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Biomedical subjects

D P McGowan

Publications and source records attributed to D P McGowan.

6 recordsLinked to original sources

Amyloid-like inclusions in Huntington's disease.

Huntington's disease is a progressive, autosomal dominantly inherited, neurodegenerative disease that is characterized by involuntary movements (chorea), cognitive decline and psychiatric manifestations. This is one of a number of late-onset neurodegenerative disorders caused by expanded glutamine repeats, with a likely similar biochemical basis. Immunohistochemical studies on Huntington's disease tissue, using antibodies raised to the N-terminal region of huntingtin (adjacent to the repeat) and ubiquitin, have recently identified neuronal inclusions within densely stained neuronal nuclei, peri-nuclear and within dystrophic neuritic processes. However, the functional significance of inclusions is unknown. It has been suggested that the disease-causing mechanism in Huntington's disease (and the other polyglutamine disorders) is the ability of polyglutamine to undergo a conformational change that can lead to the formation of very stable anti-parallel beta-sheets; more specifically, amyloid structures. We examined, using Congo Red staining and both polarizing and confocal microscopy, post mortem human brain tissue from five Huntington's disease cases, two Alzheimer's disease cases and two normal controls. Brains from five transgenic mice (R6/2)(12) expressing exon 1 of the human huntingtin gene with expanded polyglutamine, and five littermate controls, were also examined by the same techniques. We have shown that some inclusions in Huntington's disease brain tissue possess an amyloid-like structure, suggesting parallels with other amyloid-associated diseases such as Alzheimer's and prion diseases.

Alzheimer Disease↗

Bone registration method for robot assisted surgery: pedicle screw insertion.

A registration method that identifies bone geometry with respect to a robotic manipulator arm is presented. Although the method is generally applicable to many orthopaedic internal fixation procedures, it was only demonstrated for the insertion of pedicle screws in vertebral bodies for spine fixation. The method relies upon obtaining an impression of the vertebral bodies. Computerized tomography (CT) scans of both vertebrae and mould are reconstructed using a computer aided engineering (CAE) system. From the reconstructions, the surgeon is able to do preoperative planning including selection of pedicle screw diameter, direction of screw through pedicle, point of entry and length of engagement. The three-dimensional models are than meshed to determine positions of the surgeon's preoperative plan relative to the mould. Intra-operative positions are defined in space by a mechanical fixture rigidly attached to the mould and designed to allow a manipulator end-effector to recognize the global coordinates of the in vivo spine. The theory and methodology were validated using a five-axis manipulator arm. This initial presentation assumes and allows no relative motion between vertebrae in vivo.

Bone Screws↗

Touch sensitivity of the eyelid margin and palpebral conjunctiva.

Using a slit-lamp biomicroscope mounted Cochet-Bonnet aesthesiometer, the touch sensitivity of the eyelid margin and palpebral conjunctiva was determined for both upper and lower lids in 30 subjects. Thresholds for the occlusal surface of the lid, the marginal angle and the middle of the tarsus were measured centrally. A significantly higher touch sensitivity was found for the marginal zone compared with the occlusal surface, and tarsal conjunctival sensitivity was substantially the lowest. The occlusal and marginal zones of the lower lid displayed a significantly higher touch sensitivity than the upper lid but the tarsal sensitivity of the two lids was similar. The sharp peaking of sensitivity at the leading edge of each eyelid provides a mechanism for the detection of superficial foreign bodies and presumably augments the protective role of the cornea. A large inter-subject variation in marginal touch sensitivity was found which may explain individual variation in contact lens adaptation.

Adolescent↗

Strength reductions from trabecular destruction within thoracic vertebrae.

An in vitro model of metastatic lesions in thoracic vertebrae was used to determine if the reduction in vertebral cross-sectional area could be used to predict the associated strength reduction. Defects, entirely within the trabecular bone, were created in alternating vertebrae of unembalmed human thoracic spines. The adjacent vertebrae were tested intact and served as controls. Defect size was determined as the cross-sectional area of the defect divided by the nominal cross-sectional area of the vertebral body midplane. Vertebrae were tested to failure using combined axial-flexion loads. For each spine, a linear regression was determined between the cross sectional area of the superior endplate and the load at failure for the intact vertebrae. The intact strength of bodies with defects was estimated from this regression. The normalized strength of thoracic vertebrae with trabecular defects was linearly related to the reduction in cross-sectional area (normalized failure load = 1.0-Ad/Ai, r2 = 0.51; Ad = cross-sectional area of defect; and Ai = intact cross-sectional area at midplane). The data suggest that the strength reduction due to lytic defects within the centrum of thoracic vertebrae is proportional to the cross-sectional area of bone resorbed.

Aged↗

A biomechanical investigation of short segment spinal fixation for burst fractures with varying degrees of posterior disruption.

A biomechanical study was performed to evaluate the effectiveness of the Fixateur Interne pedicle screw system and the Syracuse I-Plate anterior fixation system. A total of 12 fresh frozen cadaver spines were tested intact, after burst fracture was created and application of a fixation device (six each), and after six serial transections of posterior ligaments and bony structures. Spines were loaded to a maximum of 10 N-m in flexion, extension, left and right lateral bending, and clockwise and counter-clockwise rotation. Results indicate that both systems reduce spinal flexibility in flexion, extension, and lateral bend loading when used to reduce and fix a classic burst fracture without posterior disruption. No decrease in flexibility was found in axial rotation for either device. After transection of all posterior elements, the I-Plate construct became much more flexible than the intact spine in flexion, extension, and axial rotation loading. The internal fixator construct retained more stability than the I-Plate construct after transection of posterior elements in flexion and extension loading, but was considerably more flexible than the intact spine in axial rotation loading. The results imply that the posterior internal fixator provides much better stabilization than the anterior I-Plate for those cases in which there is a large amount of posterior disruption in addition to an anterior burst injury. Neither device provides extensive support in axial rotation loading.

Aged↗