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Biomedical subjects

S D Cook

Publications and source records attributed to S D Cook.

At least 37 records · Page 2Linked to original sources

Hydroxyapatite-coated total hip replacement.

Biologic attachment of load-bearing orthopedic implants has developed as a response to long-term problems associated with polymethylmethacrylate cement fixation. Although early clinical results of uncemented hip and knee implants have been encouraging, histologic studies of retrieved implants have shown a distinct lack of bone apposition and ingrowth. Hydroxyapatite (HA) coatings applied to metallic implant substrates have been shown to enhance biologic fixation. These results have led to the clinical investigation of the use of HA-coated total hip replacements.

Durapatite

Early clinical results with the hydroxyapatite-coated porous LSF Total Hip System.

The design of and early clinical results with the uncemented porous-coated LSF Anatomic and Midstem Total Hip Systems are described. In a Food and Drug Administration-approved program, a random selection method was used to determine which patients receive implants with a hydroxyapatite (HA) coating applied to the porous surface and which patients receive non-HA-coated implants. The early clinical results with the HA-coated systems appear superior to the non-HA-coated systems. A greater percentage of patients with HA systems have clinical scores in the excellent/good range, which is primarily a reflection of less prosthesis-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.

Durapatite

Tissue growth into porous-coated acetabular components in 42 patients. Effects of adjunct fixation.

Histologic examination was performed on 42 uncemented, porous-coated acetabular components removed for reasons not related to fixation. Included were 20 devices that had fixed pegs or spikes to aid in initial fixation and 22 devices that used screws through the component. The diagnoses and patient ages at insertion, times in situ, and reasons for removal were comparable for the two groups. Bone ingrowth was observed in 28 of the 42 acetabular components (67%). Of the 20 components with pegs or spikes, nine had no bone ingrowth, six had minimal bone ingrowth, four had moderate ingrowth, and one had extensive bone ingrowth. Of the 22 components with screws, five had no bone ingrowth, six had minimal bone ingrowth, six had moderate bone ingrowth, and five had extensive bone ingrowth. Two of the devices with screws also had external threads on the metallic shell; neither had any bone ingrowth, and the two accounted for two of the five devices having no bone ingrowth in this group. Bone ingrowth occurred more frequently, in greater amounts and was more evenly distributed anatomically in cups using screws for initial adjunct fixation. Roentgenographic and clinical findings were unreliable in predicting ingrowth of bone.

Acetabulum

Results of implant retrieval from postmortem specimens in patients with well-functioning, long-term total hip replacement.

The evaluation of postmortem specimens provides a unique opportunity to gain understanding of the interface between host and well-functioning prostheses unavailable from revision specimens that, by nature, are accompanied by the artifacts generated during their removal. The preliminary findings from the relatively limited number of specimens described in this collaborative study demonstrate the value of the effort and are presented to encourage surgeons to participate in this program and to make their patients aware of the value of the information they may provide.

Adult

Search for antibodies to neutral glycolipids in sera of patients with Guillain-Barré syndrome.

Sera from 54 patients with Guillain-Barré syndrome (GBS), 34 patients with other neurological diseases (OND) and 32 healthy controls were tested for antibodies to total lipid fractions and higher neutral glycolipid fractions isolated from human and dog nerves, purified Forssman glycolipid and a panel of purified neutral glycolipids by both an enzyme-linked immunosorbent assay (ELISA) and a thin-layer chromatogram (TLC)-overlay technique. IgM and IgG antibodies to total lipid fractions, as well as to galactocerebroside, ceramide dihexoside, ceramide trihexoside, and globoside were not significantly elevated in the sera of GBS patients as compared to controls. High levels of anti-asialo-GM1 IgG antibodies, however, were detected in 6 of 54 (11%) GBS patients and 1 of 30 (3%) OND patients. Intense reactivity with purified Forssman glycolipid and a number of glycolipid antigens in higher neutral glycolipid enriched fractions of human cauda equina and dog sciatic nerves was noted by TLC-immunostaining in many GBS and control sera. Although the levels of anti-Forssman IgM were significantly decreased in GBS sera compared with normal sera (P less than 0.05) and OND sera (P less than 0.02), the levels of anti-Forssman IgG antibodies were not significantly different. With the possible exception of IgG antibodies to asialo-GM1, our results suggest that serum antibodies against Forssman glycolipid and neutral glycolipids are not significantly elevated in GBS patients and, thus, are unlikely to play an important role in the pathogenesis of this disease.

Animals

Antibodies to sulfated glycolipids in Guillain-Barré syndrome.

Sera from 53 patients with acute Guillain-Barré syndrome (GBS), 15 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 patients with other neurological diseases (OND) and 31 healthy controls were tested for IgM and IgG antibodies to sulfoglucuronyl paragloboside (SGPG) and sulfatide by both an ELISA and a thin-layer chromatogram-overlay technique. Although the mean levels of anti-SGPG or anti-sulfatide antibodies in GBS patients were not elevated compared to controls, the occurrence of anti-SGPG antibodies was more frequent in GBS patients than in controls (P less than 0.02). Acute GBS patients with antibodies to SGPG or sulfatide were clinically indistinguishable from other GBS patients. Our data suggest that elevated levels of antibodies to SGPG could be important in the pathogenesis of neuropathy in some GBS patients.

Animals

Tissue growth into porous primary and revision femoral stems.

The authors studied 45 uncemented porous-coated femoral stems from 45 patients: 35 primary total hip arthroplasties and 10 revisions of either cemented (7) or uncemented (3) femoral components. Histologic sections were examined quantitatively for type, amount, and distribution of tissue ingrowth; these findings were correlated with clinical and radiographic data. Fibrous tissue ingrowth predominated in both groups. Of the primary arthroplasty group, the grade of bone ingrowth in 8 specimens was none, 14 minimal, 6 moderate, and 7 more extensive. In the revision cases, the grade of bone ingrowth in 5 was none, 3 minimal, and 2 moderate. Bone ingrowth was seen more frequently in the distal porous coating, particularly in the revision cases, and most often where direct stem-endosteal canal contact had occurred. While bone ingrowth can occur in uncemented revision stems, it generally appears less abundantly than in primary total hip arthroplasty.

Adult

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

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