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Biomedical subjects

S D Cook

Publications and source records attributed to S D Cook.

At least 73 records · Page 4Linked to original sources

Acanthamoeba keratitis: risk factors and outcome.

AIMS/BACKGROUND: This study was initiated to investigate risk factors for and outcome of Acanthamoeba keratitis. METHODS: Results of treatment were studied in 22 patients (23 eyes) presenting to Bristol Eye Hospital between 1985 and February 1995. Details related to the use and disinfection of contact lenses were also obtained. An additional two patients who were seen at Bristol but mainly treated elsewhere were surveyed for contact lens related information only. RESULTS: The incidence of Acanthamoeba keratitis rose substantially in the 1990s: three patients presented before 1990, while the remaining 21 presented between January 1990 and February 1995. Eleven patients have presented since january 1994. All of the patients in this series were contact lens wearers, 16 (67%) using daily wear disposable contact lenses. Contact lens disinfection data were available in 22 patients of whom 11 (50%) were using chlorine disinfectant. Other types of disinfection were much less common. Four patients (18%) had not used any disinfectant. During the course of the series the average diagnostic delay has fallen markedly, although in 77% of patients a diagnosis of a viral keratitis, most commonly herpes simplex, was made on first presentation. All but three of the series were treated with a combination of polyhexamethylene biguanide and propamidine isethionate. Penetrating keratoplasty was performed in 9/23 eyes (39%); in all of these eyes diagnosis was delayed for at least 6 weeks. All but one of the eyes in the series achieved a visual acuity of 6/9 or better after treatment, and 18 eyes (78%) saw 6/6 or better. CONCLUSIONS: Most patients with Acanthamoeba keratitis can now expect a good visual result and cure by medical therapy alone is favoured by early diagnosis.

Acanthamoeba Keratitis↗

Canine distemper virus-specific antibodies in multiple sclerosis.

Current postulates support the idea that MS is triggered by an infectious agent or agents through an autoimmune reaction directed against brain antigens in genetically susceptible individuals. Evidence for an infectious etiology of MS is indirect. We have proposed that MS may, in some instances, be due to a zoonotic infection and that canine distemper virus, a measles-like virus in dogs, is a likely candidate in the causation of this disorder. The high homology between canine distemper and measles virus proteins has made it extremely difficult to distinguish distemper from measles antibodies serologically. We now provide evidence that humans can be infected with this neurotropic dog virus. Furthermore, a high titer of canine distemper virus antibodies is significantly associated with MS. Identification of the etiologic agent in MS may lead to the elucidation of disease pathogenesis and to disease prevention through appropriate public health and vaccination programs.

Adolescent↗

The effect of operative fit and hydroxyapatite coating on the mechanical and biological response to porous implants.

UNLABELLED: Femoral intramedullary implants were constructed by threading 4.0-millimeter-thick disks with a titanium-alloy (Ti-6Al-4V) porous bead coating onto a two-millimeter-diameter threaded rod. Each porous-coated disk, which was 6.0, 8.0, 9.0, or 10.0 millimeters in diameter, was separated by a two-millimeter-thick acrylic disk with a diameter of ten millimeters. Implants with and without a hydroxyapatite coating of twenty-five micrometers were inserted into fifteen skeletally mature adult mongrel dogs. The femoral canal was sequentially reamed bilaterally to a ten-millimeter diameter, resulting in uniform initial implant-bone interface gaps of 0.0, 0.5, 1.0, and 2.0 millimeters. Each animal received paired hydroxyapatite-coated and uncoated implants. Three animals each were killed at four, eight, twelve, twenty-four, and fifty-two weeks after the implantation. The harvested femora were sectioned through the acrylic spacers, transverse to the long axis, to produce individual push-out test specimens for mechanical testing. Characteristics of interface attachment were determined with test fixtures that supported the surrounding bone to within 150 micrometers of the interface. Histological sections were prepared, and the amount of bone within the porous structure and the amount of the original gap that was filled with new bone were quantified with a computerized video image-analysis system. Mechanical attachment strength and bone ingrowth were found to increase with the time after implantation and with a decrease in the size of the gap. Placement of the implant in proximal (cancellous) compared with distal (cortical) locations had no significant effect on the strength of attachment, bone ingrowth, or gap-filling. However, implants with a large initial gap (1.0 or 2.0 millimeters) demonstrated greater attachment strength in cancellous bone than in cortical bone. With a few exceptions, hydroxyapatite-coated implants with an initial gap of 1.0 millimeter or less demonstrated significantly increased mechanical attachment strength and bone ingrowth at all time-periods. Interface attachment strengths were positively correlated with bone ingrowth, the time after implantation, the use of a hydroxyapatite coating, and decreasing initial gap size. CLINICAL RELEVANCE: Initial implant-bone apposition is thought to be a prerequisite for good biological fixation. This apposition is often not achieved because of the design of the implant or instruments and the operative technique. Poor initial fit during the operation may decrease the longevity of the implant. The results of the present study indicate that attachment strength and bone ingrowth are significantly affected by gaps in the interface, particularly those of more than 1.0 millimeter.(ABSTRACT TRUNCATED AT 400 WORDS)

Alloys↗

The effect of warfarin on the attachment of bone to hydroxyapatite-coated and uncoated porous implants.

The attachment of bone to hydroxyapatite-coated and uncoated porous implants made of cobalt-chromium-molybdenum alloy was investigated with and without postoperative administration of warfarin sodium. The implants were placed transcortically in the femoral diaphysis of adult female goats and were evaluated after three, six, and twelve weeks in situ. Mechanical push-out testing and histological evaluation revealed that the attachment strength and the ingrowth of bone at the bone-implant interface increased with time in situ for both the hydroxyapatite-coated and the uncoated implants. The administration of warfarin significantly impaired both the attachment strength and the ingrowth of bone at twelve weeks. At twelve weeks, the attachment strength and bone ingrowth of the hydroxyapatite-coated implants in the animals that had received warfarin were statistically equal to those of the uncoated implants in the control animals.

Analysis of Variance↗

Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates.

The effect of recombinant human osteogenic protein-1 on the healing of segmental bone defects was studied in twenty-eight African green monkeys (Cercopithecus aethiops). A 2.0-centimeter osteoperiosteal defect was created in the middle of the ulnar shaft in fourteen animals and in the diaphysis of the tibia in the other fourteen. The ulnar defect was filled with an implant consisting of 1000 micrograms of recombinant human osteogenic protein-1 in 400 milligrams of bovine bone-collagen carrier in six animals, with collagen carrier alone in two animals, and with autogenous cancellous bone graft from the contralateral tibia and femur in six animals. The tibial defect was filled with 250, 500 (two tibiae), 1000, or 2000 micrograms of recombinant human osteogenic protein-1 in 400 milligrams of collagen carrier in five animals, with collagen carrier alone in one animal, and with autogenous cancellous bone graft in six animals; in the two remaining animals (controls), the tibial defect was left unfilled. The tibial defects were stabilized with an intramedullary Steinmann pin. All animals were killed at twenty weeks postoperatively. Healing of the defects was evaluated with biweekly radiographs, with histological examination, and with mechanical testing. Radiographically, all of the defects that had been treated with recombinant human osteogenic protein-1 exhibited new-bone formation, but they differed in the degree of healing and remodeling. Five of the six ulnae treated with recombinant human osteogenic protein-1 and four of the five tibiae treated with this substance exhibited complete healing at six to eight weeks, with bridging of the defect by new bone first observed at four weeks. The two unhealed defects both exhibited new-bone formation but incomplete union, which precluded mechanical testing. No defect that had been filled with collagen carrier or that had been left unfilled exhibited any signs of healing or major new-bone formation. None of the six ulnae that had been filled with autogenous bone graft exhibited complete healing, compared with five of the six tibiae that had been so treated. Histological evaluation of the defects treated with recombinant human osteogenic protein-1 revealed the formation of new cortices with areas of woven and lamellar bone and normal-appearing marrow elements at twenty weeks postoperatively. The tibial defects that had been treated with autogenous bone graft had a similar appearance. All control ulnar and tibial defects and all ulnar defects that had been treated with autogenous bone graft had fibrous union with little new-bone formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Posterior fracture-dislocation of the hip in a jogger.

Posterior fracture-dislocation of the hip is an uncommon athletic injury, occasionally seen in contact and high-energy sports. The mechanism of injury in this case highlights the high hip joint forces possible during running. The key treatment principle is early reduction of the hip joint, since the incidence of osteonecrosis of the femoral head and degenerative arthrosis increases with delay. Operative treatment will frequently be required to achieve a stable, congruent reduction of articular surfaces, essential for good long-term results. Partial weight-bearing exercise such as swimming and bicycling may aid rehabilitation. Long-term follow-up, with serial radiographs, is important to detect late complications.

Acetabulum↗

Adjunct fibula strut bone graft in resurfacing hip arthroplasty.

Femoral neck fracture following surface replacement is a reported complication. Adjunct autogenous fibula strut bone grafting has been proposed as a means of reducing or eliminating this occurrence. This paper reports the long-term follow-up of two cases. One patient did well for 9 years prior to sustaining a traumatic femoral neck fracture while intoxicated; the second patient continues to do well 8.5 years postoperatively. While definite conclusions cannot be drawn, these two patients represent our longest-clinical successes using surface replacement arthroplasty.

Adult↗

Preliminary evaluation of titanium-coated PEEK dental implants.

A total of 40 titanium-coated and uncoated polyetheretherketone (PEEK) cylindrical implants was placed in unicortical sites in the femurs of four mongrel dogs. The implants were evaluated mechanically and histologically at periods of four and eight weeks. Interface attachment strength was determined for each specimen, as were measurements of bone contact, porosity, bone ingrowth, inflammatory response, and mode of failure. Statistical analysis revealed that the uncoated implants had a significantly higher interface shear strength at four weeks, but that there was no significant difference from the coated implants at eight weeks. At both four and eight weeks, the titanium-coated specimens had significantly higher percentages of bone contact. There was no significant increase in bone contact between four and eight weeks for either the coated or uncoated specimens.

Analysis of Variance↗

In vivo evaluation of CSTi dental implants in the presence of ligature-induced peri-implantitis.

The histology of a CSTi (cancellous-structured titanium) porous-coated cylindrical dental implant was compared with that of a solid control HA (hydroxylapatite)-coated dental implant with the same geometry. A particular concern with the use of porous-coated implants in dental applications is the possibility of infection due to direct exposure to the outside environment. Three implants of each type were placed in healed mandibular sites of 14 canines, and after eight weeks of healing, an abutment was placed on each implant. In one half of the implants, ligature-induced peri-implantitis was introduced. The implants were evaluated at four, eight, 16, and 26 weeks post-ligature placement. Bone ingrowth percentages were relatively high for both ligated and non-ligated CSTi specimens, with mean values ranging from 59% to 71%. There was no significant difference in bone ingrowth percentages between ligated and non-ligated specimens at any of the evaluation periods. For the HA-coated specimens, there was also no significant difference in bone contact percentages between ligated and non-ligated implants. There was not a significant decrease in bone contact of bone ingrowth with time for either the ligated or non-ligated implants. No loss of bone along the porous coating or coating-bone interface was observed due to the peri-implantitis, although HA failure was seen primarily in ligated specimens. When crestal bone loss was evaluated on histologic sections and radiographs, it was found that there was no significant difference in loss between CSTi- and HA-coated implants at all time periods for ligated and non-ligated specimens. Histological inspection of the CSTi implants did not reveal any migration of infection or inflammation through the porous coating resulting in bone ingrowth loss.

Alveolar Bone Loss↗

In vivo evaluation of a CSTi dental implant: a healing time course study.

The in vivo interface attachment strength and histology of CSTi (cancellous-structured titanium)-coated cylindrical dental implants were compared with those of solid HA-coated dental implants of the same dimensions and geometry. The implants were placed in healed extraction sites in the mandibles and prepared unicortical sites in the femurs of canines. The mandibular implants were evaluated at two, four, eight, and 12 weeks post-implantation, and the femoral implants were evaluated at two, four, eight, 12, 16, 24, and 34 weeks post-implantation. The interface attachment strength of the CSTi implants placed in the mandible at two, four, eight, and 12 weeks was not significantly different from that of the control HA-coated implants. In the femurs, the CSTi implants were significantly stronger than the HA-coated implants at all time periods except 12 weeks (two, four, eight, 16, 24, and 34 weeks). The CSTi implants were able to achieve high percentages of bone ingrowth in the mandible and femur of up to 92% at the later time periods, thus providing a sound interface bond.

Analysis of Variance↗

Evaluation of recombinant human osteogenic protein-1 (rhOP-1) placed with dental implants in fresh extraction sites.

This study used the canine mandibular model to evaluate the efficacy of recombinant human osteogenic protein-1 (rhOP-1) for accelerating the healing of fresh dental extraction defects and in encouraging osseointegration of dental implants. Eight implants, four hydroxylapatite (HA)-coated and four non-coated, were placed in each mandible of four adult male mongrel dogs immediately after extraction of the eight premolars. The rhOP-1 was placed in all extraction sites with and without implants on the left side of the mandible. All animals were killed at 12 weeks postoperatively; histologic analysis was performed, including measurement of the new bone formation within the extraction defects, implant incorporation, and implant-bone interface characteristics, including percent bone and fibrous tissue apposition. Extraction sites treated with rhOP-1 were completely filled with new bone and were well incorporated with the host bone at 12 weeks post-operative. New bone had filled the untreated defect sites; however, the amount, density, and degree of remodeling were less than was observed in rhOP-1 sites. Small increases in osseointegration and adjacent new bone formation were apparent surrounding implants placed with rhOP-1. However, good initial implant fit and the small amount of rhOP-1 delivered to the site in this model may have mitigated any large differences. The results of this study demonstrate that new bone formation can be induced around and adjacent to a dental implant placed in a fresh extraction site with a recombinantly produced bone inductive protein.

Alveolar Process↗

Effects of bone mineral density on pedicle screw fixation.

STUDY DESIGN: In an attempt to evaluate the effects of bone mineral density on the quality of fixation of pedicle screws in the lumbar spine, the axial pullout force was determined and compared in normal and osteoporotic human lumbar spines. OBJECTIVES: Four techniques of screw hole preparation were evaluated. Two pedicle screw/offset laminar hook constructs also were evaluated to determine whether the adjunct fixation of the laminar hooks would improve quality of fixation to a level sufficient to allow their use in the osteoporotic lumbar spine. METHODS: Pedicle screws were inserted by one of the listed techniques into fresh frozen cadaveric human spines. The fixation strength then was evaluated by pullout on a uniaxial testing frame. RESULTS: Bone mineral density was a strong influence on axial pullout force. In normal bone, the method of screw hole preparation did not significantly affect the quality of fixation. However, in the osteoporotic spine, either an untapped screw hole or the tapping of a screw hole with a 5.5 mm tap improved the pullout force a statistically significant amount (P < 0.003). Also, a pedicle screw with offset hooks at two adjacent levels improved the fixation significantly, increasing the pullout force to twice the expected value. CONCLUSION: Pedicle screw pullout strength was highly correlated with bone mineral density. A 5.5 mm tap or preparation with a ganglion knife improved pullout strength. Use of pedicle screws in conjunction with laminar hooks at two levels improved pullout strength.

Biomechanical Phenomena↗

Reduction in perineural scar formation after laminectomy with Polyactive membrane sheets.

STUDY DESIGN: The effectiveness of Polyactive (Osteotech, Inc., Shrewsbury, NJ), an elastomeric segmental copolymer, as a barrier material for the prevention of perineural scar formation was evaluated in eight adult mongrel dogs. Two animals each were killed at 2, 4, 8, and 12 weeks postoperation. OBJECTIVE: This study determined the ability of a Polyactive membrane to prevent perineural scar and compared the results to those obtained using free fat graft and nonimplanted control subjects. SUMMARY OF BACKGROUND DATA: Perineural scar formation after laminectomy presents considerable morbidity in lumbar surgery. To date, a wide variety of materials has been evaluated to prevent scar formation including free fat grafts, mechanical barrier devices, hemostatic agents, and anti-inflammatory drugs. However, all studies indicate scar formation is present, and the search for an effective barrier continues. METHODS: Gross dissection, radiographic studies, including computed tomography and magnetic resonance imaging, and histologic sections were used to evaluate the presence and degree of perineural scarring. If scarring was evident in each of the evaluations, the degree was graded on a 0-3 scale where: 0 = no scarring; 1 = mild scarring; 2 = moderate scarring; and 3 = extensive scar formation. RESULTS: Polyactive membranes were an effective barrier with only minimal scar formation to the dura observed at any time period. Free fat graft was an effective barrier to scar formation at early time periods; however, progressive fat graft degradation with some increased scarring was observed at latter time periods. Nonimplanted control defect sites resulted in moderate to severe scar formation to the dura as early as 2 weeks postimplantation. CONCLUSIONS: The results indicate Polyactive is a reliable and effective means of reducing perineural scar formation. The effectiveness of the Polyactive membrane could be improved markedly if techniques or methods to ensure retention of the membrane in the proper position were developed.

Adipose Tissue↗

In vivo evaluation of anterior cervical fusions with hydroxylapatite graft material.

STUDY DESIGN: The efficacy of solid hydroxylapatite (HA) blocks for obtaining cervical interbody fusion was studied in a canine model. Each of 21 adult colony-reared hounds received a hydroxylapatite implant and an autogenous bone graft in the C3-C4 and C5-C6 disc interspaces. Seven dogs each were killed at 6, 12, and 26 weeks postoperation. OBJECTIVE: This study determined the rate, mechanical strength, and histologic characteristics of cervical interbody fusions achieved using a hydroxylapatite (HA) block and compared the results to those obtained with autogenous iliac crest bone graft. SUMMARY OF BACKGROUND DATA: The use of corticocancellous autograft has been successful in a high percentage of anterior cervical interbody fusions. Calcium phosphate ceramics may provide an alternative to autogenous and allogenous tissue. These materials are biocompatible and capable of direct intimate bonding with bone because of their chemical similarity to bone mineral. METHODS: Radiographic evaluation including plain radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) studies were used to determine fusion quality. Specimens were also subjected to mechanical testing to determine bending and torsional stiffness as well as ultimate load to failure. Histologic evaluation included integrity and incorporation of the graft materials and interface characterization. RESULTS: The CT images were well correlated with plain radiographs and demonstrated progressive incorporation of the graft materials with time. Magnetic resonance images were of little value in evaluating quality of fusion; the autograft sites demonstrated progressive disc height loss with time. Minimal disc height loss was observed with HA blocks. There was no statistical difference in torsional stiffness for the HA blocks and autogenous bone grafts at any time period. In bending, the HA block sites were significantly stiffer at 6 weeks (P < 0.005). There was no statistical difference in the ultimate failure load for the HA and autogenous bone grafts. Histologically, the HA blocks demonstrated areas of direct bone apposition with increased bone appositions and implant incorporation with time. At 6 and 12 weeks postoperation, the autograft sites demonstrated areas of graft resorption and some new bone formations. By 26 weeks, new bone was continuous with the vertebral endplates. CONCLUSIONS: The results indicate that HA blocks may provide an alternative to autogenous graft materials for anterior cervical interbody fusion. Block slippage and/or fracture may occur in a small number of patients but is primarily related to insertion technique and does not appear to significantly alter the final result.

Animals↗

In vivo evaluation of recombinant human osteogenic protein (rhOP-1) implants as a bone graft substitute for spinal fusions.

STUDY DESIGN: Posterior spinal fusion segments were evaluated in adult mongrel dogs at 6, 12, and 26 weeks post-implantation. Four sites on each animal received implants consisting of recombinant human osteogenic protein-1 on a bone collagen carrier, bone collagen carrier alone, autogenous iliac crest bone, or no implant material. OBJECTIVE: To determine the efficacy of recombinant human osteogenic protein-1 as a bone graft substitute in achieving posterior spinal fusion and compare the results to those obtained using autogenous bone graft. SUMMARY OF BACKGROUND DATA: Posterior spinal fusion generally includes onlay grafting of autogenous or allogeneic bone after decortication of bony surfaces of the vertebral elements. The search for an acceptable bone graft substitute material has in recent years centered upon proteins capable of inducing bone in vivo. Recombinant human osteogenic protein-1 has demonstrated efficacy in healing large segmental osteoperiosteal defects in rabbits, dogs, and monkeys and appears ideally suited as a bone graft substitute for spinal fusions. METHODS: The quality of fusion and new bone formation was evaluated using plain films, computed tomography, and magnetic resonance imaging. RESULTS: Radiographic and histologic studies demonstrated that recombinant human osteogenic protein-1-treated fusion segments attained a stable fusion by 6 weeks post-implantation and were completely fused by 12 weeks. The autograft sites demonstrated fusion at 26 weeks post-implantation. CONCLUSIONS: The results indicated that recombinant human osteogenic protein-1 is an effective bone graft substitute for achieving stable posterior spinal fusions in a significantly more rapid fashion than can be achieved with autogenous bone graft.

Animals↗

Induction of autologous mixed lymphocyte culture responses by myelin basic protein-reactive T cell clones.

Myelin basic protein is an autoantigen present in the central nervous system suspected to be the target of destruction in multiple sclerosis. In the present study, we have demonstrated that T cell clones specific for myelin basic protein have the ability to induce proliferative responses in resting T lymphocytes in the autologous mixed lymphocyte culture (AMLC). T cell recognition of the AMLC stimulatory determinants on the clones required the presence of autologous monocytes. T lymphocytes primed against an autologous myelin basic protein-specific T cell clone displayed specific memory responses against the original stimulating clone and failed to exhibit secondary reactivity to 'sister' myelin basic protein-reactive clones and to autologous T cell clones specific for another antigen. Monoclonal antibodies specific for class II HLA-DR antigens inhibited secondary AMLC responses. Modulation of the T cell receptor from the surface of the clones decreased their AMLC stimulatory ability. These results indicate that idiotype-like determinants on the T cell receptor of autoantigen-specific T cell clones are capable of triggering anti-idiotypic T cell responses.

Cells, Cultured↗

Triple-dose versus single-dose gadoteridol in multiple sclerosis patients.

Nine patients with multiple sclerosis underwent brain magnetic resonance imaging (MRI) to evaluate the contrast enhancement of individual lesions after a single dose and a triple dose of gadolinium. A single dose (0.1 mmol/kg) of gadoteridol was administered and after a delay, axial T1-weighted images were obtained. After an additional 0.2-mmol/kg dose, the same T1-weighted sequence was repeated. An unblinded reader simultaneously viewed the images from both doses, and utilizing a computer console to rule out flow artifacts, created a gold standard of "definite" enhancing lesions. Using this system, he determined that there was a total of 12 definite enhancing lesions among the patients. This reader also evaluated lesion conspicuity. The contrast-noise ratio was calculated for each lesion. A second reader, blinded to the dose used, then evaluated the number of enhancing lesions at both doses. The unblinded reader noted increased lesions at both doses. The unblinded reader noted increased lesion conspicuity after the triple dose. Contrast-noise ratios were significantly (p < 0.001) higher after the triple dose (mean, 9.19) than after the single dose (mean, 2.97). The blinded reader detected 11 of the 12 definite lesions on MRIs after the triple dose (sensitivity, 92%) but saw only 6 on MRIs after the single dose (sensitivity, 50%). The difference was significant (p < 0.001). Subjective analysis of the films revealed an increase in "ghosting artifacts" at the high dose. Administration of triple-dose gadolinium provides increased lesion conspicuity and an improved lesion detection rate when compared to single-dose gadolinium in patients with multiple sclerosis.

Brain↗