and becomes degraded soon after traumatic spinal cord injury. Newly synthesized HA accumulates in injured spinal cord as gliosis proceeds, such that high-MW HA becomes overabundant in the extracellular matrix surrounding glial scars after 1 month. Injection of hyaluronidase, which degrades HA, into normal spinal cord tissue results in increased numbers of glial fibrillary acidic protein (GFAP)-positive cells that also express the nuclear proliferation marker Ki-67, suggesting that HA degradation promotes astrocyte proliferation. In agreement with this observation, adding high- but not low-MW HA to proliferating astrocytes in vitro inhibits cell growth, while treating confluent, quiescent astrocyte cultures with hyaluronidase induces astrocyte proliferation. Collectively, these data indicate that high-MW HA maintains astrocytes in a state of quiescence, and that degradation of HA following CNS injury relieves growth inhibition, resulting in increased astrocyte proliferation.

Animals↗

Prospective evaluation of thoracic pedicle screw placement using fluoroscopic imaging.

BACKGROUND: In this prospective 18-month study, 29 patients underwent posterior thoracic instrumentation with placement of 209 transpedicular screws guided by intraoperative fluoroscopic imaging and anatomic landmarks. We assessed the safety, accuracy, complications, and early stability of this technique. METHODS: Pedicle and pedicle-rib units were measured, and screw cortical penetrations were graded on anatomy and depth of penetration. All 29 patients underwent preoperative computed tomographic (CT) imaging, and 28 underwent postoperative CT imaging (199/209 screws). RESULTS: From T2 to T12, screw diameters were >or=5 mm with mean medial screw angulation measuring 20-25 degree. Of the 209 screws placed from T1 to T12, 111 had diameters greater than or equal to the pedicle width. From T3 to T9, the mean diameter of the pedicle screws exceeded the mean pedicle width. Lateral pedicle wall penetration occurred significantly more often than superior, inferior, and medial pedicle wall penetrations and anterolateral vertebral body penetration. Five of six high-risk screw penetrations occurred in one patient when intraoperative technique was compromised. We observed no new postoperative neurologic deficits, visceral injuries, or pedicle screw instrumentation failures. The three high-risk anterolateral vertebral body penetrations at T1 and T2 were associated with a significantly decreased mean screw transverse angle; the three high-risk medial pedicle wall penetrations occurring from T3 to T9 were associated with a significantly increased mean screw transverse angle. Among all 26 patients available at postoperative follow-up (mean 11.9 months), the mean loss of kyphosis correction was 2.0 degree. CONCLUSIONS: Guided by intraoperative fluoroscopic imaging and anatomic landmarks, thoracic pedicle screws can be placed safely. Early clinical follow-up reveals excellent results with minimal loss of kyphosis correction.

Adult↗

Accuracy of thoracic vertebral body screw placement using standard fluoroscopy, fluoroscopic image guidance, and computed tomographic image guidance: a cadaver study.

STUDY DESIGN: A surgical simulation study in human cadaver spine specimens was conducted to evaluate the accuracy of thoracic vertebral body screw placement using four different intraoperative imaging techniques. OBJECTIVE: To compare standard fluoroscopy, fluoroscopy-based image guidance with two different referencing methods, and computed tomography-based image guidance by the measuring the time required for screw placement, the radiation exposure to specimen and surgeon, and the accuracy of screw position in the thoracic spine. SUMMARY OF BACKGROUND DATA: Image guidance provides additional anatomic information to the surgeon and may improve safety of technically difficult surgical procedures. The placement of screws in the thoracic spine is a technically demanding procedure in which inaccurate screw positioning places the spinal cord, nerve roots, and paraspinal structures such as the aorta and pleural space at risk for injury. Image-guided surgery may improve the accuracy of thoracic screw placement. METHODS: Using four different intraoperative imaging methods, two experienced surgeons placed 337 vertebral body screws through the pedicles of thoracic vertebrae in 20 human cadaver thoracic spine specimens. The specimens then were examined with radiographs, computed tomography, and anatomic dissection to determine screw position. Measurements included procedure setup and screw insertion time, radiation exposure to the specimen, the surgeon's hand, the surgeon's body, frequency, direction, and magnitude of screw perforation through the cortical margins of thoracic vertebrae. RESULTS: As compared with surgery using standard fluoroscopy, fluoroscopy-based image guidance that uses multiple reference marks and computed tomography-based image guidance improves the accuracy of thoracic vertebral body screws, but increases the time required for screw placement and the specimen radiation exposure. Exposure to radiation is minimal at the surgeon's body level and dependent on surgical technique at the surgeon's hand level. Screw perforation occurs most frequently in the lateral direction. CONCLUSIONS: Fluoroscopy-based image guidance that uses only a single reference marker for the entire thoracic spine is highly inaccurate and unsafe. Systems with registration based on the instrumented vertebrae provide more accurate placement of thoracic vertebral body screws than standard fluoroscopy, but expose the patient to more radiation and require more time for screw insertion.

Adult↗

An immunocompetent patient with primary Scedosporium apiospermum vertebral osteomyelitis.

Scedosporium apiospermum, the asexual anamorph of Pseudallescheria boydii, is a ubiquitous saprophytic fungus that usually causes cutaneous/subcutaneous infection but may manifest as an invasive disease, often in immunocompromised hosts. Following an extensive literature review, we think that this case represents the first documented report of a primary infection of the spine in an immunocompetent patient. Despite extensive surgical debridement and itraconazole therapy, the patient died of multisystem organ failure of unknown etiology. Our case and three previously reported cases of P. boydii vertebral osteomyelitis highlight the importance of obtaining repeat cultures in patients with culture-negative vertebral osteomyelitis who fail to adequately respond to empiric standard antibacterial and/or antimycobacterial therapy. Combined surgical debridement and antifungal therapy have been required for eradication of P. boydii spinal infections in two previously reported immunocompromised patients, although the optimal antifungal regimen for this infection has not been established.

Antifungal Agents↗