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Biomedical subjects

D F Kallmes

Publications and source records attributed to D F Kallmes.

At least 37 records · Page 2Linked to original sources
PubMed2001

Transforming growth factor beta-coated platinum coils for endovascular treatment of aneurysms: an animal study.

OBJECTIVE: To test the hypothesis that coating platinum coils with transforming growth factor beta (TGFbeta) would improve the cellular proliferation within experimental aneurysms relative to uncoated coils. MATERIALS AND METHODS: Elastase-induced saccular aneurysms were created in 12 New Zealand White rabbits. These aneurysms were embolized with platinum coils, either "control" (unmodified) coils or "test" (coated with TGFbeta) coils. Subjects were killed either 2 weeks (n = 3, control; n = 3, test) or 6 weeks (n = 3, control; n = 3, test) after embolization. Aneurysm tissue was embedded in plastic, sectioned, and stained with hematoxylin and eosin. The thickness of tissue covering the coils at the coil-lumen interface was measured by use of a digital microscope, and was compared between groups by use of the Student's t test (P < or = 0.05). RESULTS: Two-week implantation samples demonstrated mean thickness of tissue overlying TGFbeta-coated coils of 36+/-15 microm and mean thickness of overlying control coils of 3+/-5 microm, indicating significantly thicker tissue growth covering test versus control coils (P = 0.02). Six-week implantation samples demonstrated mean thickness of tissue overlying TGFbeta-coated coils of 86+/-74 microm versus mean thickness overlying control coils of 37+/-6 mu; this difference did not reach statistical significance (P = 0.30). Thickness of tissue covering TGFbeta-coated coils did not change significantly from 2 to 6 weeks (P = 0.31). Tissue thickness over control coils increased significantly between 2 and 6 weeks (P = 0.002). CONCLUSION: TGFbeta-coated platinum coils undergo earlier cellular coverage than standard platinum coils, but differences in coverage between coated and control coils are no longer present at later time points. These data suggest that improvements in intra-aneurysmal cellular proliferation resulting from coil modifications, although significant in the early postembolization phase, may dissipate over time.

Animals↗
PubMed2001

Suppression of cerebrospinal fluid and blood flow artifacts in FLAIR MR imaging with a single-slab three-dimensional pulse sequence: initial experience.

The authors compared high-signal-intensity flow-related artifacts present with a conventional two-dimensional (2D) fluid-attenuated inversion recovery (FLAIR) sequence with those seen with a single-slab, three-dimensional (3D) FLAIR sequence. Four readers graded the subarachnoid space and intraventricular artifacts, the pulsation artifacts, and the conspicuity of cranial nerves in the posterior fossa. For all comparisons, differences between 2D and 3D images were highly statistically significant, with 3D imaging being superior in all cases.

Adult↗
PubMed2001

In vitro effects of transcatheter injection on structure, cell viability, and cell metabolism in fibroblast-impregnated alginate microspheres.

PURPOSE: To determine if microsphere-encapsulated cell preparations can be delivered through a microcatheter without compromising microsphere structure, cell viability, or metabolism. MATERIALS AND METHODS: Fibroblast-impregnated microspheres were fabricated by using 1.0% alginate and rabbit synovial fibroblasts. Fibroblast-impregnated alginate microspheres injected through microcatheters were analyzed in parallel with identical noninjected microspheres. The effects of transcatheter injection on structure and cell viability (percentage of viable cells per microsphere) were correlated with microsphere size. Structural effects were analyzed by using light microscopy, and 7-day percentage (ratio of live cells to dead cells) cell viability was assessed with confocal microscopy and fluorescent staining. In a second series of experiments, the metabolism of small microspheres was studied during a course of 7 days by using a spectrophotometric bioanalyzer. RESULTS: Transcatheter injection caused fracturing and/or fragmentation of large (800-1,000 microm) and medium (500-750 microm) microspheres, while small (250-400 microm) microspheres were structurally unaffected by transcatheter injection. Fracturing and fragmentation were associated with cell release from the alginate matrix. Although transcatheter injection reduced cell viability by 17%-23% in all size categories, it did not cause a detectable alteration in the rate of glucose metabolism. CONCLUSION: Transcatheter injection was physiologically well tolerated by fibroblasts encapsulated in alginate microspheres; however, when microsphere diameter exceeded the catheter diameter, fracturing and fragmentation of microspheres compromised the sequestration function of the microsphere vector.

Alginates↗
PubMed2001

A light and electron microscopic study of ectopic tendon and ligament formation induced by bone morphogenetic protein-13 adenoviral gene therapy.

OBJECT: Bone morphogenetic proteins (BMPs) are involved in the growth and development of many tissues, but it is their role in skeletal development and their unique ability to induce ectopic and orthotopic osteogenesis that have attracted the greatest interest. Expression of the BMP-13 gene is predominantly localized to hypertrophic chondrocytes in regions of endochondral bone formation during development, as well as in mature articular cartilage in the adult. In addition, the application of BMP-13 on a collagen carrier induces neotendon/neoligament formation when delivered subcutaneously or intramuscularly in rodents. The aim of the present study was to determine the histological and ultrastructural changes that occur after the intramuscular injection of a first-generation BMP-13 adenoviral vector. METHODS: Athymic nude rats were injected with 3.75 x 10(10) plaque-forming units of adenovirus (Ad)-BMP-13 or Ad-beta-galactosidase in the thigh musculature, and the region was examined using light and electron microscopy at various time points between 2 days and 100 days postinjection. As early as 2 days after injection of Ad-BMP-13, progenitor cells were observed infiltrating between the transduced muscle fibers. These cells subsequently proliferated, differentiated, and secreted large amounts of collagenous extracellular matrix. By 100 days postinjection, the treated tissue displayed the histological and ultrastructural appearance of neotendon/neoligament, which was clearly demarcated from the surrounding muscle. Small foci of bone and fibrocartilage were also seen within the treated tissue. A short-term bromodeoxyuridine study also demonstrated rapid mesenchymal cell proliferation at the Ad-BMP-13 injection site as early as 48 hours postinjection. At all time points, the control AD-beta-gal injection sites were found to contain only normal muscle, without evidence of inflammation or mesenchymal cell proliferation. CONCLUSIONS: The results of this study indicate that in the future the use of the BMP-13 gene may have therapeutic utility for the healing of tendon and ligament tears and avulsion injuries.

Adenoviridae↗
PubMed2001

Serial angiography in an elastase-induced aneurysm model in rabbits: evidence for progressive aneurysm enlargement after creation.

BACKGROUND AND PURPOSE: Among the several reports of elastase-induced aneurysm models, only the rabbit common carotid artery (CCA) model has been used for testing endovascular occlusion devices. Our purpose was to study the growth characteristics of an elastase-induced aneurysm model in rabbits for the purpose of determining whether delayed aneurysm enlargement occurs after creation. METHODS: Nine New Zealand White rabbits (3-4 kg) were used in this study. All study animals underwent surgery to isolate the right CCA. In three control animals, the lumen was incubated with saline and iodinated contrast material for 20 minutes. In six test animals, the lumen of the CCA was incubated with porcine elastase for 20 minutes. In all study animals, the distal right CCA was ligated. IV digital subtraction angiography was performed on postprocedural days 3, 5, 7, 14, 28, 35, 56, 84, and 112. Using an external sizing reference, the width and height of patent arterial segments at the right CCA origin were measured by two observers. For test animals, aneurysm dimensions were compared between early and late time points by using the Student's t test. RESULTS: In the control (no elastase) animals, slitlike cavities at the origin of the right CCA decreased in size over time to become nearly obliterated by 21 days. Conversely, a short segment of the proximal CCA remained widely patent in all six test animals. With the exception of a single time point in one test animal, all "aneurysm" cavities in the test animals were dilated as compared with the normal diameter of the CCA. On day 3 after surgery, the mean width and height of the aneurysm cavities in the test animals were 3.2 +/- 0.6 and 6.0 +/- 1.3 mm, respectively. Compared with dimensions at day 3, aneurysms in test animals were larger at day 14, with mean width and height of 4.1 +/- 1.7 and 8.3 +/- 1.9 mm, respectively (P =.02). Aneurysms in test animals had increased further at 21 days compared with 14 days (P =.01). Compared with measurements obtained at 21 days, dimensions remained essentially unchanged at 28 and 35 days. Thirty-five days after surgery, mean width and height were 5.0 +/- 0.9 and 10.0 +/- 2.2 mm, respectively. Follow-up imaging performed < or = 4 months after aneurysm creation showed no further change in aneurysm dimensions. CONCLUSION: Elastase incubation and vessel ligation results in patent aneurysmally dilated arterial segments at the origin of the right CCA in rabbits. These aneurysms show progressive increases in diameter over time, finally stabilizing at approximately 1 month. Our data, which show early progressive aneurysm enlargement, suggest that this model may be used for the study of systemic therapies aimed at diminishing aneurysm rest regrowth and also indicate that embolization of these model aneurysms should be delayed at least 21 days after aneurysm creation.

Aneurysm↗
PubMed2001

Imaging of acute subarachnoid hemorrhage with a fluid-attenuated inversion recovery sequence in an animal model: comparison with non-contrast-enhanced CT.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery (FLAIR) MR imaging sequences have been previously described in the evaluation of acute subarachnoid hemorrhage (SAH) in human subjects and have demonstrated good sensitivity. The purpose of this study was to evaluate a FLAIR sequence in an animal model of SAH and to compare the results with those obtained with non-contrast-enhanced CT. METHODS: SAH was experimentally induced in 18 New Zealand rabbits by injecting autologous arterial blood into the subarachnoid space of the foramen magnum. Nine animals had high-volume (1-2 mL) injections, and nine animals had low-volume (0.2-0.5 mL) injections. Four control animals were injected with 0.5 mL of saline. The animals were imaged with a FLAIR sequence and standard CT 2-5 hours after injection. Gross pathologic evaluation of seven of the animals was performed. Four blinded readers independently evaluated the CT and FLAIR images for SAH and graded the probability of SAH on a scale of 1 to 5 (1 = no hemorrhage, 5 = definite hemorrhage). RESULTS: Overall, the sensitivity of FLAIR was 89%, and the sensitivity of CT was 39% (P <.01). In animals with a high volume of SAH, the sensitivity of FLAIR was 100%, and the sensitivity of CT was 56%. In animals with a low volume of SAH, the sensitivity of FLAIR was 78%, and the sensitivity of CT was 22%. The specificity of FLAIR in animals without SAH was 100%, and the specificity of CT was 100%. The average reader score for FLAIR was 3.8, and that for CT was 2.2 (P <.001). Reader scores for FLAIR were higher than those for CT in 94% (P <.01) of animals with SAH and in 25% of animals without SAH (P >.05). Seven animals underwent gross pathologic examination, and all had blood in the subarachnoid space around the brain stem. CONCLUSION: FLAIR was more sensitive than CT in the evaluation of acute SAH in this model, especially when a high volume of SAH was present. This study provides a model for further experimentation with MR imaging in the evaluation of SAH. These findings are consistent with those of current clinical literature, which show FLAIR to be an accurate MR sequence in the diagnosis of SAH.

Acute Disease↗
PubMed2000

Adjuvant use of epsilon-aminocaproic acid (Amicar) in the endovascular treatment of cranial arteriovenous fistulae.

We report our experience with the use of the antifibrinolytic agent epsilon-aminocaproic acid (EACA), Amicar, as an adjuvant to endovascular treatment of cranial arteriovenous fistulae. We also review applications of antifibrinolytic agents to neurovascular disorders and discuss the mechanism of action, dosing strategy, contraindications, and possible complications associated with the use of EACA. We identified 13 patients with cranial arteriovenous fistulae (five direct carotid cavernous fistulae [CCF], seven dural arteriovenous fistulae [DAVF], and one vein of Galen malformation) who received EACA as an adjunct to endovascular treatment. In all cases embolic coils were the primary embolic agent. We reviewed the modes of initial endovascular therapy and angiographic findings immediately thereafter and the response to EACA. Two direct CCF and two DAVF were completely thrombosed on follow-up angiography, and two DAVF demonstrated diminished flow after EACA therapy. Seven fistulae did not respond to EACA. Four of eight tightly coiled fistulae thrombosed, while none of five loosely coiled fistulae thrombosed. None of four cases with a residual fistula separate from the coil mass underwent thrombosis with EACA, while four of nine cases without a separate fistula thrombosed. There was no morbidity related to EACA therapy. EACA may thus be useful as an adjunct to endovascular treatment of cranial arteriovenous fistulae. Loose or incomplete coil packing of the fistula predicts a poor response to EACA therapy.

Adolescent↗
PubMed2000

Needle diameter in outpatient myelography: rates of adverse effects and current practice trends.

Telephone calls were made to 1251 consecutive patients one day following outpatient myelography. Data were available on 518 patients punctured with 22-gauge (g) (large-diameter) and 465 with 25-g (small-diameter) spinal needles. We surveyed 48 academic and private practice groups regarding needle diameter use in myelography; data were obtained from 34 private practice and 14 academic radiology departments. Patients reported adverse effects including mild and severe headache, back pain and nausea. The percentage of total adverse effects was significantly greater in the 22-g than in the 25-g needle group. The percentage of patients with headache was higher in the 22-g than in the 25-g group, but this difference was not statistically significant. Only 19% of private practice groups and 17% of academic centers use 25-g needles; the remainder use 20-g or 22-g needles.

Adult↗
PubMed2000

Osteocalcin-directed gene therapy for prostate-cancer bone metastasis.

Osteocalcin (OC) is a major noncollagenous bone protein whose expression is limited almost exclusively to osteotropic tumors and mature calcified tissue (differentiated osteoblasts). The function of OC, a highly conserved gamma-carboxyglutamic acid-containing protein, relies in part on its ability to bind hydroxyapatite and act as a chemoattractant for bone-resorbing cells. Serum osteocalcin levels are used clinically as an index of active bone turnover. Research in our laboratory has revealed that OC is expressed in several solid tumors, including osteosarcoma and ovarian, lung, brain, and prostate cancers. Evidence arising from reverse-transcription polymerase chain reaction (RT-PCR; detection of OC mRNA), immunohistochemical staining (detection of OC protein), and transient transfection and reporter assay (detection of OC mRNA transcription) reveals that OC expression is up-regulated in numerous solid tumors, with its expression being further elevated in androgen-independent prostate cancers. A recombinant, replication-defective adenovirus, Ad-OC-TK (OC promoter-driven herpes-simplex-virus thymidine kinase) was constructed and, when combined with the appropriate prodrug, either ganciclovir (GCV) or acyclovir (ACV), was found to be effective at destroying prostate-cancer cell lines in vitro and prostate tumor xenografts in vivo in both subcutaneous and bone sites. Additionally, via use of the OC promoter the supporting bone stromal cells are cotargeted when the prostate cancer interdigitates with bone stroma at the metastatic skeletal sites. Thus, maximal tissue-specific cell toxicity is achieved by the interruption of cellular communication between the prostate cancer and the bone stroma. We describe herein the preclinical foundation as well as the design and implementation of an ongoing phase I clinical trial at the University of Virginia that targets androgen-independent metastatic prostate cancer using the Ad-OC-TK vector.

Adenoviridae↗
PubMed2000

Retrograde venous perfusion with hypothermic saline and adenosine for protection of the ischemic spinal cord.

PURPOSE: Spinal cord injury and the resultant postoperative paraplegia are devastating complications of thoracic aortic surgery, for which no widely accepted protective interventions exist. We hypothesized that retrograde venous perfusion-cooling of the spinal cord with a hypothermic saline and adenosine solution would protect it from ischemic injury caused by thoracic aortic occlusion. METHODS: Adult domestic swine of either sex (weight range, 20 to 30 kg) were intubated and ventilated. A left thoracotomy was performed. The accessory hemiazygous vein was divided, and a catheter was inserted distally. The aorta was clamped at the left subclavian artery. The venous catheter was not used in the animals in the control group (n = 7); in the animals in the experimental group (n = 7), a cold (4 degrees C) saline and adenosine solution was infused into the accessory hemiazygous vein. After 30 minutes, the clamp and catheter were removed, and the chest was closed. A blinded observer evaluated the animals' hind-leg motor activity 24 hours later. The Tarlov scale was used: 0, complete paralysis; 1, minimal movement; 2, stands with assistance; 3, stands alone; 4, weak walk; 5, normal gait. The animals' rectal temperatures were measured at the end of the experiment, and blood pressure was measured throughout. Two other groups were studied to assess the effect of the intervention on spinal cord temperature. RESULTS: The animals in the control group had a mean Tarlov score of 1.7 +/- 0.6; the animals in the experimental group had a mean Tarlov score of 4.9 +/- 0.1 (P <.01). The animals in the experimental group had a significantly greater drop in spinal cord temperature than those in the control group (4. 05 +/- 0.6 degrees C vs 0.58 +/- 0.12 degrees C; P <.01). No significant difference in rectal temperatures was found, nor did any arrhythmias or hypotensive episodes occur in either group. Perfusion of the spinal cord was confirmed with angiography by using this approach. CONCLUSION: Retrograde venous perfusion-cooling of the spinal cord with a hypothermic saline and adenosine solution protects the cord from ischemic injury caused by clamping of the thoracic aorta.

Adenosine↗
PubMed2000

Bovine type I collagen as an endovascular stent-graft material: biocompatibility study in rabbits.

PURPOSE: To study the biocompatibility of a bovine type I collagen preparation as a material for small-vessel stent-grafts in rabbits. MATERIALS AND METHODS: A composite nitinol-collagen endovascular stent-graft with a 4-mm inner diameter was deployed in the abdominal aorta in nine rabbits. Angiography was performed, and the rabbits were sacrificed at 1, 2, and 7 days and at 1 and 3 months. The portion of the aorta containing the stent-graft was excised and was histologically evaluated. RESULTS: All stent-grafts were patent at all time points. On days 1, 2, and 7 after implantation, scattered red and white blood cells adhered to the stent-graft. At 1 month, the stent-graft was endothelialized and was infiltrated with fibroblasts that deposited collagen within the interstices of the implanted collagen material. At 3 months, there was additional collagen deposition within the interstices of the stent-graft that did not narrow the lumen of the stent-grafts. CONCLUSION: Type I collagen as a intravascular stent-graft material is biocompatible for at least 3 months in rabbits. It is rapidly endothelialized and does not cause reactive stenosis. As a versatile and biocompatible polymer, collagen is potentially useful in the construction of endovascular stent-grafts for use in human arteries.

Alloys↗
PubMed2000

1999 ARRS Executive Council Award. Creation of saccular aneurysms in the rabbit: a model suitable for testing endovascular devices. American Roentgen Ray Society.

OBJECTIVE: This study developed an animal model of intracranial aneurysms suitable for evaluating emerging endovascular devices for aneurysmal therapy. We characterized the short-, medium-, and long-term attributes of this endovascular technique for saccular aneurysmal creation in the rabbit. MATERIALS AND METHODS: The right common carotid artery was surgically exposed in nine New Zealand white rabbits. Using endovascular techniques, we occluded the origin of the right common carotid artery with a pliable balloon. Elastase was incubated endoluminally in the proximal common carotid artery above the balloon. The common carotid artery was ligated distally. Animals were studied angiographically and sacrificed at 2 weeks (n = 3), 10 weeks (n = 3), and 24 weeks (n = 3) after aneurysm creation. Histology was obtained. RESULTS: Saccular aneurysms formed in eight of the nine rabbits. The aneurysm projected from the apex of an approximately 90 degree curve of the parent vessel, the brachiocephalic artery. Mean aneurysm diameter was 4.5 mm (SD, 1.2 mm), and mean height was 7.5 mm (SD, 1.6 mm). All samples showed thinned elastic lamina and no evidence of inflammation. In four of eight aneurysms, unorganized thrombus was present in the dome of the aneurysm. CONCLUSION: Arterial aneurysms with intact endothelium and deficient elastic lamina were reliably created in an area of high shear stress in New Zealand white rabbits. Three of these aneurysms remained patent for at least 6 months. We found a simple procedure that can be readily applied to the testing of new endovascular devices for a reliable creation of aneurysms in rabbits.

Animals↗
PubMed2000

Comparison of patient age with MR imaging features of gangliogliomas.

OBJECTIVE: The purpose of this study was to compare MR imaging features of gangliogliomas in children less than 10 years old with those seen in patients at least 10 years old. MATERIALS AND METHODS: Our study population consisted of 15 female patients and 10 male patients with a mean age of 20 years. The early childhood group was composed of six children with a mean age of 5.5 years. The older group was composed of 19 patients with a mean age of 25.6 years. We assessed tumor volume, tumor location, percentage of tumor that was cystic, pattern of contrast enhancement, and degree of edema. RESULTS: The temporal lobe was the most common tumor location in both groups. Mean tumor volume in the early childhood group was 83 cm3, which was significantly larger than the mean tumor volume (9.78 cm3) for the older group (p = 0.001). Cystic tumors were more common in the early childhood group (83%) than in the older group (63%), and the average percentage of cysts in the cystic tumors was much higher in the early childhood group (67%) than in the older group (30%). Contrast enhancement was seen in five of six early childhood tumors and 13 of 16 tumors in older patients. Four of six tumors in the early childhood group and five of 19 tumors in the older patient group had associated edema. CONCLUSION: The mean tumor volume of gangliogliomas in the early childhood group was significantly larger than that of the older patient group. This finding may be indicative of differences in tumor growth patterns in the two groups, ability of the hemicranium to adjust to mass effect in childhood, or sampling error as a result of a relatively small sample size.

Adolescent↗
PubMed2000

Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent.

OBJECT: Bone morphogenetic proteins (BMPs) have been shown to have significant osteoinductive activity in numerous in vitro and in vivo assay systems, and BMP-2 and BMP-7 are currently being evaluated in human clinical studies. In the spinal region, BMPs have been shown to promote spinal arthrodesis at a higher rate than autologous bone alone. The delivery of BMPs via direct or ex vivo gene therapy techniques is also currently being evaluated and has shown promise in several mammalian models. The present study was designed to evaluate the efficacy of the use of direct, percutaneous BMP-9 adenoviral gene therapy to promote spinal fusion in the rodent. METHODS: Each animal was injected with 7.5x10(8) pfu of a BMP-9 adenoviral vector in the lumbar paraspinal musculature and allowed to survive 16 weeks. Computerized tomography studies and histological analysis demonstrated massive bone induction at the injection sites, clearly leading to solid spinal arthrodesis, without evidence of pseudarthroses, nerve root compression, or systemic side effects. CONCLUSIONS: The results of this study strongly support the advancement of BMP gene therapy techniques toward clinical use.

Adenoviridae↗
PubMed2000

Arterial dissections complicating cerebral angiography and cerebrovascular interventions.

BACKGROUND AND PURPOSE: Iatrogenic dissections are an uncommon complication of cerebral angiography. We retrospectively reviewed 12 cases of arterial dissections complicating cerebral angiography and cerebrovascular interventions to evaluate the clinical course of these dissections. METHODS: Cases from a large tertiary center performing a large number of neurovascular procedures were collected retrospectively. The patients' medical records and imaging studies were reviewed, with particular attention given to the cause of the dissection, the development of ischemic events resulting from the dissection, and the treatment used. RESULTS: Each of nine dissections affected a vertebral artery, each of two affected an internal carotid artery, and one affected a common carotid artery. The prevalence of iatrogenic dissections was 0.4%. Seven of the dissections were noted at the time of contrast material injection for the filming of cerebral angiograms. The other five dissections occurred during catheter or wire manipulations for interventional neuroradiologic procedures. Five of the patients in our series were treated with IV administered heparin for 24 to 48 hours. The other seven patients had recently suffered acute intracranial hemorrhage or undergone neurosurgery and could not undergo anticoagulant therapy. None of the patients developed symptoms of ischemia, but one was later found to have an asymptomatic infarct in the territory supplied by the dissected artery. CONCLUSION: Arterial dissections are an uncommon complication of cerebral angiography and cerebrovascular interventions and usually have a benign clinical course.

Adult↗
PubMed1999

In vivo endochondral bone formation using a bone morphogenetic protein 2 adenoviral vector.

Bone morphogenetic proteins (BMPs) are polypeptides that induce ectopic bone formation in standard rat in vivo assay systems. Previous studies have demonstrated the clinical utility of these proteins in spinal fusion, fracture healing, and prosthetic joint stabilization. Gene therapy is also a theoretically attractive technique to express BMPs clinically, since long-term, regulatable gene expression and systemic delivery with tissue-specific expression may be possible in future. This study was performed to determine whether an adenoviral vector containing the BMP-2 gene can be used to express BMP-2 in vitro and promote endochondral bone formation in vivo. In vitro, U87 MG cells transduced per cell with 20 MOI of an adenoviral construct containing the BMP-2 gene under the control of the universal CMV promoter (Ad-BMP-2) showed positive antibody staining for the BMP-2 protein at posttransfection day 2. The synthesis and secretion of active BMP-2 into the conditioned medium of Ad-BMP-2-transduced 293 cells were confirmed by Western blot analysis and the induction of alkaline phosphatase activity in a W-20 stromal cell assay. In vivo, Sprague-Dawley rats and athymic nude rats were injected with Ad-BMP-2 in the thigh musculature and were sacrificed on day 3, 6, 9, 12, 16, 21, 60, and 110 for histological analysis. The Sprague-Dawley rats showed evidence of acute inflammation, without ectopic bone formation, at the injection sites. In the athymic nude rats, BMP-2 gene therapy induced mesenchymal stem cell chemotaxis and proliferation, with subsequent differentiation to chondrocytes. The chondrocytes secreted a cartilaginous matrix, which then mineralized and was replaced by mature bone. This study demonstrates that a BMP-2 adenoviral vector can be utilized to produce BMP-2 by striated muscle cells in athymic nude rats, leading to endochondral bone formation. However, in immunocompetent animals the endochondral response is attenuated, secondary to the massive immune response elicited by the first-generation adenoviral construct.

Adenoviridae↗
PubMed1999

Percutaneous vertebroplasty in vertebral osteonecrosis (Kummell's spondylitis).

The authors report the clinical symptoms and response to therapy of a series of patients who presented with subacute or chronic back pain due to vertebral osteonecrosis (Kummell's spondylitis) and who underwent percutaneous vertebroplasty. The authors performed a retrospective chart review of a series of 95 patients in whom 149 painful, nonneoplastic compression fractures were demonstrated and who were treated with percutaneous transpediculate polymethylmethacrylate (PMMA) vertebroplasty. In six of these patients there was evidence of vertebral osteonecrosis, as evidenced by the presence of an intravertebral vacuum cleft on radiography or by intravertebral fluid on magnetic resonance (MR) imaging. Clinical and radiological findings on presentation were noted. Technical aspects of the vertebroplasty technique were compiled. Response to therapy, defined as qualitative change in pain severity and change in level of activity, was noted immediately following the procedure and at various periods on follow-up reviews. One man and five women, who ranged in age from 72 to 90 years (mean 81 years), were treated. Each patient had one compression fracture. The fractures were at T-11 (one patient), L-1 (two patients), L-3 (two patients), and L-4 (one patient). The pain pattern was described as severe and localized to the affected vertebra, and sometimes radiated along either flank. Pain duration ranged from 2 to 12 weeks, and the pain was refractory to conservative therapy that consisted of bedrest, analgesics, and external bracing. At the time of treatment, all patients were bedridden because of severe back pain. In all patients either plain radiographic or computerized tomography evidence of intravertebral vacuum cleft or MR imaging evidence of vertebral fluid collection consistent with avascular necrosis of the vertebral body was demonstrated. Four patients underwent bilateral transpediculate vertebroplasty, and two patients underwent unilateral transpediculate vertebroplasty. The fracture cavities were specifically targeted for PMMA injection. Additional fortification of the osteoporotic vertebral body trabeculae was also performed when feasible. "Cavitygrams" or intraosseous venograms with gentle contrast injection were obtained prior to application of cement mixture. In all patients subjective improvement in pain and increased mobility were demonstrated posttreatment. The follow-up period ranged from 4 to 24 hours after treatment. Two patients made additional office visits at 1 and 3 months, respectively. Patients presenting with vertebral osteonecrosis (Kummell's spondylitis) often suffer from local paraspinous or referred pain. When performing vertebroplasty on these patients, confirmation of entry into the fracture cavities with contrast-enhanced "cavitygrams" should be performed prior to injection of PMMA cement. The response to vertebroplasty with regard to amelioration of pain and improved mobility is encouraging.

Journal Article↗