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Biomedical subjects

S D Cook

Publications and source records attributed to S D Cook.

At least 19 recordsLinked to original sources

Elevated neopterin levels in Guillain-Barré syndrome. Further evidence of immune activation.

Neopterin is a by-product of guanosine triphosphate metabolism and is produced by macrophages in response to lymphocytic activation. We have studied serum neopterin levels in patients with Guillain-Barré syndrome to obtain further evidence of immune activation in this disease. Serum neopterin levels were significantly elevated in patients with Guillain-Barré syndrome compared with patients with other peripheral neuropathies and multiple sclerosis and with healthy control subjects. Serial analysis demonstrated that as neopterin levels fell, the clinical status of the patients with Guillain-Barré syndrome improved and soluble interleukin 2 receptor levels dropped. Thus, lymphocytic and macrophage activation may play a role in the pathogenesis of Guillain-Barré syndrome.

Adolescent

Hydroxylapatite coating of porous implants improves bone ingrowth and interface attachment strength.

The effect of a plasma-sprayed hydroxylapatite (HA) coating on the degree of bone ingrowth and interface shear attachment strength was investigated using a canine femoral transcortical implant model. Cylindrical implants were fabricated by sintering spherical Co-Cr-Mo particles 500-710 microns in diameter; the nominal implant dimensions were 5.95 +/- 0.05 mm diameter by 18 mm in length. One half of each implant was coated with hydroxylapatite, 25-30 microns in thickness, by a plasma-spray technique. Using strict aseptic technique, the implants were placed through both femoral cortices into defects approximately 0.05 mm undersized. After 2, 4, 6, 8, 12, 18, 26, and 52 weeks, the implants were harvested and subjected to mechanical pullout testing and undecalcified histologic evaluation. The application of the HA coating to porous implants enhanced both the amount of bone ingrowth and the interface attachment strength at all time periods. These differences were statistically significant for the percent of bone ingrowth at the 4-, 6-, 12-, 18-, 26-, and 52-week time periods, and interface shear strength values were significantly different at the 6-, 8-, 12-, 18-, and 26-week time periods. The rate of development of interface strength and bone ingrowth was also more rapid for the HA-coated implants. No evidence of any disruption, mechanical failure, or biologic resorption of the HA coating was observed. The results of the present study--demonstrating a beneficial effect of the HA coating at all time periods--are believed to be due to the use of paired comparisons, which allow assessment of subtle differences that might otherwise have been obscured by normal biological variability.

Analysis of Variance

Effects of Guillain-Barré sera containing antibodies against glycolipids in cultures of rat Schwann cells and sensory neurons.

Serum samples from 52 patients with the acute Guillain-Barré syndrome (GBS), 19 patients with other neurological disorders, and 18 healthy volunteers were tested for cytotoxicity in cultures of rat Schwann cells and dorsal root ganglion neurons. The samples were also examined by enzyme-linked immunosorbent assay for IgG and IgM antibodies against various acidic and neutral glycolipids. Samples from 16 of the 52 (31%) acute GBS patients and from 1 of the 6 patients with chronic inflammatory demyelinating polyneuropathy produced myelin breakdown in culture. Although 10 of the 16 cytotoxic acute GBS serum samples contained anti-glycolipid immunoglobulins, there was no correlation in individual samples between cytotoxic activity and the presence of antibodies against specific glycolipids. While our results do not exclude a role for anti-glycolipid antibodies in the pathogenesis of the acute GBS, the cytotoxic effects of acute GBS serum in cultures of Schwann cells and sensory neurons are probably not due to these antibodies alone.

Animals

Antibodies to acidic glycolipids in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy.

Using an enzyme-linked immunosorbent assay and a thin-layer chromatography-immunostaining procedure, we detected serum antibodies against acidic glycolipids in 36 of 53 patients with Guillain-Barré syndrome (GBS) and 8 of 16 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Although we also found anti-acidic glycolipid antibodies in 4 of 13 patients with other neurological diseases; 2 of 10 patients with multiple sclerosis; 8 of 33 patients with inflammatory, infectious, allergic or autoimmune disorders and 3 of 32 healthy subjects, the levels of antibodies in these controls were much lower than in GBS patients. There were several patterns of reactivity of GBS sera including antibodies to LM1 and HexLM1, GM1 or GD1b or both, various other gangliosides, sulfated glycolipids, and as yet unidentified glycolipids. Sera from 30% of GBS patients had antibodies against two or more antigenically distinct acidic glycolipid antigens. Levels of anti-acidic glycolipid antibodies correlated with clinical symptoms in 9 of 11 GBS patients. While the increased incidence of antibodies to acidic glycolipids in patients with GBS (P less than 0.001) and CIDP (P less than 0.025) compared to controls could be an epiphenomenon, anti-acidic glycolipid antibodies may play a role in nerve injury in some GBS and CIDP patients.

Carbohydrate Sequence

Anti-GM1 IgA antibodies in Guillain-Barré syndrome.

Serum anti-GM1 IgA antibodies were detected in 15 of 53 (28%) patients with the acute Guillain-Barré syndrome (GBS) and in one of 26 (4%) patients with other neurological diseases. Although nine GBS patients had anti-GM1 IgA titers of 1:200 or less, six patients had titers of 1:800 or more. Some GBS patients with anti-GM1 IgA antibodies also had antibodies against GD1b or GM2 or both. The presence of markedly elevated anti-GM1 IgA was associated with a poor clinical outcome at 6 and 12 months following onset of the GBS. The possible pathogenetic role of anti-GM1 IgA antibodies remains to be established.

Antibodies

Anti-MAG IgM paraproteins from some patients with polyneuropathy associated with IgM paraproteinemia also react with sulfatide.

Sera from five of 11 patients with neuropathy associated with IgM paraproteinemia (NAIgMPP) and reactivity against myelin-associated glycoprotein (MAG) also had elevated levels of IgM against sulfatide. Although three patients had anti-sulfatide IgM titers of less than or equal to 1:1000, two patients had titers of greater than or equal to 1:50,000. Absorption of patient serum with sulfatide revealed that anti-MAG IgM paraproteins in two patients with high titer anti-sulfatide IgM crossreacted with sulfatide. Our study is the first to show that some anti-MAG IgM paraproteins crossreact with sulfatide, a major acidic glycolipid of myelin. Moreover, some patients with NAIgMPP have polyclonal anti-sulfatide IgM in addition to anti-MAG IgM paraproteins. Therefore, sulfatide may be a target antigen in some patients with NAIgMPP.

Antibodies

Endophthalmitis at the Bristol Eye Hospital: an 11-year review of 47 patients.

We reviewed data from 47 patients who were treated for endophthalmitis at our hospital during the 11-year period 1980-90. The most common clinical features were hypopyon (75%), diminished vision (72%), ocular pain (68%), discharge (57%), corneal oedema (51%), conjunctival injection (49%), abnormal red reflex (34%), corneal ulcer (32%) and corneal perforation (6%). A total of 54 isolates were obtained from 41 (87%) of the 47 patients. Gram-positive bacteria were more common (72%), than Gram-negative organisms (22%). Two cases were due to fungi, and herpes simplex virus was isolated from one case. The two most common Gram-positive organisms were coagulase-negative staphylococci (25%), and Staphylococcus aureus (11%), while Pseudomonas aeruginosa predominated among the Gram-negative bacteria isolated (15%). Mixed bacterial species were obtained from 29% of the infected patients, including one from whom Vibrio fluvialis was isolated. Predisposing factors included ocular surgery (60%)--mostly for cataract extraction (47%), penetrating trauma (15%) and periocular (15%) or systemic (11%) infections. All patients received antibiotics (generally chloramphenicol and/or a beta-lactamase-stable penicillin plus an aminoglycoside) prior to culture, when treatment was adjusted according to specific aetiological agents. Seventy-nine per cent of patients received topical or systemic steroids. Vitrectomy (diagnostic and therapeutic) was performed on 21% of patients. Sixty-three per cent of culture-positive patients lost vision (no perception of light) in the affected eye, compared to 17% of culture-negative cases (P < 0.05 Fisher exact test). Similarly, a better visual outcome (acuity of 6/12 or better) was associated with coagulase-negative staphylococcal infection than with streptococcal or fungal infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Neurologic testing with somatosensory evoked potentials in idiopathic scoliosis.

A study was undertaken to determine if a somatosensory conduction delay is present in the posterior columns of adolescents with idiopathic scoliosis. Somatosensory evoked potentials were recorded after median and posterior tibial nerve stimulation in 12 adolescent subjects being followed for idiopathic scoliosis with an average age of 14.6 years (range, 12.0-16.6 years). Twelve normal controls matched for age, sex, race, and height underwent identical testing. Evoked potential peak latencies were measured and conduction velocities calculated. Results showed no difference between scoliotics and normal controls. Comparable posterior column conduction velocities were recorded in both groups. If a defect in posterior column function does exist in adolescent idiopathic scoliosis, as previously postulated, it is not reflected by a conduction delay as measured by somatosensory evoked potential testing.

Adolescent

Intravenous gamma globulin in progressive MS.

In an attempt to prevent disease exacerbations, intravenous gamma globulin (500 mg to 2 g/kg) plus methylprednisolone was administered monthly to 14 patients with progressive multiple sclerosis, 11 of whom were steroid dependent. Seventeen exacerbations of disease activity were seen in 11 patients over a mean follow-up period of 7.8 months. Four exacerbations occurred in 3 patients within one month of receiving 1.6 to 2.0 g/kg of intravenous gamma globulin (IVGG). Most exacerbations occurred within 2 weeks of steroids being tapered; thus a steroid sparing effect of IVGG could not be demonstrated. We conclude that IVGG plus methylprednisolone can be given safely at monthly intervals for a prolonged period but in the dosage administered did not prevent exacerbations in 80% of patients with progressive multiple sclerosis.

Adult

Broken intraocular lens during cataract surgery.

A case of planned routine extracapsular cataract extraction is described where surgery was complicated peroperatively by fracture of the posterior chamber lens implant. The technique of lens implantation is discussed.

Cataract Extraction

Rate and types of fractures in corticosteroid-treated multiple sclerosis patients.

In a retrospective study of 103 corticosteroid-treated MS patients, the average rate of fracture events was 3.2% of the patients per year over 7.1 (+/- 5.7 SD) years at risk. Fractures of the ribs, pelvis, hip, or vertebrae occurred in 11 patients and became most common 5 years after starting steroids. Relatively high or low cumulative doses of steroids did not correlate predictably with the occurrence of fractures.

Adrenal Cortex Hormones

Respiratory function in multiple sclerosis. Utility of clinical assessment of respiratory muscle function.

PURPOSE: The aim of this study was to assess the utility of clinical assessment of respiratory muscle weakness in MS. PATIENTS AND METHODS: We studied 40 MS patients who performed pulmonary function tests using standard procedures and measures of respiratory muscle strength. Descriptive clinical indices included a history of detailed neurologic findings, including upper and lower extremity weakness, cerebellar signs, and evidence of cerebral lesions and other clinical signs including dependence in activities of daily living, shortness of breath, weak voice, dysarthria and dysphagia. We devised an index comprised of four clinical signs: the patient's report of difficulty in clearing pulmonary secretions and his report of a weakened cough, the examiner's observation of the patient's cough, and ability to count on a single exhalation. RESULTS: Mean values of TLC (95 percent +/- 14) VC (91 percent +/- 19), and RV (106 percent +/- 34) were normal. By contrast, MVV (68 percent +/- 20), PImax (74 percent +/- 27) and PEmax (51 percent +/- 22) were decreased. Stepwise multiple regression indicated that the best single predictor of expiratory muscle weakness was the index score; the combination of index score, upper extremity weakness, and maximal voluntary ventilation accounted for 60 percent of the variance in PEmax. CONCLUSION: We conclude that clinical assessment is a better predictor of respiratory muscle weakness than spirometry and that a systematic clinical assessment supplemented by respiratory muscle assessment and MVV can uncover subtle respiratory muscle weakness in patients with MS.

Adult

Torsional stability of HA-coated and grit-blasted titanium dental implants.

Hydroxylapatite (HA)-coated and grit-blasted (non-HA-coated) titanium dental implants were inserted into healed extraction sites of canine mandibles. After six weeks, the animals were killed and the implants mechanically tested in torsion to failure. Interface attachment strength, implant/tissue compatibility, integrity of the HA coating, and the location of interface failure were evaluated. Mechanical testing demonstrated an interface torsional strength of 3.98 +/- 0.93 MPa for the HA-coated implants and 2.25 +/- 0.65 MPa for the grit-blasted implants. This represents a 76.9% improvement in the maximum torsional interface strength, and is statistically-significant (p = 0.0004). On qualitative histologic analysis, interface failure was seen to occur primarily at the HA/implant interface, although failure through the HA coating and regions of bone/HA interface failure were observed. The HA-coated implants had bone in direct apposition to their surface with no fibrous tissue interposition. The grit-blasted implants also had regions of direct bone-implant apposition, but these areas were limited to a smaller proportion of the total interface area. There was no evidence of breakdown or change in thickness of the HA coating.

Animals

A comparison of femoral and mandibular animal models for the evaluation of HA-coated implants.

The application of hydroxylapatite coatings promises marked improvement in the rapidity and durability of osseointegration for both dental and orthopedic metallic implants. Standard methods for the in vivo assessment of the performance of experimental implants include canine mandibular and femoral transcortical implantations. This study compared the results of the two procedures by use of similar HA-coated titanium implants. The results indicate that the rapidity of osseointegration and the maximum attachment strength for mandibular dental implants approximate those of the femoral transcortical implants, especially at longer post-operative intervals. We conclude that the two models are comparable for the purpose of evaluating the performance of this type of implant and can be used interchangeably by dental and orthopedic implant designers. HA-coating of titanium implants provides extensive osseointegration in both mandibular and long-bone models, with similar mechanical attachment strengths and histologic appearance.

Analysis of Variance

The use of a new form of allograft bone in implantation or osseointegrated dental implants--a preliminary report.

The use of and early results with a new form of demineralized allograft bone tissue with the immediate placement of a dental implant are described. No occlusive membranes were utilized. GRAFTON Allogeneic Bone Matrix (ABM) is processed from human cortical bone into a thick gel consistency and packaged sterile in disposable syringes. The material was utilized in seven patients with seven implants. New bone formation was noted and, with the exception of two implants with a small amount of thread exposure, complete. It appears that treatment with the bone-grafting material produced clinical results similar to those reported with the use of barrier membranes and may provide an alternative to guided tissue regeneration. Further investigation appears warranted.

Bone Matrix

Biocompatibility and biofunctionality of implanted materials.

The mechanical and chemical properties of metals, such as titanium, titanium-based alloys and cobalt-based alloys, and ceramics, such as Bioglass and calcium phosphate, make them suitable for implant applications. However, several factors affect the biologic response to these implanted materials. The predominant tissue found at the implant interface is affected by implant stability, material biocompatibility, and implant design and implant placement into the surgical site. Improvements in implant design and surface preparation may improve implant longevity and fixation for all implants materials.

Animals