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Biomedical subjects

G W Ellison

Publications and source records attributed to G W Ellison.

At least 73 records · Page 4Linked to original sources
PubMed1987

Evoked potentials predict the clinical changes in a multiple sclerosis drug study.

Visual, brainstem auditory, and median nerve somatosensory evoked potential (EP) tests were performed annually during a 3-year, double-blind, placebo-controlled study of azathioprine with or without steroids in chronic progressive MS. Treatment-related visual and somatosensory EP changes became statistically different 1 year before corresponding differences were seen in the Standard Neurological Examination scores. The statistical significance of EP changes was substantially greater than seen for changes in other clinical scales. The degree of significance was increased by using EP latency values, rather than simple criteria for change. EPs are sensitive, objective measurements useful in MS therapeutic trials.

Adult↗
PubMed1987

Delta-9-THC in the treatment of spasticity associated with multiple sclerosis.

Marijuana is reported to decrease spasticity in patients with multiple sclerosis. This is a double blind, placebo controlled, crossover clinical trial of delta-9-THC in 13 subjects with clinical multiple sclerosis and spasticity. Subjects received escalating doses of THC in the range of 2.5-15 mg., five days of THC and five days of placebo in randomized order, divided by a two-day washout period. Subjective ratings of spasticity and side effects were completed and semiquantitative neurological examinations were performed. At doses greater than 7.5 mg there was significant improvement in patient ratings of spasticity compared to placebo. These positive findings in a treatment failure population suggest a role for THC in the treatment of spasticity in multiple sclerosis.

Administration, Oral↗
PubMed1986

Cytosine arabinoside induced changes in natural killer and antibody dependent cellular cytotoxicity functions in multiple sclerosis patients.

Five multiple sclerosis patients were treated weekly with cytosine arabinoside (araC) on an escalating dose schedule. The dose was initiated at 50 mg/M2 and then increased once each week by 50 mg/M2 (unless toxicity caused delay). Dosage decisions were based on whether or not the antibody-dependent cellular-cytotoxicity (ADCC) or natural killer (NK) cytotoxicity levels had been reduced to a level more than 2 standard deviations below the control range. Cytosine arabinoside treatment was discontinued in 2 of 5 subjects at doses of 500 mg/M2 due to toxicity. The 3 remaining patients demonstrated sustained reductions in the percentage of FcR+ cells in their peripheral blood. The maximum percentage reductions from the baseline values ranged from 50% to 76%. Concomitant reductions in the NK activity at the same doses ranged from 65% to 83%. ADCC activity in all 3 patients, however, was relatively resistant to suppression. The nadirs for the ADCC activity were only 16% to 44% below the baseline minimum. AraC was shown to reduce the proportion of FcR+ cells and NK cytotoxic activity in preference to ADCC activity.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

Effect of flunixin meglumine on surgical wound strength and healing in the rat.

Forty male adolescent Sprague-Dawley rats were anesthetized and standardized ventral midline laparotomies and uniform-length gastrotomies and typhlotomies were performed. The visceral and abdominal surgically inflicted wounds were closed with 5-0 polypropylene and 4-0 nylon suture, respectively. The rats were allotted into 4 groups (10 rats/group); 2 groups were not given flunixin meglumine (controls) and 2 groups were given flunixin meglumine (1.1 mg/kg of body weight, IM, every 12 hours). On day 5 and again on day 14 after surgery, 1 control and 1 flunixin meglumine-treated group were euthanatized. Tensile strength of the skin and linea alba incisions was determined, using a computerized tensiometer. Gastric and cecal incision bursting strengths were determined, using a pressure manometer. Flunixin meglumine significantly (P less than 0.05) decreased the tensile strength of wounds in the skin and linea alba, but did not affect visceral bursting strength at day 5 after surgery. At day 14 after surgery, a significant difference in wound strength was not found between the flunixin meglumine and control groups in any of the tissues evaluated. Flunixin meglumine had an adverse influence on the inflammatory stage of wound repair, but not on the proliferative stage, when fibroplasia is a major factor in wound strength. Major histologic differences were not found in the incision wounds of flunixin meglumine-treated and nontreated control rats.

Animals↗
PubMed1985

Increased prevalence and titer of Epstein-Barr virus antibodies in patients with multiple sclerosis.

The prevalence and titer of serum antibodies to several Epstein-Barr virus (EBV) antigens were compared among patients with multiple sclerosis, healthy siblings of multiple sclerosis patients, patients with other neurological diseases, and healthy non-blood-related subjects. Serum-cerebrospinal fluid (serum-CSF) pairs were available on a selected number of multiple sclerosis and control subjects. An increased antibody response to EBV antigens was noted rather consistently in the sera of the multiple sclerosis group in comparison with the control groups. A greater number of reduced ratios of serum:CSF IgG antibody to EBV-capsid antigen and antibody to EBV-early antigen components than to adenovirus, a reference or control virus, were found in the multiple sclerosis group. Reduced ratios of these EBV antibodies were detected more frequently or showed a trend in this direction in multiple sclerosis patients compared with the group with other neurological diseases. Our findings extend the results of an earlier report and strengthen the association between EBV and multiple sclerosis.

Adenoviruses, Human↗
PubMed1985

Azathioprine and steroids are not more effective in decreasing multiple sclerosis intra-blood-brain-barrier IgG synthesis than steroids alone.

Intra-blood-brain-barrier IgG synthesis rates and oligoclonal IgG banding patterns were examined in 9 patients with multiple sclerosis who were treated with azathioprine and steroids for 2 to 4.5 years. The IgG synthesis rates of 5 patients were significantly decreased from the pretreatment mean values 1 month after treatment, and their synthesis rates remained at the decreased levels throughout treatment. However, among the remaining 4 patients, the rates exceeded the pretreatment means. This continuous suppressive effect of the combined azathioprine and steroids upon the IgG synthesis rate was similar to that of steroids, suggesting that azathioprine and steroids in combination were not more effective in reducing intra-blood-brain-barrier IgG synthesis than steroids alone. Oligoclonal IgG patterns in all cerebrospinal fluid samples were not significantly altered during the study.

Adrenocorticotropic Hormone↗
PubMed1984

Cytotoxic activity of peripheral blood and cerebrospinal fluid lymphocytes from patients with multiple sclerosis and other neurological diseases: analysis at the single cell level of the relationship of cytotoxic effectors and interferon-producing cells.

The production of interferon (IFN alpha) in relationship to NK and ADCC activity of peripheral blood and cerebrospinal lymphocytes was examined at the single cell level in patients with multiple sclerosis (MS) and other neurological diseases (OND) compared with age- and sex-matched controls. IFN-producing cells were assessed by indirect immunofluorescent scoring of cytoplasmic IFN+ cells. Peak production of cytoplasmic IFN alpha in nylon wool-passed ( NWP ) cells occurred between 5 and 17 hr in vitro under the inductive stimulus of MOLT 4, K562, or antibody-coated Chang liver cells. The proportion of K562- and MOLT 4-induced IFN alpha-positive cells in the total lymphocyte and target-binding cell (TBC) population was significantly lower in MS NWP -peripheral blood lymphocytes (PBL) than in OND and normal controls; this was in direct relationship to a decreased percentage of NK cells in MS PBL. In contrast MS cells responded the same as controls (total IFN+ cells) or higher than controls (IFN+-TBC) after IFN alpha induction by antibody-coated Chang, the ADCC target, in parallel with elevated ADCC activity by MS PBL. MS CSF contained a higher proportion of total IFN+ cells but a similar proportion of IFN+-TBC as their homologous NWP PBL population. In OND CSF, both the percentage of total IFN+ and the percentage of IFN+-TBC were higher than in OND blood and higher than their respective MS CSF populations. The relationship of IFN-producing cells in the central nervous system (CNS) to putative cytotoxic cells is discussed.

Cerebrospinal Fluid↗
PubMed1984

An illness severity score for multiple sclerosis.

A single score is desirable for evaluating progression in clinical trials of MS therapy. Our objective was to develop a more sensitive scoring that would reflect clinical assessment of relative severity of disability. An Illness Severity Score (ISS) was developed as a sum of weights corresponding to ratings of Kurtzke Disability Status Scale and Functional Systems Scales and phase of illness. Weights were computed from clinical comparison of pairs of patients. The score was standardized to have mean 50 and standard deviation 10 in a single clinic population. Score reproducibility (correlation = 0.93) was evaluated by two independent scorings of several patients. The ISS was satisfactory as the primary assessment in a small-scale clinical trial.

Humans↗
PubMed1984

Multiple sclerosis.

The cause of multiple sclerosis is unknown but seems to be multifactorial. Susceptibility or resistance may be genetically determined; something in the environment interacts with the human host at the proper age to cause biochemical and structural lesions in the central nervous system. The systemic immune response and the response of the central nervous system become involved. Although multiple sclerosis cannot yet be cured, many clues are leading to an effective palliative therapy. Suppression or modulation of the immune responses may be the key to developing that treatment. If the environmental agent is one or several viruses, then antiviral regimens will be appropriate. Research must therefore continue at both basic science and clinical levels.

Adrenocorticotropic Hormone↗
PubMed1984

Response to and production of interleukin 2 by peripheral blood and cerebrospinal fluid lymphocytes of patients with multiple sclerosis.

In an effort to further characterize the defective proliferative response of T lymphocytes to mitogens in multiple sclerosis (MS) patients, we examined the response to and production of interleukin 2 (IL 2) by both peripheral blood lymphocytes (PBL) and cerebrospinal fluid mononuclear cells. We also examined the proportion of cells bearing receptors for IL 2 and transferrin. Chronic progressive MS patients have an abnormally low response to exogenous IL 2 as compared to controls. Whereas acute relapse patients' PBL demonstrated a normal IL 2 response during an exacerbation, they showed reduced responsiveness during remission. These abnormalities could not be explained by different dose or kinetic response optima to PHA or IL 2, nor could they be explained by depressed numbers of IL 2 or transferrin receptor-bearing lymphocytes. Production of IL 2 by PBL was also abnormal in MS patients. Chronic progressive patients produced elevated levels of IL 2, whereas acute relapse patients undergoing an exacerbation produced diminished levels of IL 2. During remission, these levels returned to that of controls'. The effect of 1200 rad x-irradiation or nylon wool removal of adherent cells was a significantly greater augmentation of IL 2 production in MS patients than in other neurologic disease or normal controls. Cerebrospinal fluid lymphocytes from MS patients had normal proportions of IL 2 receptor-bearing cells, but were deficient in their IL 2 response and production as compared to autochthonous or control PBL. The inability of some MS patients' lymphocytes to clonally expand in response to IL 2 might contribute to the pathogenicity of the disease.

Cell Separation↗
PubMed1983

Regulation of natural killer cell cytotoxicity by prostaglandin E in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. Part 1. Association between amount of prostaglandin produced, natural killer, and endogenous interferon.

MS patients' peripheral blood mononuclear cells (MNC) spontaneously produced more prostaglandin E1&2 (PGE) in vitro than did OND or normal control MNC correlating with lower levels of NK activity and endogenous interferon (IFN) production while there were no differences between OND and normal controls. MS neat CSF contained significantly higher levels of measurable PGE with concomitantly lower NK activity and % IFN-positive cells than was seen in OND CSF. The PGE producing cells were depleted in the nylon wool-passed (NWP) and enriched in the nylon wool-adherent (NWAd) populations in direct correlation with depletion and enrichment of esterase-positive monocyte/macrophages, respectively, suggesting that at least some of the PGE-producing cells were adherent monocyte/macrophages. At 24 and 48 h after stimulation with PHA, MS unfractionated MNC produced significantly more PGE than OND and normal MNC; at 24 and 72 h, MS NWAd cells produced significantly more PGE than normals and ONDs. MS and ONDs produced the same amount of PGE at 48 h in the stimulated NWAd fraction.

Humans↗
PubMed1983

Regulation of natural killer cell cytotoxicity by prostaglandin E in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. Part 2. Effect of exogenous PGE1 on spontaneous and interferon-induced natural killer.

Compared to normal and other neurological disease (OND) controls, multiple sclerosis (MS) pre nylon wool (pre NW) and nylon wool passed (NWP)-peripheral blood cells' natural killer (NK) activity was more sensitive to prostaglandin E (PGE1); it was suppressed to a greater degree and at lower concentrations of PGE1. At the single cell level this was reflected by lower numbers of target-binding cells (TBCs) and fewer killers among the TBCs. ONDs and normal controls were equally sensitive to PGE1. Though PGE-producing cells were depleted in the NWP population of normal and control ONDs, MS patients still had indomethacin-sensitive NK suppressors in the NWP population; these apparently did not suppress at the single cell effector level but at the level of recycling. MS and OND cerebrospinal fluid (CSF) cells' NK activity could not be 'enhanced' by indomethacin. Depression of interferon (IFN)-induced NK by PGE1 was greater in MS than in OND or normal controls perhaps through its effect on IFN-induced recycling. All subjects' cells maintained sensitivity to PGE1 after overnight incubation in the presence of PGE-producing cells (pre NW) or exogenous PGE1. In sharp contrast to normal and OND controls, MS NWP cells were still inhibited by PGE1 even after overnight incubation in the absence of PGE1.

Alprostadil↗