Biomedical subjects

T E Feasby

Publications and source records attributed to T E Feasby.

At least 19 recordsLinked to original sources

PubMed1994

Lewis rat EAN is suppressed by the 21-aminosteroid tirilazad mesylate (U-74006F).

Lewis rat experimental allergic neuritis (EAN) was treated with the 21-aminosteroid, tirilazad mesylate (U-74006F). High doses of tirilazad mesylate, begun just before the onset of clinical signs, reduced the clinical and pathological severity of the disease. In rats immunized with a high dose of myelin, axonal degeneration was a major pathological feature. Tirilazad mesylate reduced the amount of axonal degeneration but had little effect on the other pathological features of EAN, such as inflammation and demyelination. Tirilazad mesylate may block axonal degeneration by inhibiting lipid peroxidation of axonal membranes. Inhibition of axonal degeneration is an important goal in the treatment of human neuropathies.

Animals↗

PubMed1993

Antigalactocerebroside antibody increases demyelination in adoptive transfer experimental allergic neuritis.

There is suggestive but inconclusive evidence for a contribution of T cells and antimyelin antibodies to the pathogenesis of the Guillain-Barré polyneuropathy. We have studied the potential synergism of cellular and humoral immunity in the adoptive transfer model of EAN. EAN was induced in Lewis rats by injecting varying doses of P2 peptide (SP26)-sensitized T lymphocytes. Disease severity was dose-dependent. The addition of intravenous GC-AB to a subclinical dose of SP26-sensitized T cells resulted in overt clinical disease and markedly enhanced demyelination. Intravenous injection of antibody alone had no effect. We conclude that activated neuritogenic T cells, while entering into peripheral nerves, alter the blood-nerve barrier, which gives circulating demyelinating antibodies access to the endoneurium. The observations support the concept of a synergistic role of T-cell autoimmunity and humoral responses in the inflammatory demyelination of Lewis rat EAN.

Animals↗

PubMed1993

Adoptive transfer of experimental allergic neuritis in the immune suppressed host.

Experimental allergic neuritis (EAN) was induced in normal and irradiated Lewis rats by passively transferring T cells sensitized to SP-26, a peptide fragment of P2 myelin protein. The recipients became sick 4-8 days post transfer and the degree of disability correlated directly with the dose of T cells. Smaller doses caused demyelination of nerve roots and sciatic nerves and larger doses produced more severe demyelination and significant axonal degeneration. Irradiated recipients developed similar clinical EAN and showed macrophage-mediated demyelination despite severe suppression of the host inflammatory response.

Animals↗

PubMed1993

Extreme variability of expression in monozygotic twins with FSH muscular dystrophy.

We describe monozygotic twins who are either discordant or show extreme variability in the expression of facioscapulohumeral muscular dystrophy (FSHD). One twin was severely incapacitated by FSHD. The asymptomatic twin demonstrated equivocal facial weakness on physical examination, but no difference on quantitative myometry when compared with normal controls. High-resolution cytogenetic analysis showed no chromosomal abnormalities. Five polymorphic 4q35 markers known to be linked to FSHD showed identical RFLP patterns, indicating that submicroscopic chromosomal rearrangement is unlikely. We conclude that this set of twins represents an extreme case of variability in the expression of the FSHD gene.

Adult↗

PubMed1992

Obstetrical lumbosacral plexus injury.

Injuries to the lumbosacral plexus during labor and delivery have been reported in the literature for years, but have lacked electrophysiologic testing to substantiate the location of the nerve injury. We report 2 cases with comprehensive electrophysiologic testing which localizes the site of this obstetrical paralysis to the lumbosacral trunk (L4-5) and S-1 root where they join and pass over the pelvic rim. The paralysis may be mild or severe. Small maternal size, a large fetus, midforceps rotation, and fetal malposition may place the mother at risk for this nerve injury.

Adult↗

PubMed1992

Recurrent Guillain-Barré syndrome. Clinical and laboratory features.

The clinical and laboratory features of recurrent Guillain-Barré syndrome (RGBS) were reviewed in 12 patients in whom a total of 32 episodes fulfilled accepted criteria for Guillain-Barré syndrome (GBS). All patients were asymptomatic or only mildly symptomatic between attacks. In a given patient, the time to reach peak deficit from the onset of symptoms, the functional grade at peak deficit and the duration of the intervals between episodes varied considerably and unpredictably from one episode to the next. Analysis of these parameters across the entire group revealed no significant change as the number of attacks increased. The distribution of weakness varied between episodes with the possible exception of features of the Miller Fisher variant which were more constant. Tremor was noted in two patients and enlarged nerves in one patient. There was no evident response to immunosuppressive therapy. Results of cerebrospinal fluid (CSF) analysis and nerve conduction studies during recurrences were those expected in typical monophasic GBS. On nerve biopsy, onion bulb formations were sometimes observed after several recurrences. The following characteristics of RGBS may be sufficiently distinctive from those of chronic relapsing polyneuropathy to justify their nosological separation: rapid onset of symptoms with subsequent complete or near complete recovery, high incidence of an antecedent illness, lack of an apparent response to immunosuppressive therapy and normal CSF protein levels at the onset of a recurrence.

Adolescent↗

PubMed1992

Detection of hereditary motor sensory neuropathy type I in childhood.

Clinical signs and slowed motor nerve conduction velocities were found in 17 of 36 children under 10 years of age who had one parent with hereditary motor sensory neuropathy type I (HMSN I). Four children had slowed conduction velocities at one year or less. Clinical signs were subtle and included pes planus, distal foot wasting, weakness of ankle eversion and dorsiflexion and areflexia. HMSN I can be detected reliably in children, even before one year of age.

Child↗

PubMed1992

Inflammatory-demyelinating polyneuropathies.

Recent advances in the pathogenesis and management of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are presented. These diseases are both diagnosable and treatable. The role of Campylobacter infection preceding GBS and the use of intravenous immunoglobulin to treat CIDP are discussed.

Axons↗

PubMed1991

P2-peptide induced experimental allergic neuritis: a model to study axonal degeneration.

In experimental allergic neuritis (EAN) severity of clinical disease and pathology correlate with the dose of antigen (Hahn et al., Lab Invest 59:115-125, 1988). To avoid axonal membrane contamination of the antigen, EAN was induced with a synthetic peptide, corresponding to residues 53-78 of bovine P2 myelin protein. Severity of EAN correlated with the dose of peptide in the inoculate. The relationship between demyelination, inflammation and axonal degeneration was studied. Low doses resulted in pure demyelination. Axonal degeneration occurred only with high doses of antigen and in association with very active mononuclear inflammation. The role of macrophages in producing axonal damage is discussed.

Animals↗

PubMed1991

Treatment of Guillain-Barré syndrome with anti-T cell monoclonal antibodies.

Three patients with acute Guillain-Barré syndrome were treated early in the course of the disease with OKT3, an anti-T-cell monoclonal antibody. Each patient developed acute lymphopenia with specific depletion of T3-positive lymphocytes. Two patients had continued progression of clinical deficits for eight and 14 days. This suggests that T lymphocytes may not be essential for progression of Guillain-Barré syndrome at this stage of the disease.

Adolescent↗

PubMed1991

Optic neuritis and orbital lesions: lipid-suppressed chemical shift MR imaging.

A derivative of the Dixon method, chopper fat suppression, was used in the magnetic resonance imaging evaluation of 40 patients: 37 with suspected optic nerve lesions, predominantly optic neuritis, and three with orbital lesions. In patients with optic neuritis, the technique was sensitive, allowing detection of 29 of 34 visual-evoked-response-confirmed lesions on T2-weighted lipid-suppressed images. There were no false-positive studies. Sensitivity for detection of optic neuritis was 89%; specificity, 100%; and accuracy, 86%. The technique was also useful for depicting inflammatory changes in the orbital apex due to fungal abscess and confirming the fatty nature of an extraconal dermoid tumor. A slight increase in noise and mild accentuation of susceptibility effects at interfaces of air, bone, and brain did not degrade images significantly. The chopper-based technique requires only standard imaging time and has usual spin-echo sensitivity. The results are comparable to short-inversion-time inversion-recovery imaging, without the constraints of sequence limitations or artifacts at fat and water interfaces.

Adipose Tissue↗

PubMed1990

Localization of a locus for Charcot-Marie-Tooth neuropathy type Ia (CMT1A) to chromosome 17.

Phenotypic data for 71 genetic markers for members of five Caucasian kindreds were tested for linkage with the autosomal dominant mutations causing Charcot-Marie-Tooth (hereditary motor sensory) neuropathy type I, characterized by markedly reduced nerve conduction velocities. Lod score analysis gave no evidence of linkage to the closely linked chromosome 1 loci SPTA1-FY-F5-AT3 and APOA2. In contrast, these mutations were found to map closely (zeta = 10.828, theta = 0.0) to D17S58, an anonymous segment of DNA from 17p11.2-p11.1, and thus define the CMT1A locus. Segregation information data for an inferred recombinant offspring indicated that the CMT1A locus is probably proximal to MYH2, the locus encoding adult skeletal muscle myosin heavy polypeptide 2, which maps to 17p13. Analysis of the lod scores on a per kindred basis gave no evidence of genetic heterogeneity.

Charcot-Marie-Tooth Disease↗

PubMed1990

X-linked dominant hereditary motor and sensory neuropathy.

Modern techniques have defined the hereditary motor and sensory neuropathies (HMSN) as a genetically heterogeneous group of disorders. This includes a rare variant with X-linked dominant inheritance. We have traced this disorder through 6 generations of a large Canadian kindred; neurological and electrophysiological examinations were performed in 57 family members and nerve biopsies were studied in 2 affected males, early and late in the disease; 42/83 family members were affected. No male-to-male transmission was encountered in 19 sons of affected fathers, whereas all their daughters expressed the disease. Linkage was shown to the DNA loci DXYS1 Z max = 2.87 at theta max = 0.06 and to PGK1 Z max = 1.51 at theta max = 0 (Beckett et al., 1986). The typical clinical features are onset in early childhood, pes cavus, atrophy and weakness of peroneal muscles and intrinsic hand muscles, and sensory abnormalities. Males were severely affected, whereas females had mild or subclinical disease. Electrophysiological observations indicated a substantial loss of distal motor and sensory nerve fibres. Evoked compound muscle action potentials in extensor digitorum brevis were absent or severely reduced in 42% of cases and the peroneal motor nerve conduction velocity was mildly reduced to a mean 36.5 +/- 7.4 m.s-1. Sural sensory nerve action potentials were absent or severely reduced in 75% of those affected. Nerve biopsies showed loss of myelinated and unmyelinated nerve fibres, regenerative sprouting and secondary demyelination. The findings indicate that this distinct variant of HMSN is the result of primary axonal degeneration.

Adolescent↗

PubMed1990

Central lesions in chronic inflammatory demyelinating polyneuropathy: an MRI study.

To determine the frequency of the possible association between chronic inflammatory demyelinating polyneuropathy (CIDP) and MS, we did magnetic resonance imaging (MRI) of the brain in 19 patients with CIDP. Only 1 patient had clinical signs suggestive of central involvement. Seven of the 19 scans showed 2 or more brain "lesions." In 1 case the cause was an infarct and in 5 cases the patients were over 55 years of age and the lesions were not typical of MS. One 38-year-old patient had 2 small subcortical lesions. Typical MS lesions on MRI are uncommon in CIDP.

Adolescent↗

PubMed1988

Motor conduction studies in Guillain-Barré syndrome: description and prognostic value.

The North American study of plasmapheresis in Guillain-Barré syndrome (GBS) included early, standardized electrodiagnostic testing in 210 of the 245 patients. To determine the types of abnormalities and the relation to outcome, we analyzed the prospectively collected motor conduction data obtained during the first 30 days of illness. For each parameter of motor conduction data, means were computed based on institutional normal data. Mean distal motor and F wave latencies commonly were abnormal in these early studies. In univariate analysis, mean compound muscle action potential (CMAP) amplitude from distal and proximal stimulation and mean motor conduction velocity were found to be related to the four predetermined outcome measures. In multivariate analysis of the motor conduction parameters, mean distal CMAP amplitude was the single best predictor of prognosis; other measures did not add to its predictive value. In further multivariate analysis of all factors relating to outcome, mean distal CMAP amplitude was determined to be the most powerful predictor of outcome, followed by plasmapheresis. These two factors were always statistically significant over and above all other variables. Our results indicate that prognostic information can be obtained from motor conduction studies even when performed early in the course of GBS; a mean distal CMAP amplitude of 0 to 20% of the lower limit of normal is associated with a markedly increased probability of a poor outcome. Nevertheless, even in patients with a low mean distal CMAP amplitude, the predicted outcome is improved with plasmapheresis therapy.

Action Potentials↗

PubMed1988

Demyelination and axonal degeneration in Lewis rat experimental allergic neuritis depend on the myelin dosage.

We describe the clinical and pathologic features of experimental allergic neuritis in Lewis rats inoculated with varying doses of myelin, ranging from 0.5 to 20 mg. The clinical scores were assessed daily. On days 18 and 19 or 28 postimmunization, the rats were perfused with fixative and samples of cervical and lumbar roots and sciatic nerves were processed and embedded in Epon. Tissues were examined by light and electron microscopy and the degree of edema, inflammation, demyelination, and axonal degeneration was assessed quantitatively. We found that the severity of clinical and pathologic experimental allergic neuritis correlated positively with the dose of myelin used for immunization. High dose tolerance was not observed. Demyelination prevailed in nerve roots and increased with higher doses of antigen. Accompanying axonal degeneration was seen only with high doses of myelin. The pathology of sciatic nerves differed. Sciatic nerves of rats immunized with 0.5 and 1 mg of myelin were either normal or showed perivenular lymphocytic infiltrates and demyelination, but nerves from rats with higher immunizing doses of myelin showed increasingly severe axonal degeneration. The axonal degeneration in nerve roots paralleled the degree of inflammation and demyelination and may have been a nonspecific product of the inflammatory reaction. However, the much more severe axonal destruction seen in sciatic nerves with high myelin doses was probably due to other pathogenetic mechanisms.

Animals↗

PubMed1987

Complement depletion suppresses Lewis rat experimental allergic neuritis.

Lewis rats immunized with myelin and complete Freund's adjuvant were treated with cobra venom factor (CVF) which depletes the C3 component of complement. CVF given at day 9 delayed the onset of experimental allergic neuritis (EAN) by 2-3 days and when given at days 9 and 12 delayed the onset of EAN by 4-5 days. Lumbar nerve roots of CVF-treated rats had significantly less demyelination than those from control EAN rats.

Animals↗

PubMed1987

Treatment of experimental allergic neuritis with prednisolone.

Experimental allergic neuritis (EAN) in Lewis rats was treated with prednisolone given prophylactically or therapeutically. Rats treated from the time of immunization with myelin or after the establishment of clinical disease improved more rapidly than controls. Treatment at the onset of clinical signs resulted in less severe disease and more rapid recovery. Rats treated just prior to the onset of clinical signs (day 10) did not develop significant clinical disease and appeared to have less inflammation in their nerves and nerve roots on microscopic examination.

Animals↗