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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
PubMed1995

Multiple sclerosis: immune mechanism and update on current therapies.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) afflicting approximately 250,000 individuals in the United States. This inflammatory disease has variable clinical manifestations, ranging from a relapsing-remitting course to a chronic progressive disease. Approximately one third of MS patients have chronic progressive disease often leading to severe impairment of mobility, paralysis, poor vision, and disturbances of bladder and bowel function. Although the etiology and pathogenesis remain unknown, accumulating evidence supports the hypothesis that exposure to an as-yet-unidentified infectious agent(s) triggers an aberrant immune response against self nervous tissue in genetically susceptible individuals. The tenfold higher concordance rate for MS in monozygotic twins compared to dizygotic twins, the increased incidence of MS in women compared to men (2:1), and the familial and racial occurrence of MS provide strong evidence that genetic factors influence susceptibility to MS. The major predisposing genes in MS are the human leukocyte antigen (HLA) class II molecules, DR15 and DQw6, molecularly defined as HLA-DRB1, 1501-DQA1 0102-DQB1 0602. In certain ethnic groups, MS susceptibility is more strongly associated with other DR molecules. Environmental factors are also believed to play a role, as suggested by the unique worldwide prevalence, migration effects, and epidemiological studies. Increased serum and cerebrospinal fluid antibody titers to numerous viruses have been reported; however, there have been no confirmed studies detecting viral RNA or antigen in MS brain tissue. At the present time, no known treatment can significantly alter the progression of MS. Based on the postulate that MS is an autoimmune disease associated with abnormalities in immunoregulation, a number of different immunosuppressive and immunomodulating agents have been tested as therapeutic modalities. In this article, we review the circumstantial evidence suggesting that immune system abnormalities are associated with the disease process, and provide an update on current therapies used in MS.

Animals↗
PubMed1995

Influence of implant location on the mechanical characteristics using the transcortical model.

Mechanical evaluation of implants harvested following surgical implantation is often performed as part of the screening process for new materials or surface textures. The question of randomization with respect to implant placement often arises when attempting to design a study to evaluate several implant types, while minimizing the number of animals required to perform the investigation. The purpose of this study was to analyze the effects of implant placement within the canine femur on mechanical characteristics of the bone-implant interface when using the transcortical model. Both smooth and porous-surfaced implants were evaluated at several time periods to determine the effects of placement in the medial versus left cortex, proximal versus distal placement, and left versus right femur. The smooth-surfaced implants demonstrated a significant effect due to proximal versus distal placement within the femur only. There were no other significant comparisons. Porous-surfaced implants demonstrated no significant effects due to placement within the femur. The results demonstrate the necessity for careful study design when evaluating smooth surfaced implants; however, paired comparisons in either the medial versus lateral cortex or left versus right femur will provide unbiased comparisons between the implants.

Alloys↗
PubMed1995

In vivo mechanical and histological characteristics of HA-coated implants vary with coating vendor.

The purpose of this study was to evaluate the interface attachment strength and histology of hydroxylapatite (HA) coated and uncoated titanium and cobalt-chromium alloy implants. The canine transcortical plug model was utilized. Four different hydroxylapatite coatings were evaluated. In vitro analysis confirmed that all coatings met FDA guidelines for HA coatings. An unspecified FDA parameter, porosity was found to range from 5-15%. Mechanical testing of the bone-implant interface demonstrated large variation in the performance of the coatings. However, further evaluation of two of the coatings did not demonstrate variations in mechanical characteristics. The histologic findings confirmed the mechanical testing results. The coatings which demonstrated the best mechanical characteristics had excellent bone apposition and uniformity and maintenance of the HA coating at all time periods upon histologic evaluation. Conversely, the coatings which demonstrated inferior mechanical characteristics demonstrated variable amounts of bone apposition and moderate to severe coating degradation and breakup. Cell-mediated osteolysis was observed in regions of severe coating degradation, and particle migration was noted in regions far from the interface. It was hoped that the four coatings would behave similarly as they all met current FDA guidelines. The only parameter which differed significantly among the coatings was coating porosity. Our results indicate that coatings with large porosities were associated with increased coating degradation and poor mechanical performance and osteolysis at the bone-coating interface.

Alloys↗
PubMed1995

Effects of indomethacin on biologic fixation of porous-coated titanium implants.

The effect of perioperative administration of indomethacin on attachment strength and bone growth into porous-coated titanium implants was evaluated in the canine transcortical plug model. Various drug administration protocols simulating clinical use of indomethacin were studied. These included chronic treatment (starting 2 weeks prior to surgery), treatment immediately after surgery, and treatment 3, 6, 9, and 18 weeks following surgery. Indomethacin therapy was continued until sacrifice at 3, 6, 12, 18, or 24 postoperative weeks. Push-out testing was performed to determine the maximum bone-implant interface shear strength, and quantitative histologic analysis was used to determine percentage of bone ingrowth. When indomethacin was administered chronically or immediately after surgery, a statistically significant decrease in bone-implant interface attachment strength was seen at 3 postoperative weeks but not at later periods. No adverse effect was observed in any group after the 3-week period. Quantitative histologic analysis demonstrated no significant differences in percentage bone ingrowth among any of the treatment protocols at 3 or 6 weeks after surgery. No significant difference was observed between any of the groups at 18 or 24 weeks. The results of this study suggest that perioperative administration of indomethacin does not significantly affect attachment strength or bone ingrowth into porous-coated implants except at early periods, in which cases a transient decrease in attachment strength occurs.

Animals↗
PubMed1995

Combination total lymphoid irradiation and low-dose corticosteroid therapy for progressive multiple sclerosis.

Total lymphoid irradiation (TLI) has been reported to delay deterioration in patients with progressive multiple sclerosis and other autoimmune disorders. METHODS--In an open trial, the effect of TLI combined with a one year course of low dose prednisone was compared to the effect of sham TLI and TLI only in a prior double-blind study of patients with progressive multiple sclerosis. RESULTS--Twenty-seven patients receiving TLI combined with corticosteroids had significantly greater lymphocytopenia in the year post-therapy than those receiving TLI only or sham TLI and Kaplan Meier product-limit survival analysis showed significantly less progression in the TLI plus steroid group over 4 years of follow-up. No difference in lymphocytopenia or progression was found with TLI plus corticosteroid therapy when the spleen was removed from the field of irradiation. CONCLUSION--These results lend further support to the hypothesis that TLI may be effective in progressive MS, and indicates that adding low-dose prednisone may enhance this effect. The study also suggests that TLI may be equally effective whether or not the spleen is irradiated.

Adult↗
PubMed1995

Evidence for multiple sclerosis as an infectious disease.

Evidence for a viral cause of multiple sclerosis (MS) is indirect since no infectious agent has been reproducibly isolated from MS tissues nor has viral genome or antigen been consistently identified. The occurrence of spontaneous human and animal models of demyelination, serologic studies, and epidemiologic data provide persuasive circumstantial evidence for an infectious trigger in this disease. Potential mechanisms for viral induced demyelination include persistent infection of host tissues or immune mediated organ damage either in the presence or absence of the infectious agent. Any proposed viral candidate should cause demyelination in animals or man and the pattern of infection should be consistent with the unique geographic features of MS epidemiology. In addition, serologic studies should support an infection by the agent and/or viral genome should be detected in MS tissues. At this time no virus can be unequivocally linked to MS but cumulative evidence is more supportive of canine distemper virus than other viruses.

Animals↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗