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Biomedical subjects

S D Cook

Publications and source records attributed to S D Cook.

At least 109 records · Page 6Linked to original sources

Individual specific bias usage of HLA-DR antigens in the restriction of myelin basic protein-reactive T cell clones.

Multiple sclerosis, a demyelinating disease of the human central nervous system occurs in genetically susceptible individuals through a presumably autoimmune mechanism directed against the myelin sheath. The influence of the major histocompatibility locus on T cell recognition of myelin basic protein (MBP), a suspected target autoantigen, was investigated by analyzing MBP-specific T cell clones generated from the peripheral blood of healthy individuals. Inhibition studies using monoclonal antibodies demonstrated that MBP recognition was restricted by HLA-DR antigens. MBP recognition of the majority of T cell clones from each individual was restricted predominantly by one of the DR alleles. Thus, there appears to be a bias in the use of allelic DR restricting elements for MBP responses.

Adult↗

Torsional resistance and wear of a modular sleeve-stem hip system.

The torsional resistance and wear debris generation of the modular sleeve and stem S-ROM total hip system was evaluated. The results indicate that slippage of the sleeve-stem interface may occur under physiological loading conditions. Slippage is more likely to occur if the junction is contaminated by blood or tissue, or if the stem is disengaged and reimplanted into the sleeve. Significant wear debris was generated during cyclic fatigue loading. The wear debris was of the size (less than 10 mum) readily ingested by macrophages. Particles of these dimensions have been associated with osteolysis, implant loosening and pain. Based upon the findings of this study the implantation of this type system must be carefully considered.

Corrosion↗

Bone ingrowth into a porous-coated total shoulder component retrieved postmortem.

An uncemented porous-coated humeral component, which functioned in vivo for over 2 1/2 years, was retrieved postmortem and examined histologically. Radiographs of the specimen revealed close approximation to the endosteal cortex medially and laterally. Apposition was limited or absent anteriorly and posteriorly. The overall extent of bone ingrowth was approximately 11% of the available pore volume with over 95% of ingrowth occurring in the medial and lateral quadrants. Bone ingrowth was limited anteriorly and posteriorly to regions in which spot welds were identified radiographically. There were no loose beads or coating failure observed.

Adult↗

No eye pad for corneal abrasion.

We have carried out a randomised clinical trial to assess the healing rate and level of discomfort experienced in two groups of patients with simple traumatic corneal abrasions. Patients treated with antibiotic ointment and mydriatic alone have a significantly improved healing rate compared with those treated with antibiotic ointment, mydriatic and a double eye pad with bandage (0.05 > p > 0.02). There was no significant difference in the level of discomfort experienced by the two groups.

Adolescent↗

A biomechanical comparison of intramedullary nailing systems for the humerus.

This study evaluated the rotational and bending stability of three interlocking nail systems in paired cadaveric humeri. The Russell-Taylor Humeral Interlocking Nail, the Seidel Humeral Locking Nail, and the True-Flex Humeral Nail were mechanically tested in torsion and four-point bending. The Russell-Taylor and the Seidel interlocking nails are reamed systems that rely on proximal interlocking screws and distal screws or phalanges respectively for rotational stability. However, axillary nerve damage may result during proximal screw placement, and these systems exhibit low resistance to rotation. The True-Flex intramedullary nail is an unreamed system that relies on cross-sectional geometry to achieve rotational stability. By not relying on interlocking screws for stability, nerve damage associated with the screw placement may be eliminated. However, the results indicate the cross-sectional geometry of the True-Flex nail is not able to provide the same degree of static locking as the Russell-Taylor or Seidel interlocking nails. Humeri implanted with the Russell-Taylor and Seidel nails also had a significantly greater torsional stiffness than the True-Flex nail. As expected, humeri implanted with the Russell-Taylor and Seidel nails also had a significantly greater bending stiffness than the True-Flex nail in both anterior-posterior and medial-lateral bending.

Absorptiometry, Photon↗

Comparison of patient and staff assessment of MS patients' health status.

This study compared change scores obtained on patient self-reported symptoms (MS-RS) with the neurological examination of the Kurtzke Functional Systems (FS) and change scores obtained on patient self-reported activities of daily living (ADL-MS) with the neurologist-determined Expanded Disability Status Scale (EDSS) that were obtained from two separate times separated by approximately seven months for 100 patients with multiple sclerosis. Percent agreement based on < or = 1 unit difference between patient and neurologists' change scores (Time 2-Time 1) ranged between 73% and 86% for MS-RS and FS measures and was 72% for ADL-MS and EDSS. Together, the ADL and MS-RS patient self-report scales provide health status information from the patient's perspective that can be useful in guiding the physical examination, in making comparisons from visit to visit and/or between visits, in assessing patients' quality of life, and in increasing patient satisfaction with medical care.

Activities of Daily Living↗

Complications related to modularity of total hip components.

We report complications from the use of modular components in 20 hip replacements in 18 patients. Fifteen complications (in 13 patients) were related to failure of a modular interface after operation. Femoral head detachment from its trunnion was seen in 6 hips from trauma (3), reduction of a dislocation (2), and normal activity (1). In one case the base of the trunnion fractured below an extra-long modular head. In seven other hips the modular polyethylene liner dislodged from its shell, causing severe damage to the shell in four cases with extensive metallosis. In one other hip an asymmetrical polyethylene liner rotated, resulting in impingement of the femoral component and recurrent dislocation. Operative errors were seen in five cases: implantation of a trial acetabular component in one; and mismatching between the size of the femoral head and the acetabular component in the others. Surgeons who use hip replacements with modular components should be aware of the potential for operative error and of the importance of early treatment for postoperative mechanical failure.

Adult↗

The effect of surface macrotexture on the mechanical and histologic characteristics of hydroxylapatite-coated dental implants.

The interface attachment strength and histology of HA-coated endosseous dental implants with surface texturing added to allow for mechanical interlocking of the implant to bone were evaluated in the canine mandibular model. Twenty-two adult mongrel dogs received eight implants (four per side) placed into healed extraction sites. Fifteen weeks post-implantation, the implants were evaluated mechanically by axial pull-out and torsional testing. Following testing, the specimens were evaluated quantitatively for histologic parameters of bone apposition, HA-coating thickness, and mode of interface failure. The addition of surface macrotexture (threads, grooves, and dimples) was not found to have a significant effect on axial pull-out strength compared with smooth implant controls. Similarly, mechanical testing in torsion failed to reveal any significant effect on implant-bone interface attachment due to surface macrotexture. Interface failure occurred primarily at the HA/substrate interface in all implant designs. Examination of HA-coating thickness revealed non-uniform coatings, particularly in the surface-textured designs. Although bone growth into the surface textures was observed in some cases, often only minimal or a thin osseous layer on the HA coating was observed. This factor most likely contributed to the lack of significant additional interface attachment strength in the textured designs. The reduction in areas of complete implant incorporation may also have exposed the HA coating to high interfacial loads and may be responsible for the greater HA coating break-up and presence of particles observed in the textured designs.

Animals↗

An in vivo analysis of an elliptical dental implant design.

The interface attachment strength and histology of an elliptical hydroxylapatite-coated (HA) endosseous dental implant were compared with those of an otherwise identical cylindrical dental implant. The implant designs were tested in two canine in vivo models: healed mandibular extraction sites and the femoral unicortical plug. The implants were evaluated 15 weeks post-implantation. The elliptical geometry of the dental implant was not found significantly to enhance axial pull-out strength or torsional implant-bone interface attachment in either in vivo model. The cylindrical implant absorbed more energy to failure in both the mandible and the femur; however, the difference was not statistically significant. Differences in the interface shear attachment strength between the two models (mandible and femur) were statistically significant when the maximum load to failure was normalized by the actual bone contact surface area. In all cases, femoral values were significantly greater. Examination of HA-coating thickness revealed uniform coatings on both implant types which were well maintained in vivo. Mechanical failure occurred primarily at the metal substrate-HA interface in each type of implant in both models. The amounts of bone apposition to both implants in both models were identical. Coating break-up and inflammatory response to the particulate debris were minimal.

Analysis of Variance↗

Antiviral agents for ocular adenovirus infections.

Despite significant knowledge of the molecular biology and genetics of adenovirus, no specific antiviral agent has been developed for use in adenovirus infections. This contrasts with the situation in herpes simplex virus (HSV) and human immunodeficiency virus (HIV) infections, in which antiviral agents target specific enzymes. Antiviral agents active against HSV and interferons have been used in the treatment of ocular adenovirus infections with limited effect. Some newer nucleoside analogues have inhibitory activity against adenovirus in vitro and their effect is being assessed in newly developed animal models. Live vaccines have been used in both the United States and Canada to protect military recruits against adenovirus-induced respiratory disease. However, the inoculating strains are not normally associated with epidemic keratoconjunctivitis (EKC). There is a low prevalence of antibody against strains of adenovirus inducing EKC. Until such time as specific antiviral agents against adenovirus are developed, the mainstays of therapy will remain topical antibiotics to eliminate any secondary bacterial infection and topical steroids to suppress the immune response against adenovirus or adenovirus-infected cells. Neither form of treatment is adenovirus specific.

Adenovirus Infections, Human↗

Posterior cruciate ligament avulsion in total knee arthroplasty.

An anatomic study was outlined to measure the strength of the posterior cruciate ligament after total knee arthroplasty. This interest was precipitated by a patient whose posterior cruciate ligament ruptured 6 months after a total knee arthroplasty. Six unembalmed knee specimens (three bilateral) were mounted in a mechanical tension-testing machine, and proximal tibial total-knee bone cuts were performed at successive 2 to 3 mm depths. At each level, the ligament was tested at physiologic tension. The posterior cruciate ligament failed at 7 to 10 mm of bone resected, with an average failure at 8.6 mm.

Aged↗

Elevated neopterin levels in Guillain-Barré syndrome. Further evidence of immune activation.

Neopterin is a by-product of guanosine triphosphate metabolism and is produced by macrophages in response to lymphocytic activation. We have studied serum neopterin levels in patients with Guillain-Barré syndrome to obtain further evidence of immune activation in this disease. Serum neopterin levels were significantly elevated in patients with Guillain-Barré syndrome compared with patients with other peripheral neuropathies and multiple sclerosis and with healthy control subjects. Serial analysis demonstrated that as neopterin levels fell, the clinical status of the patients with Guillain-Barré syndrome improved and soluble interleukin 2 receptor levels dropped. Thus, lymphocytic and macrophage activation may play a role in the pathogenesis of Guillain-Barré syndrome.

Adolescent↗

Hydroxylapatite coating of porous implants improves bone ingrowth and interface attachment strength.

The effect of a plasma-sprayed hydroxylapatite (HA) coating on the degree of bone ingrowth and interface shear attachment strength was investigated using a canine femoral transcortical implant model. Cylindrical implants were fabricated by sintering spherical Co-Cr-Mo particles 500-710 microns in diameter; the nominal implant dimensions were 5.95 +/- 0.05 mm diameter by 18 mm in length. One half of each implant was coated with hydroxylapatite, 25-30 microns in thickness, by a plasma-spray technique. Using strict aseptic technique, the implants were placed through both femoral cortices into defects approximately 0.05 mm undersized. After 2, 4, 6, 8, 12, 18, 26, and 52 weeks, the implants were harvested and subjected to mechanical pullout testing and undecalcified histologic evaluation. The application of the HA coating to porous implants enhanced both the amount of bone ingrowth and the interface attachment strength at all time periods. These differences were statistically significant for the percent of bone ingrowth at the 4-, 6-, 12-, 18-, 26-, and 52-week time periods, and interface shear strength values were significantly different at the 6-, 8-, 12-, 18-, and 26-week time periods. The rate of development of interface strength and bone ingrowth was also more rapid for the HA-coated implants. No evidence of any disruption, mechanical failure, or biologic resorption of the HA coating was observed. The results of the present study--demonstrating a beneficial effect of the HA coating at all time periods--are believed to be due to the use of paired comparisons, which allow assessment of subtle differences that might otherwise have been obscured by normal biological variability.

Analysis of Variance↗

Effects of Guillain-Barré sera containing antibodies against glycolipids in cultures of rat Schwann cells and sensory neurons.

Serum samples from 52 patients with the acute Guillain-Barré syndrome (GBS), 19 patients with other neurological disorders, and 18 healthy volunteers were tested for cytotoxicity in cultures of rat Schwann cells and dorsal root ganglion neurons. The samples were also examined by enzyme-linked immunosorbent assay for IgG and IgM antibodies against various acidic and neutral glycolipids. Samples from 16 of the 52 (31%) acute GBS patients and from 1 of the 6 patients with chronic inflammatory demyelinating polyneuropathy produced myelin breakdown in culture. Although 10 of the 16 cytotoxic acute GBS serum samples contained anti-glycolipid immunoglobulins, there was no correlation in individual samples between cytotoxic activity and the presence of antibodies against specific glycolipids. While our results do not exclude a role for anti-glycolipid antibodies in the pathogenesis of the acute GBS, the cytotoxic effects of acute GBS serum in cultures of Schwann cells and sensory neurons are probably not due to these antibodies alone.

Animals↗

Antibodies to acidic glycolipids in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy.

Using an enzyme-linked immunosorbent assay and a thin-layer chromatography-immunostaining procedure, we detected serum antibodies against acidic glycolipids in 36 of 53 patients with Guillain-Barré syndrome (GBS) and 8 of 16 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Although we also found anti-acidic glycolipid antibodies in 4 of 13 patients with other neurological diseases; 2 of 10 patients with multiple sclerosis; 8 of 33 patients with inflammatory, infectious, allergic or autoimmune disorders and 3 of 32 healthy subjects, the levels of antibodies in these controls were much lower than in GBS patients. There were several patterns of reactivity of GBS sera including antibodies to LM1 and HexLM1, GM1 or GD1b or both, various other gangliosides, sulfated glycolipids, and as yet unidentified glycolipids. Sera from 30% of GBS patients had antibodies against two or more antigenically distinct acidic glycolipid antigens. Levels of anti-acidic glycolipid antibodies correlated with clinical symptoms in 9 of 11 GBS patients. While the increased incidence of antibodies to acidic glycolipids in patients with GBS (P less than 0.001) and CIDP (P less than 0.025) compared to controls could be an epiphenomenon, anti-acidic glycolipid antibodies may play a role in nerve injury in some GBS and CIDP patients.

Carbohydrate Sequence↗

Anti-GM1 IgA antibodies in Guillain-Barré syndrome.

Serum anti-GM1 IgA antibodies were detected in 15 of 53 (28%) patients with the acute Guillain-Barré syndrome (GBS) and in one of 26 (4%) patients with other neurological diseases. Although nine GBS patients had anti-GM1 IgA titers of 1:200 or less, six patients had titers of 1:800 or more. Some GBS patients with anti-GM1 IgA antibodies also had antibodies against GD1b or GM2 or both. The presence of markedly elevated anti-GM1 IgA was associated with a poor clinical outcome at 6 and 12 months following onset of the GBS. The possible pathogenetic role of anti-GM1 IgA antibodies remains to be established.

Antibodies↗

Anti-MAG IgM paraproteins from some patients with polyneuropathy associated with IgM paraproteinemia also react with sulfatide.

Sera from five of 11 patients with neuropathy associated with IgM paraproteinemia (NAIgMPP) and reactivity against myelin-associated glycoprotein (MAG) also had elevated levels of IgM against sulfatide. Although three patients had anti-sulfatide IgM titers of less than or equal to 1:1000, two patients had titers of greater than or equal to 1:50,000. Absorption of patient serum with sulfatide revealed that anti-MAG IgM paraproteins in two patients with high titer anti-sulfatide IgM crossreacted with sulfatide. Our study is the first to show that some anti-MAG IgM paraproteins crossreact with sulfatide, a major acidic glycolipid of myelin. Moreover, some patients with NAIgMPP have polyclonal anti-sulfatide IgM in addition to anti-MAG IgM paraproteins. Therefore, sulfatide may be a target antigen in some patients with NAIgMPP.

Antibodies↗