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Biomedical subjects

D F Kallmes

Publications and source records attributed to D F Kallmes.

At least 19 recordsLinked to original sources

A failure of matrix metalloproteinase inhibition in the prevention of rat intracranial aneurysm formation.

We tested the hypothesis that nonspecific matrix metalloproteinase (MMP) inhibition with doxycycline would decrease the incidence of intracranial aneurysm formation in a rat aneurysm model. We performed common carotid artery ligation on 96 Long-Evans rats. A treatment group of 48 animals was chosen at random to receive oral doxycycline (3 mg/kg) in addition to standard rat chow, and the control group of 48 animals received standard rat chow only. The major circle of Willis arteries was dissected at 1 year following carotid ligation, and the proportions of animals with aneurysms were compared between groups using Fisher's exact test. Four animals given oral doxycycline and ten control animals expired before 1 year. Of the examined animals, eight saccular intracranial aneurysms were found in 8 of 45 animals which had received doxycycline (17.8%) and seven saccular intracranial aneurysms were found in 7 of 37 control animals (18.9%). There was no significant difference in aneurysm formation between the doxycycline-treated and control groups (P=0.894). Nonspecific MMP inhibition with doxycycline is not effective in preventing intracranial aneurysm formation in a rat model.

Animals↗

A proposed ordinal scale for grading histology in elastase-induced, saccular aneurysms.

BACKGROUND AND PURPOSE: The elastase-induced aneurysm model in rabbits, though widely applied, still offers no quantitative or qualitative metric for histologic outcome. This study is aimed at producing such a scale to evaluate outcome and facilitate meaningful, preclinical comparison among devices proposed for aneurysm treatment. MATERIAL AND METHOD: Elastase-induced aneurysms were created and embolized in 30 rabbits. Aneurysms were harvested between 2 and 24 weeks. Specimens were embedded in paraffin, sectioned, and stained with hematoxylin and eosin. The scale comprised 3 subcategories: extent and degree of recanalization/coil compaction; neck healing, based on thickness and type of tissue across the neck; and dome healing. Neck healing was assessed by both gross and microscopic inspections. Compaction was assessed by using both the angiographic and histologic images. Dome healing was assessed by using the microscopic images only. Data were analyzed with either analysis of variance for the quantitative data or Kruskal-Wallis tests when analyzing the nonparametric data. RESULTS: We noted a significant main effect for healing over time (P = .0016). Post hoc tests showed that, at 2 weeks, the mean score was 1.4 +/- 0.8, as compared with a mean score of 7.2 +/- 1.6 for the 24-week time point (P < or = .05). Further, significant differences in healing between narrow-necked (6.0 +/- 1.3) and wide-necked aneurysms (3.5 +/- 1.1) were seen at 4 weeks (P = .0433). The dynamic range of the scale also appears to be appropriate, because there was adequate range at the upper portion of the scale to reflect improved healing that might be achieved with future devices. CONCLUSIONS: This scale is a potentially relevant outcome measurement tool for elastase-induced aneurysms after endovascular therapy. Future studies are still required to confirm its practical relevance.

Animals↗

Long-term patency of elastase-induced aneurysm model in rabbits.

BACKGROUND AND PURPOSE: Long-term patency in untreated experimental aneurysms represents a critical attribute of any system proposed for the testing of aneurysm occlusion devices. Our purpose was to evaluate the long-term patency in elastase-induced saccular aneurysm models in rabbits. METHODS: Serial intravenous digital subtractive angiography (IVDSA) was performed in 20 elastase-induced saccular aneurysm models in rabbits 1, 3, 6, 9, 12, and 24 months after creation. Aneurysm dimensions, including neck diameter, width, and height, were measured and calculated from IVDSA images. Comparisons of the aneurysm sizes across time were performed by using the paired Wilcoxon signed rank test and the Friedman test. RESULTS: None of the 20 aneurysms showed spontaneous thrombosis at any time point. Mean dimensions did not change over time for any parameter. Mean aneurysm neck, width, and height were not significantly changed at interval evaluations of 1, 3, 6, 9, 12, and 24 months (P = .210; P = .413, and P = .405, respectively). CONCLUSION: Long-term patency in elastase-induced saccular aneurysm models in rabbits is excellent. Aneurysm dimensions remain stable for as long as 2 years following creation.

Angiography, Digital Subtraction↗

New fractures after vertebroplasty: adjacent fractures occur significantly sooner.

BACKGROUND AND PURPOSE: Whether vertebroplasty increases the risk of adjacent-level vertebral fractures remains uncertain. Biomechanical and clinical studies suggest an increased risk, but compelling data have not yet been put forth to settle this difficult issue. We believe that an analysis of the time interval between vertebroplasty and subsequent fractures may shed additional light on this debate. We specifically hypothesized that subsequent fractures would occur sooner and more frequently in the vertebrae adjacent to the treated level. METHODS: We performed a retrospective analysis of the risk and timing of subsequent fractures in patients previously treated with vertebroplasty. Multiple linear regression was used to explore factors that influence the time to new fracture following vertebroplasty. Fractures were then divided on the basis of whether they occurred adjacent or non-adjacent to the treated level. Survival analysis was used to compare time to new fracture among the 2 groups, and the relative risk of both types of fracture was calculated. RESULTS: In this study, 186 new vertebral fractures occurred in 86 (19.9%) of 432 patients. Seventy-seven (41.4%) fractures were of vertebrae adjacent to the level treated with vertebroplasty. Median times until diagnosis of new adjacent and non-adjacent level fractures were 55 days and 127 days, respectively. Time to fracture was significantly different between the 2 groups (logrank <0.0001). Distance of the new fracture from the treated level was also significantly associated with time to new fracture (P < .0001). Relative risk of adjacent level fracture was 4.62 times that for non-adjacent level fracture. CONCLUSION: These data demonstrate an association between vertebroplasty and new vertebral fractures. Specifically, following vertebroplasty, patients are at increased risk of new-onset adjacent-level fractures and, when these fractures occur, they occur sooner than non-adjacent level fractures.

Adult↗

A longitudinal immunohistochemical study of the healing of experimental aneurysms after embolization with platinum coils.

BACKGROUND AND PURPOSE: The purpose of this study was to probe the cellular mechanism of healing in aneurysms after platinum coil embolization, by using multiple special stains and immunolabels. METHODS: Elastase-induced aneurysms were created and embolized in 28 rabbits. Aneurysms were excised between 2 and 24 weeks after embolization. Specimens were embedded in paraffin, sectioned, and stained with hematoxylin-eosin, Masson trichrome, and multiple immunostains. RESULTS: At 2 weeks, peripheral sparse spindle-nucleated cells were positive for alpha-smooth muscle actin (SMA), myosin, and vimentin, indicating myofibroblastic differentiation. At 4 weeks, all spindle-nucleated cells in the aneurysm were positive for SMA, myosin, desmin, and vimentin. Ten weeks after embolization, positive immunohistochemical staining in the cells populating the aneurysm significantly decreased. Mean positive SMA cells, per high-powered field were 5 +/- 3, 45 +/- 9, 10 +/- 5, 0 +/- 0, and 0 +/- 0 at 2, 4, 10, 16, and 24 weeks, respectively. Findings of a Kruskal-Wallis test showed these data to be significantly different (P =.0001). Post hoc tests revealed significantly greater amounts of SMA-positive staining in the cells at 4 weeks compared with those at 2, 10, 16, and 24 weeks (P < .05). In addition, the 10-week group had significantly more positive cells than the 16- and 24-week groups (P < .05). There was a 78% decrease in apoptotic cells between 4 (37 +/- 11) and 10 weeks (8 +/- 4) after implantation. Apoptotic cells were completely absent beyond 10 weeks. CONCLUSION: Aneurysm healing, in response to platinum coil embolization, appeared to progress through the stages of thrombus formation, granulated tissue organization, and loose connective tissue formation. Myofibroblasts, the key cellular component involved in healing, appeared within the aneurysm early. They progressively reduced in number with time and finally disappeared through the mechanism of apoptosis.

Animals↗

Radiation exposure to the primary operator during endovascular surgical neuroradiology procedures.

Endovascular surgical neuroradiologists can receive a substantial amount of occupational radiation exposure. We evaluated the amount of radiation exposure that results from the practice of performing hand injections during digital subtraction angiography (DSA). The primary operator can significantly decrease the radiation dose by leaving the room for DSA procedures. However, the total radiation dose for the primary operator is relatively low and is certainly within allowable regulatory limits when extrapolated to a yearly dose.

Angiography, Digital Subtraction↗

The radial artery access site for interventional neuroradiology procedures.

The radial artery access site offers many advantages in neuroangiography. Right vertebral artery access is readily obtained from a right radial artery approach. As with cardiology procedures, neuroradiology procedures may necessitate the use of lytic therapy or platelet inhibitors. Sheath removal can be done without reversal of anticoagulation or concerns about major bleeding complications. We report our experience in using the radial artery access site for interventional neuroradiology cases. Practical considerations and technical details are offered.

Aged↗

Does vertebroplasty cause incident vertebral fractures? A review of available data.

Vertebroplasty has been in practice in the United States for approximately 10 years and has been described as providing significant benefit to patients with painful vertebral compression fractures. Although the procedure appears to provide dramatic pain relief, it is not without complications. The primary point of discussion in this paper is whether vertebroplasty predisposes patients to the development of additional vertebral fractures, at a rate higher than that seen in the absence of vertebroplasty. To date there remains no definitive answer to this question. There is, however, a significant body of data available in the literature that relates to this issue. This review explores and attempts to synthesize the data both supporting and refuting a relationship between vertebroplasty and the development of subsequent fractures.

Fractures, Compression↗

Bovine aortic arch variant in humans: clarification of a common misnomer.

The term "bovine arch" is widely used to describe a common anatomic variant of the human aortic arch branching. This so-called bovine aortic arch has no resemblance to the bovine aortic arch. We describe the most common human aortic arch branching patterns and compare these with the bovine aortic arch.

Anatomy, Comparative↗

Subsequent vertebral fractures after vertebroplasty: association with intraosseous clefts.

BACKGROUND AND PURPOSE: Patients with vertebral fractures containing intraosseous clefts may represent a distinct subgroup of vertebroplasty patients, yet the development of subsequent vertebral fractures in this population has not been explored. We tested the hypothesis that after vertebroplasty for intraosseous clefts, subsequent fractures would occur earlier and more frequently than after treatment of non-cleft-containing fractures. METHODS: We retrospectively reviewed 362 patients treated with vertebroplasty for osteoporotic fractures. The location, frequency, and timing of subsequent fractures were compared between 2 subgroups: group 1, patients treated at fractures containing clefts, and group 2, treated patients without clefts. A vertebra-by-vertebra analysis was used to compare the relative risk and timing of subsequent fractures adjacent to vertebrae with or without clefts. RESULTS: Group 1 included 63 patients treated at 65 vertebrae and group 2 included 250 patients treated at 399 vertebrae. Group 1 demonstrated a nearly twofold increased risk of subsequent fracture (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.04-3.49, P = .037). At the vertebral level, the relative risk of subsequent fracture was 2.02 (95% CI, 1.46-2.58; P = .013) times greater adjacent to a treated cleft. Fractures adjacent to any treated level occurred significantly sooner than nonadjacent fracture (P = .0004). The presence of a cleft was not significantly associated with the timing of subsequent fractures. CONCLUSIONS: Patients with osteoporotic vertebral fractures containing clefts are at increased risk for subsequent fractures and treatment of these clefts is associated with increased rates of adjacent fracture. There is no significant difference in the timing of subsequent fractures based on the presence of a cleft.

Bone Cements↗

Can neck size in elastase-induced aneurysms be controlled? A retrospective study.

BACKGROUND AND PURPOSE: Reproducible animal models with appropriate neck size are crucial for preclinical assessment of aneurysm therapies. Our purpose was to determine whether the neck size of elastase-induced aneurysms could be controlled by adjusting the position of the temporary occlusion balloon. METHODS: Seventy-two elastase-induced aneurysms in rabbits were retrospectively analyzed. Three groups (group 1, n = 35; group 2, n = 32; group 3, n = 5) were defined according to different balloon position (lowest, intermediate, and highest, respectively) related to the origin of right common carotid artery (CCA). Aneurysm sizes in different groups were measured and compared; parent artery dilation was assessed as present or absent. The Wilcoxon rank sum test, the Fisher exact test, and the chi(2) test were used for statistics process. RESULTS: The mean aneurysm neck diameter in group 1 was significantly wider than that in group 2 (P = .0001). The proportion of wide-necked (diameter of neck >4 mm) aneurysms in group 1 was significantly higher than that in group 2 (P = .0011). The mean dome/neck ratio in group 1 was smaller than that of group 2 (P = .0031). Aneurysm width and height and the frequency of parent artery dilation were not different in groups 1 and 2 (P = .43, P = .10, and P = .25). No aneurysms formed in group 3. CONCLUSION: The neck size of elastase-induced aneurysms can be controlled by adjusting the position of the inflated balloon, with balloon positioning that bridges from the CCA to the subclavian/brachiocephalic arteries yielding narrow-necked aneurysms.

Aneurysm↗

Intra-arterial digital subtraction angiography through the ear artery for experimental aneurysm imaging.

Digital subtraction angiography through the central artery of the ear was performed to show elastase-induced aneurysms in 34 rabbits. Twenty-eight (82%) aneurysms in which common origins of the bilateral common carotid artery (CCA) were found were well shown. All 6 other aneurysms not well shown had separate origins of the CCAs from the aortic arch (P < .001). This method can be used for angiographic follow-up when there is a common origin of the CCAs.

Angiography, Digital Subtraction↗

Acute vertebral compression fractures in patients with multiple myeloma: evaluation of vertebral body edema patterns on MR imaging and the implications for vertebroplasty.

The presence of edema on MR imaging is a common finding in acute or subacute vertebral body compression fractures. Compression fractures can present in patients with benign osteoporosis, metastases, multiple myeloma, or hemangiomas. We present 2 patients with multiple myeloma who had symptomatic acute and subacute compression fractures documented on imaging studies without associated edema on MR imaging evaluation.

Bone Cements↗

The effects of cement volume on clinical outcomes of percutaneous vertebroplasty.

BACKGROUND AND PURPOSE: There exists significant variability in the volume of polymethylmethacrylate cement injected during percutaneous vertebroplasty. Larger cement volumes injected may be associated with better clinical outcomes, but larger volumes may also be associated with greater risk of complications related to cement leakage. We describe an analysis of the association between clinical and procedural variables, including cement volume injected, and the clinical outcomes of patients treated with single-level vertebroplasty. METHODS: Retrospective analysis of 158 patients treated with single-level vertebroplasty was performed. Relationships among patient and procedural variables and relationships between these variables and ordinal clinical outcome scores of pain and medication use at postprocedure time points from 1 week to 2 years were evaluated with bivariate and multivariable analyses. RESULTS: There was no significant association between the volume of cement injected and the clinical outcomes of postprocedure pain (P = .159-.871) and medication use (P = .223-.875). CONCLUSION: Vertebroplasty operators need not feel compelled to achieve particular cement volumes injected in the pursuit of better clinical outcomes but should strive to achieve the maximal safe filling of individual vertebral bodies.

Adult↗

Morphologic analysis of BMP-9 gene therapy-induced osteogenesis.

The present study was performed to determine the histological, ultrastructural, and radiographic changes that occur over time at intramuscular BMP-9 gene therapy treatment sites. Several members of the bone morphogenetic protein (BMP) family have the potential to induce osteochondrogenesis when the protein is delivered to rodents, canines, rabbits, and nonhuman primates. Previous studies have also demonstrated that BMP gene therapy utilizing adenoviral vectors can also stimulate orthotopic and heterotopic bone formation in rodents and rabbits. Athymic nude and Sprague-Dawley rats were injected with Ad-BMP-9 or Ad-beta-Gal (3.75 x 10(9) particles) in their thigh musculature and light microscopic, electron microscopic, and computerized tomography analysis was performed 3, 6, 9, 12, 15, 18, 21, and 100 days later. To assess early mesenchymal cell proliferation, a bromodeoxyuridine (BrdU) immunohistochemical analysis was also performed 48, 60, and 72 hr postinjection in athymic nude rats. All animals demonstrated extensive endochondral bone formation at the Ad-BMP-9 treatment sites within 3 weeks. The Sprague-Dawley rats also exhibited a massive, acute inflammatory infiltrate during the first week. Proliferating mesenchymal stem cells were clearly evident as early as 2 days after treatment, which differentiated into small or hypertrophied chondrocytes during the next week. During the third week, the cartilaginous matrix mineralized and formed woven bone, which converted to lamellar bone by 3 months. No evidence of bone formation was demonstrated at the Ad-beta-Gal injection sites in the athymic nude or Sprague-Dawley rats. In addition, no cellular proliferation was seen at the Ad-beta-Gal treatment sites in the athymic nude animals as assessed by light microscopy and BrdU immunohistochemistry. The extensive bone formation induced by Ad-BMP-9 suggests that BMP gene therapy may have potential utility in the treatment of degenerative, rheumatic, or traumatic bone pathology.

Adenoviridae↗

Dr. Gary J. Becker young investigator award: comparison of small-diameter type 1 collagen stent-grafts and PTFE stent-grafts in a canine model--work in progress.

PURPOSE: To report an in-progress experiment in a canine model in which two types of small-diameter stent-grafts-one constructed of polytetrafluoroethylene (PTFE) and the other of a new, type 1 collagen material-were compared regarding vessel patency, intimal hyperplasia formation, and tissue reaction. MATERIALS AND METHODS: Six mongrel dogs weighing 30-35 kg were used. Stent-grafts of 4-mm diameter and 20-mm length were constructed with use of balloon-expandable stainless-steel stents wrapped with either PTFE or a new type 1 collagen graft. Stent-grafts were placed in deep femoral arteries bilaterally (PTFE on one side, collagen on the other). Animals were followed for 2 weeks (n = 2), 6 weeks (n = 2), or 12 weeks (n = 2). Percent stenosis based on angiographic findings as well as thickness and area of neointimal hyperplasia were compared at each time point and compared with use of the Student t test. RESULTS: All devices were patent in the immediate postimplantation period. Five of six collagen stent-grafts and five of six PTFE implants were patent at follow-up. In-stent stenosis was undetectable angiographically in all five patent collagen stent-grafts. All five patent PTFE stent-grafts showed demonstrable in-stent stenosis (10%-60%), indicating a trend toward improved patency in collagen stent-grafts versus PTFE stent-grafts (P = .07). Neointimal hyperplasia was absent at 2 weeks in the collagen stent-grafts. Neointimal thickness increased to a maximum of 360 microm at 12 weeks in the collagen stent-grafts. For PTFE stent-grafts, neointimal hyperplasia was present in all samples and reached a maximum of 770 microm at 12 weeks (P = .03). CONCLUSIONS: Even in small-diameter vessels, type 1 collagen stent-grafts demonstrate excellent patency rates and favorable histologic findings. The type 1 collagen stent-graft technology merits further developmental efforts in preclinical models.

Animals↗

Preliminary reports and the rates of publication of follow-up reports in peer-reviewed, indexed journals.

PURPOSE: To test the hypothesis that articles published as "preliminary" or "pilot" reports are followed by more definitive publications in only a minority of cases. METHOD: A survey of Medline was performed for reports published in 1992 in journals listed in the Abridged Index Medicus that had the word "preliminary" or "pilot" in the title. For identified reports, a Medline search of publications in 1992 through 1999 was performed, using lead author's name, second author's name, and senior (last) author's name, and at least one keyword based on the publication title. Preliminary and pilot publications were subdivided by type of study (controlled clinical study, case series, laboratory or nonclinical) and by the report of either positive or negative results. Rates of publication based on study design and publication bias were compared using the chi-square test for statistical significance. RESULTS: The rate of publication of follow-up reports within seven years of the initial publication was 27%. Follow-up studies of controlled clinical studies (40%) were published more frequently than were those of laboratory or nonclinical studies (31%) or case series (22%), but these differences were not significant (p >.10). There was no statistically significant difference in follow-up publication rates based on publication bias. CONCLUSION: Only 27% of studies published as preliminary or pilot reports were subsequently followed by a more definitive publication. While the words preliminary and pilot suggest that publication of further, refined work is pending, this is often not the case.

Bibliometrics↗