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Biomedical subjects

L W Myers

Publications and source records attributed to L W Myers.

At least 19 recordsLinked to original sources
PubMed1991

Preferential reductions in lymphocyte sub-populations induced by monthly pulses of chlorambucil: studies in patients with chronic progressive multiple sclerosis.

Thirty-three patients with chronic progressive multiple sclerosis (MS) were assigned to intervention groups receiving monthly pulses of chlorambucil (CB) for about one year. The monthly doses ranged from 0.4 to 1.5 mg/kg. Administration of CB resulted in preferential reduction in different lymphocyte subsets which was dose- and time-dependent. The number of B-cells (CD20) decreased more rapidly than NK-cells (CD16, CD56, CD16+CD56+) or T-cell (CD3) and T-cells subsets (CD4 and CD8). At 1.2 mg/kg, CB administration resulted in a preferential drop of T-suppressor/cytotoxic cells (CD8) compared with T-helper cells (CD4), and of the less mature "virgin" CD4 cells (CD4+CD45RA+) compared with "memory" CD4 cells (CD4+CD45RA-). The expression of activation markers (transferrin receptor, CALLa, HLA-Dr and CD38[OKT10]) within CD4, CD8 or CD20 lymphocytes was not altered by CB administration. Our data, which show that CB administration results in a preferential fall in B-cell numbers, contrast with the effects of long-term administration of the related immunosuppressive drugs, azathioprine and cyclophosphamide.

Antigens, CD↗
PubMed1990

Failure to detect human T-cell leukemia virus-related sequences in multiple sclerosis blood.

We tested 11 patients with multiple sclerosis for the presence of human T-cell leukemia virus type I (HTLV-I)- or type II (HTLV-II)-related sequences. DNA from blood mononuclear cells was analyzed by the polymerase chain reaction utilizing three different oligonucleotide primer pairs. Two of these primer pairs detect sequences shared between HTLV-I and HTLV-II in either p24, gag protein, or in p21, env transmembrane protein. The third primer pair was synthesized based on regions in the pol gene where amino acid sequences are conserved between HTLV-I, HTLV-II, and the related bovine leukemia virus. The multiple sclerosis samples were consistently negative while appropriate control samples were positive. We conclude that viruses related to HTLV-I, HTLV-II, or bovine leukemia virus are not present in the blood of patients with multiple sclerosis and, therefore, that HTLV-bovine leukemia virus-related viruses are not likely to be involved in the pathogenesis of multiple sclerosis.

Amino Acid Sequence↗
PubMed1990

The peculiar difficulties of therapeutic trials for multiple sclerosis.

Because the immune response appears important in the pathogenesis of MS, anti-inflammatory and immunomodulatory drugs and agents are used as a palliative treatment. Azathioprine alone is minimally efficacious and probably not worth the bother and risk. Cyclophosphamide alone is too toxic. Although cyclosporine A may slow the rate of deterioration in chronic progressive MS, adverse effects may limit its use outside major centers. Gamma interferon provokes exacerbations and should not be used. We do not recommend copolymer-1, alpha or beta interferon, monoclonal antibodies, plasmapheresis, and total lymphoid irradiation except in well-designed experimental protocols. Combination therapy of adrenal cortical steroids (ACS) with other immunosuppressants (cyclophosphamide or cyclosporine) merits further study. We think "pulse" synthetic ACS therapy has advantages over corticotropin and will become the "standard of care" for exacerbations. We also would try it for chronic progression. Even then, with the pulse treatment we still must determine the optimum dose, route, duration, and need for "taper."

Adrenocorticotropic Hormone↗
PubMed1989

In vitro study of mediators of inflammation in multiple sclerosis.

Prostaglandin E levels have previously been demonstrated to be elevated in multiple sclerosis (MS). We have further investigated other products of activated macrophages related to inflammation. We report here on prostaglandin E and its relationship to interleukin 1, tumor necrosis factor, and leukotriene B4 produced by macrophages from blood and cerebrospinal fluid of MS patients and controls in vitro. Interleukin and tumor necrosis factor are elevated significantly after stimulation in MS, while leukotriene B4 production by blood macrophages is depressed compared to other neurological disease and normal healthy controls. In 40% of MS patients tested, peripheral blood macrophages spontaneously produced elevated levels of interleukin 1. All mediators of inflammation are produced in increased amounts by MS cerebrospinal fluid leukocytes after stimulation. Macrophages from MS blood are not as sensitive as controls to nonsteroidal inhibitors specific for lipoxygenase or cyclo-oxygenase pathways. Positive correlations of elevations in production of such mediators of inflammation as prostaglandin E, interleukin 1, and tumor necrosis factor in MS were significant. Elevated production of these mediators in combination with insensitivity to inhibitors of inflammation suggests a role for activated macrophages in the demyelination process.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis.

Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose "pulse" and alternate-day regimen. The "intent-to-treat" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS.

Adolescent↗
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

Quantitation of myelination and demyelination by the measurement of myelin basic protein by ELISA.

Utilizing a competitive inhibition enzyme-linked immunosorbent assay (ELISA) we measured the amount of myelin basic protein (MBP) in brain, liver, and kidney of newborn mouse and compared these values with myelinated cerebellar explant cultures under various conditions. Explant cultures demyelinated with anti-myelin serum showed a 90% decrease in MBP when compared with controls. These results correlated with myelination and demyelination as observed by light microscopy. Newborn tissues including brain showed only negligible activity for MBP. This technique provides a sensitive and objective method for quantitating in-vitro demyelination.

Animals↗
PubMed1979

HLA types and immunity in multiple sclerosis.

HLA types and levels of humoral and cell-mediated immune responses to several antigens were studied in a large group of patients with multiple sclerosis, and in controls. Patients were more likely than controls to have the DRw2 antigen. They had higher mean antibody titers to measles but not to cytomegalovirus, herpes 1, or herpes 2, and had less competent cell-mediated responses. Antibody titers to measles were lower and cell-mediated immune responses were more effective in patients with the DRw2 antigen in patients than in patients without it. This apparent specificity for measles suggests that the etiology of multiple sclerosis is related to the immune response to measles or related viruses.

Antibodies, Viral↗
PubMed1977

Histocompatibility types and measles antibodies in multiple sclerosis.

The relationship between HLA antigens and measles antibody titers was investigated in 105 multiple sclerosis (MS) patients. HLA antigens were determined serologically by a micro-lymphocytotoxicity test and measles antibody titers were determined by the hemagglutination inhibition test. There was an increased frequency of HLA-B7 and HLA-Bw35 antigens and a decreased frequency of HLA-A2, HLA-B12, and HLA-Bw40 antigens in MS. Measles antibody titers were significantly higher in MS than in control cases. In the MS patients, the chi-square test for homogeneity did not show any significant difference between the presence or absence of antigens HLA-A3, HLA-B7, HLA-B8 HLA-A2 or HLA-B12 when compared with measles antibody titers. The chi-square test for association did not show any significant difference between the presence or absence of these antigens compared with measles antibody titers above 1:64 or 1:128 or 1:256. However, there were significantly higher measles antibody geometric mean titers in MS patients with HLA-A3 antigen or lacking HLA-A2 antigen. In the case of HLA-A3, this was reflected in the female but not in the male patients. The increased measles HI antibody titer in MS may be related to the increased frequency of HLA-A3, or the decreased frequency of HLA-A2, or both.

Antibodies, Viral↗
PubMed1977

Swine influenza virus vaccination in patients with multiple sclerosis.

A double-blind, placebo-controlled study was conducted to evaluate the safety and efficacy of inactivated influenza virus vaccines in patients with multiple sclerosis. The vaccine used contained 200 chick cell-agglutinating (CCA) units of influenza A/New Jersey/76 and 200 CCA units of influenza A/Victoria/75 whole viruses (Merrell-National Laboratories, Cincinnati, Ohio). The frequency of clinical relapses of multiple sclerosis was the same in the vaccine-treated (four of 33 patients) and placebo-treated (four of 33) groups. An untreated control group had a slightly higher rate of relapses (four of 22). Toxic reactions to the vaccine were not a significant problem. The efficacy of the vaccination as measured by titers of hemagglutination-inhibiting antibody was comparable to that reported for the general population. However, patients with preexisting antibody were less responsive to the vaccine than normal controls studied previously. The patients who did not respond to the vaccine tended to be older and more disabled. There were no changes in titers of antibody to rubeola or rubella virus after vaccination or in relation to change in clinical course. It is concluded that the vaccine is safe and effective in patients with multiple sclerosis.

Antibodies, Viral↗