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Biomedical subjects

S D Cook

Publications and source records attributed to S D Cook.

At least 145 records · Page 8Linked to original sources

Serum soluble interleukin-2 receptor levels in chronic progressive, stable and steroid-treated multiple sclerosis.

Serum levels of the soluble interleukin-2 receptor (sIL-2R), an indicator of T cell activation, were significantly elevated in chronic progressive MS (CPMS) patients, clinically stable MS patients and in patients with other neurological diseases (OND) as compared to healthy controls. Levels of sIL-2R in steroid treated CPMS patients were markedly lower than in untreated CPMS patients and were comparable to healthy controls. Thus, systemic T cell activation occurs in MS during clinically stable and progressive disease stages and in other neurological disorders. The ability of oral corticosteroids to depress serum sIL-2R levels in vivo may be one mechanism by which they exert their therapeutic effect.

Adult↗

Latency-associated transcripts in corneas and ganglia of HSV-1 infected rabbits.

Herpes simplex virus (HSV) establishes latent infection in the sensory neuron and possibly in non-neuronal tissue, particularly the cornea. During latency only one region of the HSV genome is transcribed, producing RNAs known as latency associated transcripts (LAT). The gene for LAT overlaps with the HSV gene for the protein ICPO in the downstream regions of both genes. Latency can occur in the absence of LAT. This study reports the detection of ICPO/LAT and thymidine kinase (TK) gene fragments by the polymerase chain reaction in DNA extracted from the corneas and trigeminal ganglia of latently infected rabbits. Both genes were detected in four of four trigeminal ganglia tested and in three of five corneas tested. More importantly, this study reports the first detection of LAT in RNA extracted from 9% of corneas from latently infected rabbits (n = 22) by the polymerase chain reaction. LAT was detected in RNA from 100% of the corresponding trigeminal ganglia (n = 22). Although LAT is not essential for latency, it remains the only known molecular marker for latent HSV infections. Detection of LAT in these rabbit corneas suggests that HSV latency may occur in this non-neuronal tissue and that reactivation from non-neuronal tissue may occur at a low frequency in animals in which HSV latency has been established.

Animals↗

Biomechanical evaluation of the anterior drawer test: the contribution of the lateral ankle ligaments.

The contributions of the lateral ankle ligaments to resisting anterior-posterior displacement of the talus were evaluated in eight unembalmed cadaveric ankles. While holding the distal tibia fixed, loads of 150 N were applied to the talus in the anterior and posterior directions in the neutral, dorsiflexed, and plantarflexed positions using an hydraulic test system. Tests were performed on the intact specimens then after sequential sectioning of the lateral ligaments of the ankle. Under strictly anteroposterior loading and without an axial (weight-bearing) load applied, no single ligament could be isolated as having a dominant stabilizing function.

Ankle Joint↗

Increased free light chains in the urine from patients with multiple sclerosis.

We quantitated free kappa (kappa) and lambda light (L) chains in coded urine specimens from subjects with clinically definite multiple sclerosis (MS) (N = 56), other neurologic diseases (OND) (N = 30), and age-matched normal controls (N = 28). Urine from MS patients showed statistically significant increases in free L chains compared with the other groups, although there was overlap between MS patients and OND patients. The ratio of kappa/creatinine was significantly greater in the relapsing-remitting MS group than in patients with clinically stable MS, OND, and normal controls. Elevated free L chains were usually independent of urinary albumin and beta 2-microglobulin levels. Serial studies showed that urinary free kappa/creatinine ratios were elevated during periods of clinical worsening in seven of eight MS patients and subsequently decreased during clinical recovery. The measurement of free L chains in urine obtained at intervals from MS patients may be useful as a marker to monitor disease activity.

Albuminuria↗

Clinical correlation with serum-soluble interleukin-2 receptor levels in Guillain-Barré syndrome.

In patients with Guillain-Barré syndrome (GBS) soluble interleukin-2 receptor (sIL-2R) levels were elevated compared with those of patients with other neurologic diseases (OND), and of healthy controls. Smaller increases in sIL-2R levels occurred in OND patients compared to healthy subjects. Monitoring of GBS patients clearly demonstrated that decreases in sIL-2R levels correlated with clinical recovery. Thus, T-cell activation may be relevant in the pathogenesis of GBS.

Central Nervous System Diseases↗

Fatigue failure of noncemented porous-coated implants. A retrieval study.

The causes of mechanical failure of five noncemented porous-coated components were studied. There were two cobalt-chromium alloy and three titanium alloy implants which fractured after 12 to 48 months. The implants included one acetabular component, and one femoral condylar, one patellar and two tibial components. Examination of the fractured surfaces revealed fatigue to be the mechanism of failure in all cases. The porous coating and the processes required for its fabrication had resulted in weakening and reduction of substrate thickness. Additional factors were stress concentration due to limited, localised bone ingrowth, and some features of the design of the implants.

Aged↗

Early clinical results with the hydroxyapatite-coated porous long-term stable fixation total hip system.

The design and early clinical results with uncemented porous-coated long-term stable fixation anatomic and midstem total hip systems (Implant Technology, Inc, Secaucus, NJ) are described. In an ongoing Food and Drug Administration-approved Investigational Device Exemption-Premarket Approval Program, a random selection method is used to determine patients receiving implants with a hydroxyapatite (HA) coating applied to the porous surface and those receiving uncoated implants. The early clinical results with the HA-coated systems show them to appear superior to the uncoated systems. A greater percentage of patients with HA-coated systems have clinical scores in the excellent to good range, which is primarily a reflection of less prostheses-related pain. Radiographically, all components appear well fixed, with evidence of bone ingrowth. The HA-coated systems have a decreased incidence of radiolucencies, particularly in proximal zones.

Chromium Alloys↗

Enhanced bone ingrowth and fixation strength with hydroxyapatite-coated porous implants.

The effect of a hydroxyapatite (HA) coating on the interface attachment strength, rate of development of attachment strength, and degree of bone ingrowth of porous implants was investigated. Implants with ideal surgical fits and those having interface gap spaces were evaluated using femoral transcortical and intramedullary models. The application of a thin HA coating to porous implants significantly enhanced both interface attachment strength and bone ingrowth. The rate of development of interface strength and bone ingrowth was also more rapid with the HA-coated system. There was no evidence of any disruption, loss, or resorption of the HA coating.

Animals↗

Dysgammaglobulinemia in steroid-dependent optic neuritis: response to gammaglobulin treatment.

At the age of 12, a prematurely born boy with an otherwise unremarkable past medical history developed bilateral optic neuritis associated with transverse myelopathy. Over the ensuing 3 years, recurrent bouts of optic neuritis OU, with dyschromatopsia, and acuity and field loss (arcuate, central, and paracentral scotomas) were controlled with increasing doses of corticosteroids. However, the patient became steroid-dependent and experienced recurrent optic neuritis during multiple attempts at tapering the steroids. He developed optic atrophy and steroid complications, including cushingnoid features and growth maturation delay. Immunoglobulin G subclass 2 and 3 deficiencies were the only serologically detectable abnormalities. Administration of intravenous gammaglobulin (25 g monthly) allowed discontinuation of steroids without further ophthalmic or neurologic disease. Following steroid withdrawal and institution of gammaglobulin, the patient grew 6 inches within 2 years, regaining his vision, retrieving his stature, and normalizing his psychosocial development.

Adolescent↗

Experimental coating defects in hydroxylapatite-coated implants.

Defects in hydroxyapatite (HA)-coated metallic implant systems, including cracks, flakes, or scratches, may occur at the time of surgery or in time because of in vivo loading. Such defects may affect the bone-implant interface response because of increased local metallic corrosion and ion release. Using a canine transcortical push-out model, the interface mechanics and histology of HA-coated titanium and cobalt-chromium-molybdenum alloy implants with and without coating defects were evaluated. The coating defects extended through the HA material to the underlying metallic substrate. Interface mechanical testing and undecalcified histologic techniques were used to evaluate differences in interface response at three, five, six, ten, 12, and 32 weeks postimplantation. There were no statistically significant differences between the HA-coated implants with and without defects for either interface shear strength or stiffness; however, both HA-coated implant types developed significantly greater interface strength and stiffness when compared to uncoated metallic implants. Histologically, in all areas away from the defect, a progression to nearly complete mineralization of osseous tissue directly onto the HA-coated surface was observed with no interpositional fibrous tissue layer. At early time periods (up to six weeks) in the area of the coating defect, bone apposition and mineralization appeared to stop at the edge of the HA coating. At later time periods (greater than ten weeks), the area of the defect was filled with mineralized osseous tissue in approximately one-half of the specimens. A thin fibrous interpositional layer was observed at the interface of the exposed metal substrate.

Analysis of Variance↗

Ocular herpes simplex virus reactivation in mice latently infected with latency-associated transcript mutants.

A mouse model for ocular reactivation of herpes simplex virus type 1 (HSV-1) was modified and used to study the effect of strain difference on the frequency of ocular HSV reactivation. Outbred male NIH white mice were immunized with 1.0 ml of anti-HSV serum with a neutralizing titer of 1:400 24 hr before infection and bilaterally infected at 10(5) plaque-forming units/eye with one of three HSV-1 strains: 17 Syn+, LAT+ (XC-20), or LAT- (X10-13). Latency-associated transcripts (LAT) are produced by strain 17 Syn+ and LAT+ but not by LAT-. The primary infection was monitored by ocular swabbing for HSV. Reactivation was induced by intravenous (i.v.) injection of cyclophosphamide (5 mg) followed 24 hr later by i.v. dexamethasone (0.2 mg). These drugs significantly reduced the white cell count between 0 and 6 days post-administration. The eyes were swabbed for 7 consecutive days to monitor reactivation, and HSV-1 reactivation was induced at the following frequencies in individual eyes: 17 Syn+ (32.5%), LAT+ (18.5%), and LAT- (2.5%) (P less than or equal to 0.002). Co-culture of trigeminal ganglia was done, and random isolates were checked to ascertain their identity. The HSV was recovered from individual trigeminal ganglia at the following frequencies: 17 Syn+ (83%), LAT+ (100%), and LAT- (67%) (P less than or equal to 0.091). These results confirm that the mouse can be used as a reactivation model for ocular HSV infection and that the presence of LAT facilitates reactivation in vivo in the mouse.

Animals↗

Inflammatory response in retrieved noncemented porous-coated implants.

One hundred forty-six noncemented porous-coated hip and knee implants retrieved from 97 patients were evaluated histologically for the type, amount, and anatomic distribution of tissue ingrowth. The degree of inflammatory cell infiltrate present was also evaluated and the predominant cell type was identified. An inflammatory infiltrate was present in the components of 21 of 97 patients (22%). In 16 of the 21 cases the infiltrate was lymphocytes and histiocytes with a minor population of plasma cells. One of the remaining five cases had a predominately plasma cell reaction, and the other four had significant populations of plasma cells. Vascular proliferation was observed in nine of the 21 cases. Bone ingrowth was present in ten of the 21 cases. A 38% incidence of removal for persistent pain was present in cases with an inflammatory infiltrate. Seventeen of 87 patients (20%) with cobalt-chromium devices and four of ten patients (40%) with titanium devices were identified as having an inflammatory infiltrate. The origin of the inflammatory infiltrate is unclear. All patients with inflammatory infiltrates had noninfected implants, which were not loose roentgenographically or clinically at the time of removal. Hypersensitivity and allergic responses to metal ions may produce such infiltrates. It is impossible, however, in the present study to definitively determine the etiology of the infiltrates.

Adult↗

Decreased suppressor-inducer T lymphocytes in multiple sclerosis and other neurological diseases.

Decreased numbers of CD4+CD45R+ suppressor-inducer T cells have been reported in patients with a variety of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis but not in patients with other neurological diseases. We now report our findings using murine monoclonal antibodies and two-color flow cytometric analysis on CD4+CD45R+ T cells in 22 patients with chronic progressive multiple sclerosis, 23 patients with other neurological diseases and 42 normal, healthy controls. Suppressor-inducer T cells were significantly reduced (p less than 0.001) in both patients with multiple sclerosis and other neurological diseases as compared to controls. Both patient populations had elevated helper T cell subset ratios. Thus, our data suggests that decreases in suppressor-inducer T cells may represent a common immunological defect among autoimmune and presumably non-autoimmune neurological disorders.

Adult↗

Performance of retrieved Kuntscher intramedullary rods: improved corrosion resistance with contemporary material design.

Eighteen Kuntscher-type intramedullary rods were obtained after human implantation periods ranging from 1 to 23 years. A clinical evaluation, metallurgical and chemical analyses of each implant were performed. Idiopathic, implant-related pain was the most common reason for removal, but was not related to extent of implant corrosion. When classified as early versus contemporary material compositions, a significant increase in surface corrosion, inclusion content and carbon content were demonstrated in rods made of the earlier composition of stainless steel. Intergranular corrosion was associated with structural design, rather than material microcleanliness or composition. While contemporary intramedullary fracture fixation provides excellent clinical results, the present investigation suggests that the performance of stainless steel implants may be improved through continued refinement of steel composition, careful consideration of structural design and fabrication techniques, and by routine removal of implants at the earliest opportunity.

Biocompatible Materials↗

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↗