Deaths after total lymphoid irradiation for multiple sclerosis.
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Adult↗
Biomedical subjects
S D Cook
Publications and source records attributed to S D Cook.
Is steroid therapy in multiple sclerosis superior to corticotropin therapy?
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Adrenocorticotropic Hormone↗
Detection of latent virus mRNA in tissues using the polymerase chain reaction.
The polymerase chain reaction (PCR) has been adapted for use in gene expression studies. Using this technique, we have been able to specifically detect Herpes simplex virus gene expression in the amount of RNA equivalent to that present in a single mouse ganglion. We have also detected specific transcription of the ras oncogene in biopsies of hepatocellular carcinoma tissue. The single tube RNA PCR reaction should be readily adaptable for use as a rapid screening tool in virus diagnosis; it is capable of detecting several virus infections simultaneously using extremely small tissue biopsies.
Animals↗
Quantitative histologic analysis of tissue growth into porous total knee components.
Histologic and radiographic analysis was performed on 85 porous-coated, uncemented knee components (26 femoral, 34 tibial, and 25 patellar) retrieved from 45 patients for malposition or instability, unexplained pain, late infection, postmortem or postamputation, and posttrauma. No component was clinically or radiographically loose at the time of removal. The average patient age at removal was 62.1 years (range, 39-85 years), and the average time in situ was 12.4 months (range, 2 weeks to 53 months). Radiographs from 31 of the 45 patients (69%) were examined for implant alignment, fit, subsidence, loose beads, and the presence of sclerotic and lucent lines. Histologic and microradiographic sections of the implant and adherent tissue were examined for type, amount, and anatomic location of tissue ingrowth. Overall, 52% of the components showed no evidence of bone ingrowth, 29% showed minimal (less than 2%), 12% showed moderate (2-5%), and 7% showed extensive (5-10%) bone ingrowth. In no case was bone present in more than 10% of the available pore volume of any component. There were no significant differences in the incidence or extent of bone ingrowth among femoral, tibial, and patellar components, nor in the extent of bone ingrowth observed in comparing different implant designs, materials, or porous coating types. When bone ingrowth was observed, the anatomic location was consistent in each type of component. The presence of a lucent line radiographically was indicative of fibrous encapsulation, while a sclerotic line or absence of any radiographic abnormality was seen with both fibrous tissue and bone ingrowth.
Aged↗
Biologic response to hydroxylapatite-coated titanium hips. A preliminary study in dogs.
Hydroxylapatite (HA)-coated and uncoated Ti-6A1-4V alloy femoral endoprostheses were evaluated in adult dogs. The femoral stems had proximal anterior, posterior, and medial pockets of either a commercially pure titanium porous coating or a grooved macrotexture. They also had a medial collar, with an inferior surface pocket of either the porous coating or the grooved macrotexture. HA-coated and uncoated specimens of each type were evaluated. The devices were placed as unilateral hemiarthroplasties in 12 dogs and remained in function for up to 52 weeks. Histologic sections from the uncoated grooved implants showed no direct bone-implant apposition in the proximal regions after up to 10 weeks; the HA-coated grooved implants demonstrated extensive direct bone-coating apposition after 5 weeks. Sections from uncoated porous implants evaluated after 10 weeks demonstrated approximately equivalent in-growth to those sections from the HA-coated devices after 6 weeks. All HA-coated implants demonstrated consistent bone-implant apposition with no fibrous tissue interposition. The HA-coated surfaces were associated with increased bone deposition and proliferation at early implantation periods. In no histologic section examined was there any evidence of deterioration of the HA coating, nor was any separation of the coating from the substrate material observed.
Alloys↗
Detection of herpes simplex virus type 1 gene expression in latently and productively infected mouse ganglia using the polymerase chain reaction.
The polymerase chain reaction (PCR) was employed to detect herpes simplex virus (HSV) sequences in the DNA, and HSV gene expression in total cell RNA, extracted from cervical and trigeminal ganglia of mice during productive and latent infection with HSV-1, strain SC16. Such gene expression was detected in 1 microgram or less of RNA, the quantity anticipated to be present in one or two cervical ganglia. Within the limits of the primers available, gene expression during latency appeared to be restricted to the latency-associated transcript (LAT). The 195 base portion of the LAT amplified by the PCR was sequenced and found to contain several base changes and deletions with respect to published sequences for different HSV strains. These mutations, within the putative open reading frame 2 of the LAT, formed stop or terminator signals, which suggests that the LAT does not act to establish or maintain latency through translation to a protein. The primers for the LAT also amplified a 300 bp fragment from any murine and some other mammalian RNAs. Apart from the oligonucleotide primers, this fragment did not show any homology with HSV.
Animals↗
MHC-restricted autoantigen-reactive T cell clones in multiple sclerosis.
Multiple sclerosis is a demyelinating disease of the central nervous system with genetic, viral and autoimmune characteristics. Myelin basic protein (MBP) is a suspected target autoantigen since it induces experimental autoimmune encephalomyelitis, an animal model closely resembling multiple sclerosis. The disease is mediated by Class II restricted, MBP-reactive T cells possessing the T helper/inducer phenotype. In the present study, we have isolated MBP-reactive T cell clones from the peripheral blood of a chronic progressive multiple sclerosis patient. The clones displayed blastogenic memory responses when rechallenged with the autoantigen and irradiated autologous lymphocytes. MBP recognition by the autoantigen-reactive T lymphocytes was restricted by major histocompatibility complex Class II antigens. Both CD4+8- and CD4-8+ MBP-reactive T cell clones were obtained.
Antigens, Differentiation, T-Lymphocyte↗
Wear characteristics of the canine acetabulum against different femoral prostheses.
We studied cartilage degeneration in 45 canine acetabula after implantation of prostheses with articulating surfaces of low-temperature isotropic (LTI) pyrolytic carbon, cobalt-chromium-molybdenum alloy and titanium alloy for periods ranging from two weeks to 18 months. Gross specimens and histological sections were compared with the nonoperated (control) acetabulum of the same animal. Cartilage articulating with LTI pyrolytic carbon exhibited significantly lower levels of gross wear, fibrillation, eburnation, glycosaminoglycan loss, and subchondral bone change than with metallic surfaces. Survivorship analysis showed a 92% probability of survival for cartilage articulating with LTI pyrolytic carbon at 18 months, as compared to only a 20% probability of survival for cartilage articulating with either of the metallic alloys.
Acetabulum↗
The effects of calcium on bone mineral density in postmenopausal women with colles fractures.
The increased incidence of fracture in postmenopausal women may be attributable, in part, to osteoporosis. Prediposing factors other than age include genetic constitution, physical activity, alcohol and caffeine abuse, and dietary calcium deficiency. A group of 15 postmenopausal women between the ages of 43 and 85 years were analyzed for bone mineral density within 4 weeks of an acute fracture of the distal radius. Dual photon absorptiometry scanning was performed on the first through fourth lumbar vertebrae. Results indicate that bone mineral densities below the fracture threshold (0.965 g/cm2) were seen in 9 of 15 (60%) patients. Each woman was given 1500 mg/day calcium supplementation for 1 year. At 1 year, each woman was contacted for a follow-up bone mineral density analysis. While no significant increase in bone mineral density was seen, calcium supplementation appeared to inhibit further bone loss. The results of this study support previous work which has indicated that supplemental calcium may be beneficial in combatting age-related bone loss.
Adult↗
Roentgenographic measurement of pedicle screw penetration.
Potential complications due to pedicle screw penetration of the anterior cortex include injury to vascular, visceral, ureteral, sympathetic, and neural structures. This study examined the accuracy of lateral roentgenographic techniques in determining actual screw penetration in vertebral levels T12 through S1 of ten unilateral sets of pedicles in five anatomic specimens. A true lateral roentgenogram alone was inaccurate for determining the penetration of the anterior cortex by a pedicle screw. The greatest discrepancy between roentgenographically apparent and actual screw penetration was found at the L4 and L5 levels. Deviation from a true lateral roentgenographic axis resulted in the most pronounced change in roentgenographically apparent screw penetration at L4 and L5. The roentgenographic axes resulting in the closest approximation of actual screw penetrations were 5 degrees and 10 degrees above the true lateral axis for the T12-L3 and the L4-S1 levels, respectively. At 50% apparent penetration, the screw may be safely assumed to not be penetrating the anterior cortex using a true lateral roentgenogram. At 80% apparent penetration, 30% and 10% probabilities of actual screw penetration of the anterior cortex exist at L4 and L5, respectively. At 100% apparent penetration, there is an almost 100% probability that the screw is actually protruding through the anterior cortex.
Biomechanical Phenomena↗
Eye injuries caused by elasticated straps.
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Adult↗
The effect of post-sintering heat treatments on the fatigue properties of porous coated Ti-6Al-4V alloy.
Porous coated Ti-6Al-4V alloy implant systems provide a biocompatible interface between implant and bone, resulting in firm fixation and potential long-term retention via bony ingrowth. In order to achieve an acceptable porous coating structure, the sintering protocol for Ti-6Al-4V alloy systems often requires that the material be heat treated above the beta transus. This transforms the as-received equiaxed microstructure, recommended for surgical implants, to a lamellar alpha-beta distribution, which has been shown to have the worst fatigue properties of the most common structures attainable in Ti-6Al-4V alloy. However, post-sintering heat treatments may be used to improve these properties by producing microstructures more resistant to crack initiation and propagation. This study investigated the influence of microstructural variations on the fatigue properties of porous coated Ti-6Al-4V alloy material. Nonporous coated and porous coated Ti-6Al-4V alloy fatigue specimens were subjected to a standard sintering heat treatment to produce a lamellar microstructure. In addition, two post-sintering heat treatments were used to produce coarse and fine acicular microstructures. Rotating beam (reversed bending) fatigue testing was performed and the endurance limits determined for the noncoated and porous coated microstructures. The values determined were 668 MPa (noncoated as-received equiaxed), 394 MPa (noncoated lamellar), 488 MPa (non-coated coarse acicular), 494 MPa (noncoated fine acicular), 140 MPa (porous coated lamellar), 161 MPa (porous coated coarse acicular), and 162 MPa (porous coated fine acicular). The noncoated coarse and fine acicular specimens displayed an approximate 25% increase over the noncoated lamellar specimens. The porous coated coarse and fine acicular specimens showed an approximate 15% improvement over the porous coated lamellar specimens.
Alloys↗
Measles virus L protein evidences elements of ancestral RNA polymerase.
We have determined the nucleotide sequence of the measles virus (MV) L gene using a cDNA library encompassing the entire MV genome (J. Crowley et al. (1987) Intervirology, 28, 65-77). The L gene is 6639 nucleotides in length, and contains a single long open reading frame that could code for a protein of 247,611 kDa. Both the L gene and in particular the predicted L protein of MV bear substantial homology to their counterparts in Sendai virus and Newcastle disease virus, suggesting that the multifunctional nature of paramyxovirus L proteins imposes strong evolutionary constraints. The predicted MV L protein also contains distinct elements of a postulated ancestral RNA polymerase.
Amino Acid Sequence↗
Sequence variability and function of measles virus 3' and 5' ends and intercistronic regions.
Sequences critical for the activity of the measles virus (MV) RNA polymerase in transcription and replication were analyzed using a MV genomic cDNA library containing overlapping clones encompassing the entire MV genome. Clones corresponding to the 3' and 5' ends of the MV genome were identified and sequenced, and these sequences were confirmed by primer extension experiments. Neither (+) nor (-) strand leader RNAs were detected in MV-infected cell extracts, using high specific activity riboprobes made form these clones. Clones representing each of the MV gene boundaries were also sequenced, and variations including point mutations, insertions, and deletions were noted. Together with the sequence of the MV L gene region, this report completes the sequence determination of the MV genome.
Base Sequence↗
Total lymphoid irradiation for multiple sclerosis.
Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one. Our data suggest that this modified TLI regimen has clinical efficacy and sufficiently low toxicity to make it suitable for investigative immunosuppressive treatment of patients with progressive MS or other non-malignant conditions.
Adult↗
Comparative mechanical analysis of a looped-suture tendon repair.
The in vitro breaking force of a braided nylon looped-suture tendon juncture designed to decrease tying time was compared with the breaking force of the modified Kessler and Bunnell techniques. Repaired with either braided nylon or tetrafluoroethylene, porcine digiti quarti propius tendons were tested to single cycle failure on a MTS hydraulic testing machine. The results showed that the looped-suture technique had a mean breaking force that was statistically indistinguishable from that of the Bunnell technique regardless of suture material. However, the breaking forces for the looped suture and Bunnell techniques were statistically greater for both suture materials when compared with the modified Kessler technique. The resistance to gap formation for the looped suture was found to be intermediate between the Bunnell technique and the modified Kessler technique.
Animals↗
Quantitative analysis of tissue growth into human porous total hip components.
Histologic and radiographic analysis was performed on 36 porous-coated total hip components (22 femoral and 14 acetabular) retrieved from 30 patients. The average patient age was 53.0 years (range, 28-78 years) for femoral components and 56.9 years (range, 28-78 years) for acetabular components. The average time in situ was 13.6 months (range, 2-36 months) for femoral components and 5.5 months (range, 1-18 months) for acetabular components. Fourteen implants were retrieved for instability or dislocation, 12 for late infection, and 8 for persistent pain, and 2 were retrieved after the patient died. Radiographs were reviewed for Singh index, heterotopic bone, implant fit, subsidence, and presence of lucent and sclerotic zones. Histologic and microradiographic sections of the implant and adherent tissue were examined for type, amount, and anatomic distribution of tissue ingrowth. Four femoral stems had no bone ingrowth, 10 had minimal bone growth into the available pore volume (less than 2%), 3 had moderate bone ingrowth (2-5%), and 5 had more extensive bone ingrowth (5-10%). Bone ingrowth tended to occur where the implant made direct contact with the endosteal cortical surface and was rarely seen in proximal metaphyseal bone. Bone ingrowth was completely absent in eight acetabular components, minimal (less than 2%) in three, moderate (2-5%) in two, and more extensive (5-10%) in one and tended to occur adjacent to fixation pegs, spikes, or screws. Radiographic or clinical findings were unreliable in predicting the presence or extent of bone ingrowth in either femoral or acetabular components.
Acetabulum↗
Tissue response to porous-coated implants lacking initial bone apposition.
Although initial bone apposition of a porous-surfaced implant is desirable, it is not always achieved surgically. A model to study the effect of a gap on the quantity and quality of bone growth in both the cancellous and cortical regions has been developed. Implants were surgically placed in the intramedullary canals of adult dogs producing uniform gap spaces 0.0-2.0 mm wide. Histologic and microradiographic evaluations were conducted after 3, 6, and 12 weeks in situ. The results demonstrate that the initial apposition of a porous implant to the surrounding bone surface is not necessary for fixation by bone ingrowth. New bone will grow up to and within the porous structure of an implant even when there is a gap as large as 2.0 mm. However, the rate and degree of maturity and mineralization is enhanced when the gap width is 0.5 mm or less. The amount of bone activity in the cortical region was greater than in the cancellous region at 3 and 6 weeks after operation. After 12 weeks in situ bone growth in gap spaces and into the porous coating was approximately equal.
Animals↗