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Biomedical subjects

M E Westarp

Publications and source records attributed to M E Westarp.

13 recordsLinked to original sources
PubMed1992

Cerebrospinal fluid pheresis in Guillain Barré syndrome.

While plasmapheresis is established in the treatment of acute polyneuroradiculitis, disabling pareses may last long, persisting neurological deficits remain frequent, and costs and side-effects are considerable. Repeated filtration of cerebrospinal fluid may remove pathogenetically relevant cells and polypeptides. Observations in 12 severe Guillain-Barré patients treated with CSF pheresis indicate that it is a safe and effective procedure. We hypothesize mechanisms of action of and potential indications for CSF pheresis as a more general concept. In inflammatory demyelinating polyneuropathy, CSF filtration could be combined with 'dynamic' cerebrospinal fluid pheresis, intravenous immunoglobulin therapy, cryoprecipitation, and/or immuno-adsorption to increase its effectiveness.

Adult↗
PubMed1992

Diagnosis and treatment in a case of juvenile subacute necrotizing encephalopathy Leigh without cytochrome c oxidase deficiency.

Subacute necrotizing encephalopathy (Leigh syndrome) is characterized by lactacidosis, seizures, ataxia, multiple cerebral hypervascularized lesions and mitochondrial oxidation defects. This is a report on a 21-year-old patient with proven Leigh syndrome, mild central and provokable peripheral lactacidosis, an extra-erythrocyte complex II defect, functionally reduced myokinase adenylate deaminase activity, but no ultrastructural mitochondrial changes. Determination of lactate, pyruvate and ammonia under ischemic conditions plus a pyruvate loading test were particularly useful. Oral flunarizine (Sibelium 30 mg/d) proved to be therapeutically effective.

Biopsy↗
PubMed1992

Dermal, serological and CSF changes in amyotrophic lateral sclerosis with and without intrathecal interferon beta treatment.

In 12 patients with amyotrophic lateral sclerosis (ALS) participating in a therapeutic trial with intrathecally applied human fibroblast interferon-beta (IFN-beta) and in 9 untreated ALS patients, we found significantly elevated circulating serum IgG immune complexes (CIC), quantitative immunoglobulin changes, and creatine kinase (CK) elevation; CK reached significantly more often pathological levels in non-bulbar disease. Dermal ultrastructural changes were equally present in all treated as well as untreated ALS patients. Some time ago IL-6 was quantitatively cleaned out of the Fiblaferon-preparation. Erythrocyte sedimentation rate (ESR) rose during intrathecal IFN therapy in 9/10 ALS patients. In 4/4 adequately monitored motoneuron patients, this elevation coincided with a decrease of serum CK, while ESR and CK did not correlate in 60 non-ALS non-IFN neurological controls. Collagen ultrastructure, CSF total protein or barrier function, immune complexes, immunoglobulin quantitation and serum CK may contribute to differentiated diagnosis and should be included in future study protocols.

Adolescent↗
PubMed1991

Hypogammaglobulinemia in McArdle myopathy (glycogenosis type V).

Glycogenosis type V (McArdle) was the first myopathy to be enzymatically defined myopathy and has been found in approximately 120 patients. It is characterized by a myophosphorylase defect. In 2 patients with completely missing phosphorylase activity, muscle fiber necrosis and creatinine kinase elevation, we found reproducibly low gammaglobulins and low immunoglobulin-G. Compared with 124 nonmyopathic control patients with hypogammaglobulinemia, we did not find any established cause for low gammaglobulins in either case of McArdle disease. Myopathies with selected laboratory features or histopathology in common did not show changes in gammaglobulins or immunoglobulins. Unaffected family members had normal gamma-globulins and immunoglobulins. Therefore, gammaglobulins indicate an immunologic involvement in phosphorylase deficiency, and a potential for genomic co-localization.

Adult↗
PubMed1991

Less drug fever with intrathecally applied interferon-beta (short communication).

Systemic therapy of encephalitis with human interferon-beta regularly causes fever up to more than 41 degrees C. Patients often developed hematological changes, nausea and tachycardia. Analyzing the temperature curves of 13 patients with repeated intrathecal, lumbar instillations of 1.0 x 10(6) IU natural IFN-beta, we found markedly less drug-associated fever. Mean temperature was maximal at 38.7 degrees C 12 h after instillation; individual temperature did not exceed 39.7 degrees C, and was elevated for less than 36 h. Day-time of application did not change these results. After the first IFN-beta instillations, the mean integral of temperature vs time was twice as high as after subsequent applications. One and a half days after intrathecal administration and from 39 degrees C on, fever is independent from lumbar IFN-beta. Lower dosage, a more than ten-fold reduction of costs and less interference led us to prefer intrathecal interferon-beta applications. Given the data presented, we cannot yet evaluate clinical efficacy of intrathecal IFN-beta.

Adolescent↗
PubMed1990

Selection of brain choline acetyltransferase synthetic peptides.

Choline acetyltransferase (ChAT) of pig brain is a 640 amino acid enzyme. The sequence has recently been published (Berrard et al., 1988). We identified potentially antigenic epitopes on porcine ChAT by primary and secondary structure analysis. We used 12 structural parameters derived from the amino acid sequence, especially surface antigenicity, internal repetitions and protease cleavage site clusters and superposed gliding averages for the complete ChAT protein. Four peptides from 13 to 21 amino acids in length were defined for antibody production. In detail, we describe a nine-step selection process and discuss costs of synthesis and purification.

Amino Acid Sequence↗
PubMed1990

[Mercaptopurine and silylated mercaptopurine the treatment of experimental allergic encephalomyelitis].

The therapeutic effects of mercaptopurine (6-mercaptopurine, 6-MP) and a silylated derivative (6-trimethylsilylthio-9-trimethyl-silylpurine, S-MP) were compared on the course of T lymphocyte line mediated experimental allergic encephalomyelitis (t-EAE). This transferred EAE is a passively induced model disease in Lewis rats easy to elicit, reliably reproducible and characterized by a dose-dependent lethality. If given at different points in single injections the silicon derivative is shown to be more efficient than 6-MP (43/125 surviving animals compared to 26/129), severity of disease is attenuated and number of survivors increased. Silylation is able to improve blood-brain barrier and cellular permeability; S-MP suppresses intrathecal inflammatory cells more effectively than the original immunosuppressant.

Animals↗
PubMed1987

T lymphocyte line-mediated experimental allergic encephalomyelitis--a pharmacologic model for testing of immunosuppressive agents for the treatment of autoimmune central nervous system disease.

An acute form of transferred experimental allergic encephalomyelitis was induced by injection of activated, myelin basic protein-specific T cell line lymphocytes. The course of the disease as a function of the dose of cytotoxic cells was investigated, and the effect of i.p. and i.v. application of methotrexate on mortality and morbidity was determined. Depending on the time of administration, beneficial therapeutic effects could be seen as early as 1 week. Survival of animals that had received a lethal dose of 15 to 20 X 10(6) cells/kg proved to be the most valuable parameter. T lymphocyte line-mediated experimental allergic encephalomyelitis is a predictable acute central nervous system model disease that does not require antigen depots or cell donor animals.

Animals↗
PubMedDate not supplied

The effect of silyl substituted methotrexate in the treatment of experimental allergic encephalomyelitis in rats mediated by T-line cells.

The effect of methotrexate and of silyl-methotrexate were compared in the treatment of experimental allergic encephalomyelitis (EAE) mediated by T-line lymphocytes. It was demonstrated that, during the first three days after cell transfer, no difference between methotrexate and its silyl derivative could be seen. At a time when the cytotoxic lymphoblasts must have penetrated the blood brain barrier, only silyl methotrexate was able to prevent severe paralysis and death of the animals. It is suggested that the effect of N,N,O,O-Tetrakis (t-butyldimethylsilyl)-methotrexate, (N-4-N-(2,3-bis-t-butyldimethylsilyl-amino-6-pteridinyl-methyl)- methylamino-benzoyl-glutamic acid-bis-(t-butyldimethylsilyl)-ester), depends on the increased lipid solubility and permeability of the blood brain barrier of silylated drugs.

Animals↗