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Biomedical subjects

S D Cook

Publications and source records attributed to S D Cook.

At least 55 records · Page 3Linked to original sources

Spinal cord disease in children with HIV-1 infection: a combined molecular biological and neuropathological study.

An autopsy study was performed on spinal cords from 18 children who died with HIV-1 infection, using standard histopathologic techniques as well as in situ hybridization and immunocytochemistry for HIV-1. Of 16 spinal cords examined by histology, nine had inflammatory cell infiltrates and six had multinucleated cells; both types of lesion are associated with the presence of HIV-1 in central nervous system tissue. HIV-1 type lesions were often present in the spinal cord and brain from the same patient. Pallor of myelin in corticospinal tracts in the cord was present in half of the cases; this change correlated with diffuse myelin pallor in the corresponding brains, but not with the HIV-1 associated changes in the cords. In situ hybridization for HIV-1 nucleic acid sequences gave positive results in seven of 18 spinal cords, with hybridizing signal usually localized to inflammatory cell infiltrates and multinucleated cells. Positive in situ hybridization, on frozen sections, correlated with the presence of HIV-1 associated changes on paraffin sections from the same cases. Immunocytochemistry for p25 core protein of HIV-1, using a monoclonal antibody on frozen sections, was positive in multinucleated cells, macrophages, and microglia. In this series there were two cases of vacuolar myelopathy, one a 30-month-old boy who had concomitant measles virus in the spinal cord grey matter, and the other nine-year-old girl who had severe HIV-1 infection of the cord. Other than the single case of measles virus, there were no opportunistic infections in the cords in this series. HIV-1 frequently involves the spinal cord in children with AIDS, while opportunistic infections are rare. Vacuolar myelopathy occurs in children with HIV-1 infection, although its occurrence is much less frequent than in adults with AIDS.

Acquired Immunodeficiency Syndrome

Antiviral drug sensitivity in ocular herpes simplex virus infection.

Thirty-nine herpes simplex virus (HSV) isolates were assayed for their sensitivity to 10 different antiviral agents. Of these 39 HSV isolates 10 were cultured from recipient buttons obtained at penetrating keratoplasty in patients with inactive stromal scarring due to recurrent herpetic keratitis, 25 were cultured from patients with conjunctival and ulcerative ocular infections, and the remaining four were laboratory strains with known drug sensitivity patterns, thus providing controls for the experiment. All but one of the 35 clinical isolates of HSV were type 1 and all were sensitive to the 10 antiviral agents. A single type 2 isolate from a young man with recurrent conjunctivitis proved to be resistant to a number of the antiviral agents. Since many of the clinical isolates had been exposed to multiple and protracted antiviral drug treatment, it is suggested that antiviral drug resistance in type 1 HSV ocular infection is not a significant problem.

Antiviral Agents

Measles vaccination does not prevent multiple sclerosis.

Twenty-seven young patients with multiple sclerosis (MS) were studied to determine if they had received prior measles vaccination. Fourteen patients whose immunization records were available had received measles vaccine in childhood. Eight other patients gave a history of receiving measles vaccine. These results suggest that infection by measles virus is probably not the sole cause of MS and that, unlike subacute sclerosing panencephalitis and postmeasles encephalitis, MS may not be preventable by measles vaccination given at an appropriate age.

Activities of Daily Living

A comparison of three varieties of noncemented porous-coated hip replacement.

We reviewed 134 primary noncemented porous-coated total hip replacements in 125 patients: 64 were DePuy AML prostheses, 20 were Howmedica PCA and 50 were Implant Technology LSF. The prostheses had been in situ for an average of 36 months, 40 months and 24 months respectively. The average pre-operative Harris hip scores were 38.2 for AML, 33.2 for PCA, and 41.0 for the LSF prostheses. The average postoperative scores were 80.7 for AML, 83.8 for the PCA, and 91.5 for LSF. Thigh or groin pain associated with the prosthesis was present in 30% of AML, 30% PCA and 8% of the LSF cases. The clinical and radiographic review showed better early results with the LSF prostheses than the others; this seemed to be related to the implant design, which provided improved initial stability and more physiological transfer of load.

Adult

Four-year average follow up of cemented PCA total knees: clinical and roentgenographic analysis.

Twenty patients with 25 consecutive primary-cemented Howmedica PCA total knee prostheses were clinically and roentgenographically reviewed. Twenty implants were placed in 16 women and five in four men. The average patient age at surgery was 68.0 years (range, 53 to 82), and average follow up was 51 months. Total knee replacement indication was degenerative joint disease in 21 knees and rheumatoid arthritis in four. Excellent or good results were seen in 22 of 25 knees (88%) at the early follow up examination and 18 of 25 knees (72%) at the most recent follow up examination.

Aged

Pharmacological regulation of the circulation of bone.

A study was undertaken to investigate the reactivity of the circulation of bone and to pharmacologically characterize the receptor populations that may be present in this poorly described vascular bed. The nutrient artery of the tibia in skeletally mature mongrel dogs was cannulated, under direct vision, through a posterolateral operative approach. An extracorporeal circuit was established so that the nutrient artery of the tibia could be perfused in vivo under conditions of constant blood flow. Diverse vasoactive substances were injected into the perfusion circuit in small volumes as a bolus close to the nutrient artery of the tibia. A range of doses of nitroglycerin, acetylcholine, isoproterenol, methoxamine, U46619 (a thromboxane A2 mimic), dibutyryl cyclic AMP, 8-bromo-cyclic GMP, and endothelin-1 were injected in a randomized sequence for each experiment. The antagonists that were used were atropine (a non-selective muscarinic receptor antagonist), ICI 118551 (a selective beta 2-adrenoceptor antagonist), ONO 3708 (a prostaglandin H2/thromboxane A2 receptor antagonist), and prazosin (an alpha 1-adrenoceptor antagonist). The results of changes in bone-perfusion pressure under conditions of constant blood flow indicated that the vascular bed of bone actively responds to various vasoconstrictor mechanisms, whereas vasodilator mechanisms appear to be considerably less active. Intra-arterial injections of nitroglycerin, acetylcholine, and 8-bromo-cyclic GMP resulted in dose-related decreases in bone-perfusion pressure that were weak relative to concomitant changes in systemic arterial pressure. Intra-arterial administration of methoxamine, U46619, and endothelin-1 resulted in a potent dose-related increase in bone-perfusion pressure. The results of intra-arterial injections of isoproterenol and dibutyryl cyclic AMP were surprising; both substances caused a substantial rise in bone-perfusion pressure. The responses to acetylcholine, methoxamine, and U46619 were blocked in a competitive manner after administration of atropine, prazosin, and ONO 3708, respectively.

Acetylcholine

A survey of running injuries in 1505 competitive and recreational runners.

A 33 item multiple choice questionnaire was circulated; completed questionnaires from 1505 runners (1130 male and 375 female) were obtained. Questions focused upon training, injuries sustained, and medical care. Biomechanical imbalances such as leg length inequality appear to be a major contributing factor to running injuries. Correction of an underlying biomechanical defect may be important in the treatment of many running injuries. Female runners were found to be more susceptible than males to stress fractures at higher mileages. The cause of this increased incidence may be attributable to lower bone mineral density levels as a result of hormonal factors. Factors such as running surface, age and stretching techniques do not appear to play a significant part in the pathogenesis of running injuries.

Adult

Clinical and roentgenographic evaluation of bipolar prostheses with noncemented anatomic medullary locking femoral stems.

Fifty-six DePuy anatomic medullary locking femoral bipolar prostheses were reviewed clinically and roentgenographically in 50 patients at an average follow-up period of 30 months (range, 24-71 months). Forty-four of the implantations were in 40 male and 12 were in ten female patients. Forty-five devices were placed in primary operations, while 11 were used in revisions. The overall average age was 53.5 years. The average Harris hip scores for the primary bipolars were 29.8 preoperative and 77.3 postoperative, while the revision bipolars had Harris hip scores of 35.9 preoperative and 75.1 postoperative. Nearly one-half (47%) of all primary and 54% of the revision patients experienced pain to some degree on ambulation. Roentgenographically, all femoral components appeared to be well fixed biologically. Roentgenographic changes occurred with time in both primary and revision prostheses. On roentgenographic zonal analysis of primary prostheses, radiolucencies greater than 1 mm were present most frequently in the most proximal lateral zone and at the distal tip of the prosthesis. Although the use of noncemented bipolar prostheses generally shows acceptable clinical results, noncemented fixed acetabular components with noncemented femoral components produce a more satisfactory clinical result.

Adult

Electromyographic analysis of rowing stroke biomechanics.

Electromyography was used to study muscle activity in the upper and lower extremities and torso during the rowing stroke. Five experienced male rowers were tested while rowing on a Concept II ergometer. In order to fully evaluate the rowing stroke, six phases were utilized to identify the transition points where individual muscles become more active due to body angle or nature of the motion. The results indicate that the strength of an individual muscle is most likely not as important to the rowing stroke as the combined activity of two or more groups of muscles. Thus, in addition to strength, it is of great value to the oarsman to develop technical skill to coordinate his upper and lower body reactions.

Adult

Clinical and roentgenographic evaluation of noncemented porous-coated anatomic medullary locking (AML) and porous-coated anatomic (PCA) total hip arthroplasties.

Eighty-four primary noncemented porous-coated total hip arthroplasties (THAs) in 78 patients were reviewed clinically and roentgenographically at an average follow-up period of 37 months. The average patient age was 51.9 years. Sixty-four Anatomic Medullary Locking (AML) devices were placed in 58 patients, and 20 Porous-Coated Anatomic (PCA) devices were placed in 20 patients. The AML devices had been in situ an average of 36 months (range, 24-49 months), and the PCA devices had been in situ an average of 40 months (range, 29-51 months). The average patient ages were 52.7 and 49.2 years for AML and PCA patients, respectively. The AML devices included three that were fully coated, 59 that were five-eighths coated, and two that were one-third coated. The average preoperative Harris hip score was 38.2 for the AML devices and 33.2 for the PCA devices. The average postoperative Harris hip score was 80.7 for the AML devices and 83.8 for the PCA devices. Pain related to the implant was present in 30% of the AML devices and 30% of the PCA devices. Roentgenographically, no component demonstrated complete radiolucency, and all components demonstrated roentgenographic evidence of bone ingrowth. Roentgenographic changes with time noted for both the AML and PCA devices included: neck roundoff, neck osteolysis, neck corticocancellization, endosteal bone bridging, and distal hypertrophy. On roentgenographic zonal analysis, radiolucency greater than 1 mm was observed most frequently in the most proximal lateral zone and distal tip of the femoral component. The current series of cases, although clinically acceptable, does not support the current widespread enthusiasm for primary noncemented AML and PCA total hip systems. Cemented THA appears to produce superior clinical results, particularly when contemporary cementing techniques are employed.

Adult

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