Biomedical subjects

S G Lynch

Publications and source records attributed to S G Lynch.

9 recordsLinked to original sources

PubMed1997

Relationship of the antispasticity effect of tizanidine to plasma concentration in patients with multiple sclerosis.

BACKGROUND: Spasticity is a serious problem in multiple sclerosis (MS) and many patients do not achieve a satisfactory response to currently available oral antispasticity drugs. Tizanidine hydrochloride, an alpha 2-noradrenergic agonist, has been shown to have an antispasticity effect in single center trials of patients with MS. OBJECTIVE: To compare plasma concentrations of tizanidine with objective measures of muscle tone in patients with MS with moderate to severe spasticity. SETTING: Ten centers, all tertiary referral centers for the specialized treatment of patients with MS, in the United States and Canada. DESIGN: A randomized, double-blind, placebo-controlled, dose-response study of tizanidine hydrochloride (8 or 16 mg). PATIENTS: One hundred forty-two patients with spastic MS who were not taking any interfering medication, such as an antispasticity drug or other alpha-noradrenergic agonist, entered the trial. RESULTS: Tizanidine treatment reduced muscle tone significantly, as shown by improved Ashworth scores and increased knee swing amplitude recorded by the pendulum test, both of which correlated significantly with plasma concentration. Placebo had no significant effect on muscle tone. Dizziness, drowsiness, dry mouth, and fatigue were reported most often in the group treated with tizanidine at peak plasma concentration. CONCLUSIONS: Tizanidine reduces spasticity in MS, and both therapeutic effects and side effects are related to the plasma drug levels.

Adrenergic alpha-Agonists↗

PubMed1996

Multiple sclerosis.

Multiple sclerosis is a chronic disease that begins in late adolescence or adulthood. It is highly variable in its expression and severity. It is believed to be autoimmune in nature. The cause is unknown; both genetic and environmental factors have been implicated in the pathogenesis. MS generally presents with the acute or subacute onset of neurologic abnormalities that may wax and wane over many years. Diagnosis is generally made by means of observation of the clinical course in conjunction with a neurologic examination and laboratory tests. These tests may include magnetic resonance imaging of the head and spine, lumbar puncture, and evoked potentials. Treatment is based on general supportive care, the use of corticosteroids for relapses, and symptomatic management of ongoing problems. The frequency of relapses can be reduced with interferon-beta (Betaseron). Copolymer 1 and interferon-beta la are being evaluated by the U.S. Food and Drug Administration for approval for use for reduction in the frequency of relapses in relapsing-remitting MS. Treatment of chronic progression is often attempted with immunosuppressive agents such as corticosteroids, azathioprine, and cyclophosphamide. Use of other agents is being investigated.

Adolescent↗

PubMed1996

Desferrioxamine in chronic progressive multiple sclerosis: a pilot study.

Chronic progressive Multiple Sclerosis is refractory to many conventional treatments. We performed a pilot study testing desferroxamine (DFO) as a candidate in the treatment of chronic progressive Multiple Sclerosis. DFO was given daily by 8 h subcutaneous infusions at a dose of 2 grams daily for 7 days, followed by 1 gram daily for 7 days. Eighteen of 19 individuals completed the full dose of 21 grams. One patient was unable to complete the course due to nausea. No acute deterioration of neurological status was seen during the administration of DFO. No worsening of vision or hearing was noted except that the one patient who was unable to tolerate the medication had a transient reduction in hearing. All patients had a local redness at the injection site. None of the patients had any sudden worsening during or shortly after the treatment. This pilot study suggests that DFO is relatively well tolerated by Multiple Sclerosis patients when given in a short course of therapy.

Adult↗

PubMed1995

Testing lazaroids U-74389G and U-83836E for therapeutic value in experimental allergic encephalomyelitis in the Lewis rat.

Reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) are toxic molecules that are thought to play a pathogenic role in many disease states, and data from prior studies indicate a role for ROI and RNI in the pathogenesis of experimental allergic encephalomyelitis (EAE). ROI and RNI can elicit tissue damage by initiating the chain reaction of lipid peroxidation. Lazaroids are a series of compounds that have been shown to interrupt lipid peroxidation. In the present study, the lazaroids, U-74389G and U-83836E, were administered to Lewis rats with EAE in order to evaluate their therapeutic effectiveness. Several different doses and administration routes, which were based on the manufacturer's (Upjohn) recommendations and a prior experimental study, were employed: 1) intraperitoneal injection (IP), 1mg drug/kg body weight, 1x/day from 7-18 days postencephalitogen injection (diseases onset approximately 9 day), male; 2) IP, 1mg/kg, 1x/day from 0-18 days, male; 3) intravenous (IV) cannula, 3mg/kg, 2x/day from 7-18 days, female; 4) IV cannula, 3mg/kg, 2x/day from 7-18 days, male; and 5) IV cannula, 10mg/kg, 2x/day from 7-18 days, female. The weights and clinical signs were evaluated on a daily basis. In all treatment regimens, there was an absence of a statistically significant difference between the vehicle-treated animals and the two groups of drug-treated animals. These data imply that lipid peroxidation may not be an effective therapeutic site in EAE. It is important to note that there are several different types of EAE and our study only explored the EAE model in the Lewis rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Usher's syndrome and multiple sclerosis. Review of an individual with Usher's syndrome with a multiple sclerosis-like illness.

We describe an individual with Type I Usher's syndrome and a multiple sclerosis-like illness. MRI scan showed vermian atrophy on T1-weighted images and multiple white matter lesions in the periventricular areas on T2-weighted images. Although MRIs demonstrating increased signal intensity on weighted images are reported in some individuals with Usher's syndrome, the cerebrospinal fluid findings are not described in these cases. In the present case, oligoclonal bands were present in the spinal fluid. The possibility of a linkage between the two diseases is raised.

Adult↗

PubMed1992

Discordance of the T-cell receptor alpha-chain gene in familial multiple sclerosis.

We studied restriction fragment length polymorphisms of the T-cell receptor alpha-chain (TCR alpha) gene in DNA obtained from 99 individuals of 14 multiplex families with multiple sclerosis (MS). Thirty-four family members had definite MS and two had probable MS. Six normal family members had abnormal cranial MRIs. Linkage analysis utilized constructed haplotypes of EcoRV, Sst I, and Taq I polymorphisms. With penetrance values from 0.1 to 0.7, and scoring the normal individuals with abnormal MRIs as either unknown or affected, LOD scores were between -3.16 and -7.95 for the autosomal dominant model. For the autosomal recessive model with a penetrance range from 0.1 to 1, the LOD scores ranged from -6.77 to -23.08. These findings do not support a direct role of TCR alpha in the inheritance of MS.

Adult↗

PubMed1992

Acute VIth cranial nerve dysfunction in multiple sclerosis. Evaluation by magnetic resonance imaging.

VIth nerve palsy is not frequently considered a presenting sign of multiple sclerosis (MS); however, MS has been documented as a fairly common cause of VIth nerve dysfunction. In the present study we have evaluated the clinical features and magnetic resonance imaging (MRI) findings in four MS patients with acute VIth nerve palsy. Diplopia as a result of acute VIth nerve palsy was the prominent symptom leading to the diagnosis of MS in all of the individuals. Other signs specifically localizing to the ipsilateral brainstem were absent in these patients. Cranial MRI revealed multiple white matter lesions with a periventricular predominance in all four patients and pontine white matter lesions in three of the patients. These lesions were either adjacent to the VIth nerve nucleus or involved the fasciculus of the VIth nerve or both.

Abducens Nerve↗

PubMed1991

Discordance of T-cell receptor beta-chain genes in familial multiple sclerosis.

Restriction fragment length polymorphisms of the T-cell receptor beta-chain gene were studied in DNA obtained from 96 individuals from 14 multiplex families with multiple sclerosis (MS). Thirty-four family members had definite MS and two had probable MS. Five normal family members had abnormal findings on cranial magnetic resonance imaging (MRI) scans. Linkage analysis was performed using the BglII and the KpnI polymorphisms. With penetrance values from 0.1 to 0.7, and altering the scoring of the normal individuals with abnormal findings on MRI scans from "unknown" to "affected," log of the odds scores between -4.59 to -12.76 were found for the autosomal dominant model. For the autosomal recessive model with a penetrance range from 0.1 to 1.0, the LOD scores ranged from -8.20 to -32.98. These findings do not support a direct role of T-cell receptor beta-chain gene in the inheritance of MS.

Alleles↗

PubMed1990

MRI in familial multiple sclerosis.

We obtained cranial MRIs of 76 individuals from 13 MS multiplex families. Thirty-one MS patients and 45 normal family members participated in the study. Twenty-eight of the 31 individuals with definite or probable MS had multiple white matter lesions by MRI. Thirty-five normal family members had normal MRIs, and 10 had abnormal studies. Four normal individuals under age 40 had abnormal MRIs. Three had multiple white matter lesions. The 4th had a single small white matter lesion in the left centrum semiovale. Six normal individuals over age 50 had multiple white matter lesions. Although diffuse white matter lesions in individuals over age 50 should be interpreted with caution, these lesions in individuals under age 40 with no history of underlying medical illness are suggestive of demyelination. The results of the present study indicate that subclinical MS may be present in apparently normal members of multiplex families.

Adult↗