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Biomedical subjects

S D Cook

Publications and source records attributed to S D Cook.

At least 91 records · Page 5Linked to original sources
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Improved preservation of human corneal basement membrane following freezing of donor tissue for epikeratophakia.

Current methods for the production of lenticules for epikeratophakia involve rapid freezing, cryolathing, and slow warming of the donor cornea. We have found that this procedure causes structural damage to the epithelial basement membrane in the donor cornea which may subsequently contribute to poor postoperative re-epithelialisation of the implant, leading to graft failure. Endeavouring to overcome these problems, the effects of cryoprotection of donor cornea were investigated, using dimethyl sulphoxide, in conjunction with different cooling and warming rates as part of the protocol for cryolathing. The structural integrity of the epithelial basement membrane zone (BMZ) was then assessed by electron microscopy and by immunofluorescence microscopy using antibodies to types IV and VII collagen, components of the basal lamina and anchoring fibrils respectively, and an antibody to a component of the anchoring filaments. No differences in the pattern of immunostaining for these components were detected, indicating that the composition of the BMZ was unaltered by the different treatment regimens applied. However, electron microscopy showed that preservation of basement membrane ultrastructure was markedly improved when cornea was warmed rapidly rather than slowly, both in cryoprotected and non-cryoprotected tissue. Epithelial cell retention and preservation of stromal architecture appeared superior in cryoprotected samples, while keratocyte structure was heterogeneous throughout the experimental groups. Further work is in progress to assess the efficacy of these protocols in the preservation of keratocyte viability in association with improved basement membrane structure in donor tissue for epikeratophakia.

Basement Membrane↗
PubMed1994

The effect of recombinant human osteogenic protein-1 on healing of large segmental bone defects.

A rabbit ulnar non-union model was used to evaluate the effect of recombinant human osteogenic protein-1 on the healing of a large segmental osteoperiosteal defect. A 1.5-centimeter segmental defect was created in the mid-part of the ulnar shaft of adult rabbits. The defect was filled with an implant containing either recombinant human osteogenic protein-1 or naturally occurring bovine osteogenic protein. The recombinant human osteogenic protein-1 implants consisted of a carrier of 125 milligrams of demineralized, guanidine-extracted, insoluble rabbit bone matrix (the collagen carrier), reconstituted with 3.13, 6.25, 12.5, twenty-five, fifty, 100, 200, 300, or 400 micrograms of recombinant human osteogenic protein-1. Animals that received recombinant human osteogenic protein-1 were compared with animals that received an implant of 250 micrograms of a preparation of naturally occurring bovine osteogenic protein mixed with the collagen carrier. Limbs that served as controls received either the collagen carrier alone or no implant at all. The treated and the untreated defects were examined radiographically and histologically at eight or twelve weeks after implantation. Mechanical testing was performed on six animals. All implants of recombinant human osteogenic protein-1, except for those containing 3.13 micrograms of the substance, induced complete radiographic osseous union within eight weeks. The defects that were treated with an implant of bovine osteogenic protein also healed within this time-period. The bone induced by both types of implants had new cortices with advanced remodeling and marrow elements. Histological evaluation of this new bone at eight weeks postoperatively revealed primarily lamellar bone, with the formation of new cortices and normal-appearing marrow elements. The average torsional strength and energy-absorption capacity of the union induced by recombinant human osteogenic protein-1 was comparable with that of intact bone. The control defects that had been implanted with collagen carrier alone and those with no implant showed no bridging of the defect.

Animals↗
PubMed1994

Evaluation of a hydroxylapatite (HA)/resorbable suture implant for alveolar ridge augmentation.

A new type of hydroxylapatite (HA) particle configuration and implant system for alveolar ridge augmentation was investigated. The PermaRidge implant system was designed to provide better HA particle handling and retention characteristics. Torous-shaped particles were bound together with resorbable sutures into rope-like bundles. The implants were placed as a single unit rather than as individual particles delivered via syringe. Six adult beagle dogs underwent bilateral mandibular tooth extraction. After an eight-week healing period, the animals had PermaRidge implants placed on the right side and HA particles alone placed on the left side. Two animals were killed at each of four, eight, and 16 weeks post-operatively. Radiographically, the PermaRidge implants maintained initial augmentation height throughout the course of the study. There was no compaction of the implant or problems with containment and migration of the HA particles. The HA particles alone demonstrated an approximate 25% decrease in augmentation height with time in situ. The majority of augmentation height was lost within the first four weeks post-operatively. There was also significant particle compaction and migration present in the implant sites. Histologically, the PermaRidge implants demonstrated bone growth into the augmentation, often extending 2-3 particle diameters (2-3 mm). The remainder of the implant was filled with dense connective tissue. There was intimate contact of the ingrown bone with the HA surface. The HA particles alone demonstrated minimal bone ingrowth, with extensive fibrous tissue infiltration. The results indicate that the PermaRidge implant system may provide a viable alternative to HA particles alone for the augmentation of the deficient alveolar ridge.

Alveolar Ridge Augmentation↗
PubMed1994

Use of osteoinductive implants in the treatment of bone defects.

Osteogenic proteins (OPs) are a family of bone matrix polypeptides isolated from a variety of mammalian species, including mouse, rat, bovine, monkey, and man. OPs initiate chondroblastic differentiation in pluripotent mesenchymal progenitor cells, followed by the synthesis of new bone by endochondral ossification. OPs have the ability to induce healing of osteoperiosteal defects in several animal models, supporting a possible therapeutic role in the reconstruction of bone defects. OPs are responsible for the osteoinductive capacity of demineralized bone matrix (DBM) implants, which may also prove to be clinically useful. Preliminary studies using purified, naturally occurring human osteogenic proteins in the clinical management of non-unions have reported promising results. A prospective, randomized clinical trial is currently underway, comparing recombinant human osteogenic protein-1 (rhOP-1) to autograft in the treatment of tibial non-unions. The use of osteogenic protein implants to augment or replace autogenous and allogenous bone grafts will reduce morbidity, and circumvent the risk of disease transmission associated with transplantation.

Animals↗
PubMed1994

Wear and corrosion of modular interfaces in total hip replacements.

Modular components allow for the customization of hip replacements to the individual patient. Modular head-neck components allow for mixed material systems to minimize polyethylene wear as well as provide the ability to vary neck length and head size independent of the stem. Modular interfaces, however, result in an increased susceptibility to interface corrosion and wear debris generation. One hundred eight uncemented femoral stems with modular heads retrieved for reasons other than loosening with modular heads were examined for interface corrosion. In addition, in an effort to quantify the amount of wear debris generated at modular interfaces due to cyclic loading, mechanical testing and electrozone particle analysis was used to study various surface, material, and design combinations. Detectable degrees of corrosion were observed in ten of 29 (34.5%) mixed alloy systems and seven of 79 (9%) single alloy components at an average of 25 months in situ. There was no correlation between presence or extent of corrosion or surface damage with time in situ, initial diagnosis, reason for removal, age, or weight. Stems with corrosion were less likely to have bone ingrowth histologically. The results of mechanical testing showed a significant number of wear particles were generated by all head-neck combinations. The wear debris was almost totally in the size range less than 5 microns. As many as 2.5 million particles were generated the first million cycles loading, with as many as eight million particles generated at ten million cycles. The results indicate that surface preparation and material affect particle generation. Head-neck tolerance mismatch appears to be significantly variable in the number of particles generated.

Alloys↗
PubMed1994

Recombinant human bone morphogenetic protein-7 induces healing in a canine long-bone segmental defect model.

An ulnar segmental defect model was used in adult male dogs to examine the effect of recombinant human bone morphogenetic protein-7 (recombinant human Osteogenic Protein-1 [rhOP-1]; Creative Biomolecules, Hopkinton, Massachusetts) on new bone induction and healing, and to test the mechanical strength of healed 2.5-cm segmental bone defects. The rhOP-1 composites consisted of a carrier of 500 mg of demineralized, guanidine-extracted, insoluble bovine bone matrix (collagen carrier), reconstituted with rhOP-1. Six animals received 1200 micrograms rhOP-1 unilaterally and were killed at 12 weeks for torsional load-to-failure testing using the contralateral side as a control. Two further animals received varying amounts of rhOP-1 bilaterally and were studied histologically. All defect sites receiving rhOP-1 were completely bridged radiographically by eight weeks. A control composite, containing no rhOP-1, failed to induce new bone formation at any time. Histologically, rhOP-1-treated sites examined at 16 weeks had formation of new cortical and cancellous bone, with normal appearing marrow elements in the reconstituted medullary canal. The torsional strength of the rhOP-1-implanted ulnae averaged 72% of control (range, 30-99%). The angular deformation to failure averaged 92% of control (range, 39-122%). The energy absorption to failure averaged 67% of control (range, 27-111%). This study demonstrates the efficacy of rhOP-1 in healing segmental osteoperiosteal defects in a canine model.

Animals↗
PubMed1994

Multiple sclerosis and pregnancy.

Gestation is a period of decreased risk for a relapse of MS, whereas the 3 months postpartum is a period of high risk. Taken together, the pregnancy year may also be a period of higher risk for relapse than non-pregnancy periods. However, the lifetime risk rate does not appear to change because of pregnancy, and on the basis of current retrospective studies, long-term disability is not higher in pregnant women or even women experiencing relapses during the pregnancy year. MS has little or no effect on the course of pregnancy or delivery, although patients with severe MS may have difficulty fully caring for their newborns. The decision to become pregnant should be made by the patient and her husband after they are appropriately informed about the risks involved.

Female↗
PubMed1994

Corrosion and wear at the modular interface of uncemented femoral stems.

We examined 108 uncemented femoral stems with modular femoral heads which had been retrieved for reasons other than loosening. There were detectable amounts of wear and corrosion in 10 of 29 (34.5%) mixed-alloy components and 7 of 79 (9%) single-alloy components after a mean implantation time of 25 months. We found no correlation between the presence or extent of corrosion or surface damage and any of time in situ, initial diagnosis, reason for removal, age, or weight. Stems with wear and corrosion were less likely to show histological bony ingrowth. The interface between the head and stem of modular total hip components is a possible source of ion release and wear debris, but wear and corrosion were totally absent in most specimens. This suggests that this problem could be avoided, and that further research is required to develop manufacturing methods which would minimise such changes.

Cementation↗
PubMed1993

Serologic evidence of previous Campylobacter jejuni infection in patients with the Guillain-Barré syndrome.

OBJECTIVE: To determine if patients with the Guillain-Barré syndrome are likely to have had Campylobacter jejuni infection before onset of neurologic symptoms. DESIGN: A case-control study. SETTING: Several university medical centers. PATIENTS: Case patients met clinical criteria for the Guillain-Barré syndrome between 1983 and 1990 and had a serum sample collected and frozen within 3 weeks after onset of neurologic symptoms (n = 118). Disease controls were patients with other neurologic illnesses (n = 56); healthy controls were hospital employees or healthy family members of patients (n = 47). MEASUREMENTS: Serum IgA, IgG, and IgM antibodies to C. jejuni were determined by enzyme-linked immunosorbent assays. Assays were done in a blinded manner. RESULTS: Optical density ratios > or = 2 in two or more immunoglobulin classes were seen in 43 (36%) of patients with the Guillain-Barré syndrome and in 10 (10%) of controls (odds ratio, 5.3; 95% CI, 2.4 to 12.5; P < 0.001). Increasing the optical density ratio or the number of immunoglobulin classes necessary to yield a positive result increased the strength of the association. The number of patients with the Guillain-Barré syndrome who had positive serologic responses was greatest from September to November (P = 0.02). Male patients were three times more likely to have serologic evidence of C. jejuni infection (P = 0.009); the proportion of patients with the syndrome who had a positive serologic response increased with age. CONCLUSIONS: Patients with the Guillain-Barré syndrome are more likely than controls to have serologic evidence of C. jejuni infection in the weeks before onset of neurologic symptoms. Campylobacter jejuni may play a role in the initiation of the Guillain-Barré syndrome in many patients.

Adolescent↗
PubMed1993

Canine distemper virus L gene: sequence and comparison with related viruses.

We cloned the genomic RNA of canine distemper virus (CDV) and determined the nucleotide sequence of the large (L) protein-coding gene. The L gene is 6573 nucleotides long and contains a single open reading frame coding for a polypeptide of 2161 amino acids (MW 246,354). The precise 5' end of the viral genome consists of a 38-nucleotide leader region. The CDV L protein shows over 77% amino acid similarity with its morbilliform relative measles virus (MV) with nearly 67% of their amino acids conserved. The sequence homology of 11 negative strand viruses L proteins is compared and relatedness was found in the following decreasing order: CDV, MV, Sendai virus, parainfluenza virus type 3, simian virus 5, parainfluenza virus type 2, mumps virus, Newcastle disease virus, respiratory syncytial virus, vesicular stomatitis virus, rabies virus. The consensus sequence of proposed functional domains involved in L gene catalytic activities was well conserved in the CDV L protein.

Amino Acid Sequence↗
PubMed1993

Canine distemper terminal and intergenic non-protein coding nucleotide sequences: completion of the entire CDV genome sequence.

Sequences critical for the transcription and replication functions of canine distemper virus (CDV) RNA polymerase were analyzed. The sequence was obtained from polymerase chain reaction (PCR) products using either c-DNA clones from a genomic library as template or in most instances genomic CDV RNA. Clones coding for the precise 3'- and 5'-ends of the CDV genome were sequenced and the results confirmed by additional PCR experiments. The virtual identity of terminal sequences and spacing at the two noncoding ends speak to the importance of these areas in replication and transcription. The sequence for each of the CDV gene boundaries was defined and all were compared to related viruses. This report completes the sequence determination of the CDV genome.

Base Sequence↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗