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Biomedical subjects

K G Harris

Publications and source records attributed to K G Harris.

12 recordsLinked to original sources

Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases.

Cellular DNA damage causes stabilization and activation of the tumor suppressor and transcription factor p53, in part by promoting multiple covalent modifications of the p53 protein, including acetylation. We investigated the importance of acetylation in p53 function and the mechanism by which acetylation influences p53 activity. Acetylation site substitutions reduced p53-dependent transcriptional induction and G1 cell cycle arrest. Chromatin immunoprecipitation analysis of the endogenous p21 promoter showed increased association of p53, coactivators (CBP and TRRAP), and acetylated histones following cell irradiation. Results with acetylation-defective p53 demonstrate that the critical function of acetylation is not to increase the DNA binding affinity of p53 but rather to promote coactivator recruitment and histone acetylation. Therefore, we propose that an acetylation cascade consisting of p53 acetylation-dependent recruitment of coactivators/HATs is crucial for p53 function.

Acetylation↗

Cranial osteomyelitis: diagnosis and follow-up with In-111 white blood cell and Tc-99m methylene diphosphonate bone SPECT, CT, and MR imaging.

PURPOSE: To assess the usefulness of indium-111 white blood cell and technetium-99m methylene diphosphonate bone single photon emission computed tomography (SPECT), computed tomography (CT), and magnetic resonance (MR) imaging in cranial osteomyelitis. MATERIALS AND METHODS: Twenty-six cases (25 patients: 13 male, 12 female; mean age, 55 years) of suspected osteomyelitis were evaluated. Sixteen were postoperative. Final diagnosis was established by means of bone culture in 18 cases and clinical follow-up in eight. RESULTS: Of 35 CT scans, 10 were true-positive (TP); three false-negative (FN); 13, true-negative (TN); one, false-positive (FP); and eight, equivocal. Of 36 SPECT scans, 19 were TP; 13, TN; one, FP; one, FN; and two, equivocal. Of 11 MR images four were TP; five, TN; and two, FN. CONCLUSION: CT is best for differentiation between soft-tissue and bone infection. MR imaging is best for assessment of the calvaria and skull base. SPECT is best for assessment of altered bone and may be the best technique for follow-up.

Adolescent↗

Spinal motion after cervical fusion. In vivo assessment with roentgen stereophotogrammetry.

STUDY DESIGN: A roentgen stereophotogrammetric (RS) technique using metallic markers was used to determine in vivo three-dimensional (3-D) motion data in the post-operative cervical spine. Two patients were examined with RS following fusion for up to 12 months at scheduled intervals. OBJECTIVES: The study was designed to develop a technique and provide an in vivo assessment of the fusion process following surgery. Besides the researchers and surgeons, this type of information is of particular interest to the FDA and implant manufacturers. SUMMARY OF BACKGROUND DATA: The high accuracy of the roentgen stereophotogrammetric (RS) technique using metallic markers to predict displacements across body joints, including spinal joints, has been well established in the literature. Its applications in the lumbar region to assess the fusion process as a function of time following surgery have also been reported. Similar in vivo applications (and results) dealing with the cervical region are lacking. METHODS: A roentgen stereophotogrammetric (RS) technique using metallic markers was developed. Appropriate in vitro studies were undertaken to assess its accuracy for in vivo applications in the cervical spine region. Following this, three Vitallium beads were surgically implanted in anatomically appropriate positions in of each the exposed vertebrae of two patients at the time of surgery. The patients were followed with RS serially for 12 months after surgery at scheduled intervals. At each RS session, roentgen stereo pairs of the cervical spine in neutral, maximum voluntary flexion, and maximum voluntary extension were obtained using a biplanar radiographic system. The metallic beads on the radiographs were digitized using an in-house software package to determine vertebral motions across the fused segments. RESULTS: In patient 1 (atlantoaxial fusion), the flexion-extension range of rotational motion decreased with time while the corresponding AP translation at the fusion level increased from 6 mm at 3 months post-op to 13 mm at 6 and 12 months postoperatively. The abnormal AP translation at 6 months and beyond was evident on extension/extension lateral radiographs, but the AP translation at 3 months was not visually evident. In patient 2 (anterior discectomy and interbody fusion), motions of small magnitude were observed at the fused level in all three axes. These motions actually increased over the one year observation period, but were never large enough to be visually detectable on lateral extension/extension radiographs. Patient 2 had a good clinical result despite these small motions. CONCLUSIONS: Roentgen stereophotogrammetry may detect motion in the in vivo cervical spine with a sensitivity heretofore unavailable. In patient 1, we were able to detect motion before it was visually manifest. In patient 2, small motions were detected at the level of a successful anterior cervical fusion, the significance of which remain uncertain.

Atlanto-Axial Joint↗

Intracranial vasculitis.

The etiology and types of intracranial vasculitis are described, along with a neuroimaging-oriented classification system. Specific entities are discussed in detail. The role of various modalities is defined, as well as a practical approach to diagnosis.

Adult↗

Diagnosing intracranial vasculitis: the roles of MR and angiography.

PURPOSE: To describe our experience with MR and angiography in diagnosing intracranial vasculitis and to test the hypothesis that MR can be used to screen for patients unlikely to have vasculitis. METHODS: Ninety-two patients who had angiography with "exclude vasculitis" as the indication or who had angiography and a clinical diagnosis of vasculitis were identified. Angiograms of all 92 patients and the MRs of the 70 patients who had both studies were reviewed. RESULTS: Eleven patients had intracranial vasculitis. Angiography showed characteristic changes in 8. MR, performed in 9 of 11 vasculitis cases, was significantly abnormal in all 9. Among 70 patients who had both studies, 19 had MR that was completely normal or showed only incidental findings. None of these 19 was diagnosed with vasculitis. The diagnostic yield of angiography performed to exclude vasculitis was only 6%. CONCLUSIONS: Evaluation for intracranial vasculitis should include MR. A negative MR excludes intracranial vasculitis more definitively than does a negative angiogram and makes the likelihood of finding vasculitis with angiography negligible.

Adolescent↗

In vivo kinematics of the cervical spine. Part I: Development of a roentgen stereophotogrammetric technique using metallic markers and assessment of its accuracy.

A technique for simultaneous roentgen stereophotogrammetry (RS) was developed, and its accuracy was assessed. In vitro models fabricated from dried cadaveric C4 and C5 vertebrae were used to simulate the motion behavior of the cervical spine. Metallic markers made of Vitallium beads (diameter < 0.3 mm) were implanted into the posterior and anterior surfaces of each vertebra at surgically accessible locations to simulate the bead placement for both posterior and anterior surgical approaches to the cervical spine. A series of roentgen stereo pairs were obtained to systematically assess the accuracy (validity) of displacement measurements in anteroposterior (AP) translation, axial rotation, and flexion/extension. In addition, the effects of soft tissue density on the accuracy of the system were investigated by obtaining a series of roentgen stereo pairs with the experimental model immersed in a water bath. The coordinates of the metallic markers on the radiographs were then digitized by two raters who were not informed of the actual motion (i.e., blind study). The results indicated a high accuracy throughout the study. Overall root mean square errors were 0.07 mm for AP translation, 0.08 degrees for axial rotation, and 0.14 degrees for flexion/extension. The corresponding accuracy estimates (R2 values by linear regression analysis) were very high (0.992, 0.998, and 0.995) when the measurement results were compared with the actual displacements. The water bath did not affect measurement accuracy, indicating that soft tissue density should have little effect on the accuracy of the technique for in vivo applications. This system appears to be an accurate and reliable method for assessment of simulated in vivo cervical spine motion, regardless of the rater. The technique has been further used in in vivo assessment of cervical spine kinematics in one patient to confirm the efficacy of the developed technique.

Atlanto-Axial Joint↗

Nephrotoxicity from contrast material in renal insufficiency: ionic versus nonionic agents.

Controversy exists over whether use of low-osmolality contrast agents is of any benefit in mitigating the risk of contrast material-induced nephrotoxicity (CN) in patients with impaired renal function. To test this hypothesis, 101 adult inpatients with high serum creatinine levels (range, 1.4-2.4 mg/dL [120-210 mumol/L]) undergoing contrast material-enhanced computed tomography were randomized to receive ionic or nonionic (low-osmolality) contrast agents in a uniform dose. Changes in serum creatinine level at 48 hours were measured. Seven (14%) of the 50 patients receiving ionic contrast media experienced an increase of 25% or more in serum creatinine level. Only one (2%) of the 51 patients receiving nonionic contrast agents experienced such an increase, a statistically significant difference (P less than .05). In the subset of 25 diabetic patients, the difference was of a similar magnitude. These data suggest that ionic contrast media are more likely than nonionic contrast agents to cause mild exacerbation of renal insufficiency when given intravenously. However, there were no cases of clinically important CN in the study.

Adult↗

CT-guided percutaneous transpedicular biopsy of the spine.

Occasionally, vertebral body lesions are encountered that are ill suited to the standard posterolateral approach to biopsy. The authors used a transpedicular approach to spine biopsy in six such cases. The authors suggest that this approach be used when the location of the lesion does not allow easy access by means of the posterolateral approach.

Aged↗

Evaluation of effectiveness of a facet wiring technique: an in vitro biomechanical investigation.

The effects of facet wiring procedure commonly used for stabilizing cervical spines after laminectomy or bilateral facet dislocation on the motion behavior of whole cervical spines are investigated using a Selspot II system. A fresh human ligamentous intact specimen was potted at T1/T2 vertebra and clinically relevant loads applied to the topmost vertebra (C2) of the specimen. The resulting three rotational components of each of the five vertebral bodies (C3-C7) were recorded. Specimen was injured to mimic total laminectomies at C5 and C6 vertebral levels and tested again. The injured specimen was stabilized, using a facet wiring construct, across C4-C7 segment before testing for the final time. The injured specimens, compared to the intact specimens, demonstrated an increase in flexion-extension of about 10%. Facet wiring imparted stability to the cervical spine by stiffening segments up to roughly four times intact values.

Aged↗

Kinematics of the cervical spine: effects of multiple total laminectomy and facet wiring.

The effect of multiple-level total laminectomies followed by stabilization on the load-deformation behavior of the cervical spine is described. Fresh human ligamentous cervical spines (C2-T2) were potted and clinically relevant load types applied via a loading frame attached to the C-2 vertebra of the specimen. A set of three infrared light-emitting diodes (LEDs) were attached rigidly to each of five vertebrae (C3-7) to record their spatial locations after each load step application, using a Selspot II system. The specimen was tested again after total laminectomy performed on C5. The supraspinous, interspinous, and flavum ligaments between the C4-5 and C5-6 motion segments were cut; thereafter, the vertebral arch was removed. The specimen testing was resumed after inducing injury at C-6 in a similar fashion. The specimen was stabilized, using a facet wiring construct, across the C4-7 segment before testing for the final time. The load-deformation data of the injured and stabilized tests were normalized with regard to the corresponding results of the intact test. In flexion-extension mode, an increase in motion of about 10% after laminectomies was observed. Facet wiring was found to be an effective technique to stabilize injured cervical spines (approximately equal to 80% reduction in motion, compared with intact spines, was observed.

Biomechanical Phenomena↗