Biomedical subjects

David W Cahill

Publications and source records attributed to David W Cahill.

7 recordsLinked to original sources

PubMed2003

Suitability of bioresorbable cages for anterior cervical fusion.

OBJECT: The authors conducted a pilot study to determine whether a bioresorbable intervertebral fusion device composed of 85/15 polylactide-polyglycolide (PLA-PGA) copolymer packed with bone autograft is a suitable alternative to promote arthrodesis after anterior cervical discectomy (ACD) in a caprine model. METHODS: The caprine cervical spine model has been used to evaluate interbody healing and fusion after application of bone grafts and instrumentation. Whether a bioresorbable device is suitable for facilitating intervertebral bone union has not been determined. Twelve goats underwent two-level ACD and fusion; eight received bioresorbable cages packed with autologous bone, and four received autologous bone alone. Goats were maintained without an orthosis and after 12 weeks underwent physical, radiographic, and histological evaluation. Cages had structurally degraded, and two had become extruded. Stable intervertebral union developed in three (19%) of 16 cage-implanted interspaces, and one (14%) of seven bone autograft-implanted interspaces; each was judged manually to be rigid (Grade 2), radiographically to be bridged by new osseous densities (Grade 2), and histologically to have marked new bone formation (Grade 3). A primarily fibrous union, however, stabilized the cage-implanted interspaces, and eight (50%) had developed a 4 to 6-mm foreign body granuloma. These interposed soft tissues were not present in the stable autologous bone-implanted interspace, which had successfully become fused. CONCLUSIONS: Interbody cages composed of 85/15 PLA-PGA copolymer contributed to a stable fibrous union, degraded. and produced granuloma after 12 weeks. Additional evaluations are necessary to determine whether other copolymer mixtures, or other bioresorbable materials, can contribute to an arthodesis without deleterious consequences.

Absorbable Implants↗

PubMed2002

Positive effect of transplantation of hNT neurons (NTera 2/D1 cell-line) in a model of familial amyotrophic lateral sclerosis.

Transplantation of hNT Neurons derived from the human teratocarcinoma cell-line (NTera2/D1) has been shown to ameliorate motor dysfunction in a number of injury or disease models in which the deficits are fairly localized. However, these cells have not been used before in a model with more extensive neurodegeneration. The aim of this study is to determine the effects of hNT Neuron transplants on motor neuron function in a mouse model of familial amyotrophic lateral sclerosis (FALS) in which there is a substitution of Alanine for Glycine at position 93 of the human SOD1 gene (G93A). Amyotrophic lateral sclerosis is a fatal degenerative motor neuron disease affecting the spinal cord, brainstem, and cortex. This disease clinically manifests as progressive muscular weakness and atrophy, leading to paralysis and death within 3-5 years of diagnosis. The FALS represents 10-13% of all cases. A range of behavioral tests was used to examine spontaneous locomotor activity, coordination, and muscle strength of mice. Long-term (10-11 weeks) transplantation of hNT Neurons into the L(4)-L(5) segments of the ventral horn spinal cord of FALS(G93A) mice at 7 weeks of age (before onset of overt behavioral symptoms of disease) delayed the onset of motor dysfunction for at least 3 weeks. The average lifespan of the transplanted mice was 128 days compared to 106 days for media-injected group. The last mouse in the hNT Neuron transplanted group was euthanized at 135 days of age when it display partial paralysis of the hindlimbs. Immunohistochemical analysis of the implanted spinal cords demonstrated the survival of grafted hNT Neurons and showed many healthy-appearing motor neurons near the implant site. These results suggest that hNT Neuron transplantation may be a promising therapeutic strategy for ALS.

Amyotrophic Lateral Sclerosis↗

PubMed2002

Effects of middle cerebral artery occlusion on spontaneous activity and cognitive function in rats.

The middle cerebral artery occlusion (MCAO) in the rat is a commonly used model to evaluate new therapeutic strategies for the treatment of ischemic stroke. However, many such studies rely on short-term neurological examination and infarct volume as endpoint measures while neglecting more long-term functional assessments. In this study, we examined whether there were changes in passive avoidance behavior, spontaneous behavioral patterns across the light-dark cycle, and motor coordination as measured on the rotorod test 1 month after Sprague-Dawley rats had undergone MCAO. Compared to age-matched controls, fewer animals in the MCAO group remained on the platform during the passive avoidance retention test (p < .03). Significant differences between the groups were observed in the spontaneous activity during the initial portions of both the light and dark testing periods, when the test situation was new (p < .01 to .05, depending on the variable examined). Any differences on the rotorod test failed to gain statistical significance. These results suggest that at least the passive avoidance test and measures of spontaneous activity are sensitive to ischemia-induced damage over a more prolonged survival period and therefore may be appropriate measures for long-term effectiveness of new treatments.

Animals↗

PubMed2002

Novel cellular approaches to repair of neurodegenerative disease: from Sertoli cells to umbilical cord blood stem cells.

Neural transplantation is a promising approach to the treatment of neurodegenerative diseases and brain injury that has been shown to be efficacious in many animal models. However, the use of fetal tissue limits the acceptability and widespread application of this technique. In this review we discuss possible alternative cell sources that may be used to repair the brain and spinal cord, with a focus on Sertoli cells, hNT Neurons, bone marrow and umbilical cord blood derived stem cells.

Journal Article↗

PubMed2002

Increased pedicle screw pullout strength with vertebroplasty augmentation in osteoporotic spines.

OBJECT: The authors conducted a biomechanical study to evaluate pedicle screw pullout strength in osteoporotic cadaveric spines. Nonaugmented hemivertebrae were compared with pressurized polymethylmethacrylate (PMMA)-augmented hemivertebrae. METHODS: Six formalin-fixed cadaveric thoracolumbar spines at least two standard deviations below the mean bone mineral density (BMD) for age were obtained. Radiographic and BMD studies were correlated to grades I, II, and III osteoporosis according to the Jekei scale. Each of the 21 vertebrae underwent fluoroscopic placement of 6-mm transpedicular screws with each hemivertebra serving as the control for the contralateral PMMA-augmented hemivertebra. Pedicle screws were then evaluated for biomechanical axial pullout resistance. Augmented hemivertebrae axial pullout forces were increased (p = 0.0005). The mean increase in pullout force was 181% for Grade I, 206% for Grade II, and 213% for Grade III osteoporotic spines. Augmented Grade I osteoporotic spines demonstrated axial pullout forces near those levels reported in the literature for nonosteoporotic specimens. Augmented Grade II osteoporotic specimens demonstrated increases to levels found in nonaugmented vertebrae with low-normal BMD. Augmented Grade III osteoporotic specimens had increases to levels equal to those found in nonaugmented Grade I vertebrae. CONCLUSIONS: Augmentation of osteoporotic vertebrae in PMMA-assisted vertebroplasty can significantly increase pedicle screw pullout forces to levels exceeding the strength of cortical bone. The maximum attainable force appears to be twice the pullout force of the nonaugmented pedicle screw for each osteoporotic grade.

Biomechanical Phenomena↗

PubMed2002

Functional recovery after complete contusion injury to the spinal cord and transplantation of human neuroteratocarcinoma neurons in rats.

OBJECT: Human neuroteratocarcinoma (hNT)-derived neurons are differentiated postmitotic neurons derived from a human teratocarcinoma cell line following treatment with retinoic acid. In preclinical transplantation studies investigators have demonstrated both their safety as a source of neurons for transplantation and efficacy in treating stroke-related behavioral deficits. The objective of this study was to examine whether hNT neurons transplanted in an area of complete spinal cord contusion would improve electrophysiological measures of spinal cord function. METHODS: Complete spinal cord contusion injury, defined as the complete loss of motor evoked potentials (MEPs), was produced in 30 rats at T-8. Ten rats with contused spinal cords underwent transplantation with hNT neurons within the site of contusion immediately after injury (immediate transplant group). Ten rats underwent hNT neuron transplantation following a 2-week evaluation for loss of MEPs (delayed transplant group). Ten other rats with contusion injury served as a spinal cord injury control group, and 10 rats underwent only a T-8 laminectomy and served as non-injured controls. All rats survived 8 weeks after transplantation. In the delayed transplant group significant functional recovery was observed, as demonstrated by return of MEPs and a modest improvement of motor function. Immunohistochemical analysis showed the survival, integration, and long fiber outgrowth of the grafted hNT neurons. CONCLUSIONS: These findings suggest that the transplantation of the hNT neurons may be an effective means of reestablishing electrical connectivity of the injured spinal cord.

Animals↗

PubMed2002

Cranial settling.

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Cervical Vertebrae↗