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Biomedical subjects

M E Westarp

Publications and source records attributed to M E Westarp.

At least 19 recordsLinked to original sources
PubMed2000

Medical rehabilitation of chronic progressive disseminated encephalomyelitis (MS).

Eight years after diagnosis, 40% of MS patients develop a chronically progressive form. Annually we treat approximately 200 patients with progressive MS. Treatment consists of medication, i.e. agents that help to prevent future impairment, or interferon-beta injections, and intervals of mitoxantrone infusions (Novantrone(R)), and in some cases cyclic cyclophosphamide (Endoxan(R)) or nucleoside analogue cladribin (Leustatin(R)). Without clear scientific evidence, we recommend unsaturated fatty acids (thistle or sunflower oil), sufficient protein, and freshly prepared fruits and vegetables as a sound basis for remyelination. Remyelination profits from general prophylaxis in the use of ascorbic acid to help prevent urinary infections via acidification, autogenic training to reduce fatigue, improve ventilation of deeper airways, and stimulate vagotonic regeneration, and prevention of unnecessary immune stimulation caused by insects and some food. We recommend the use of sun hats and disencourage blood donation (Allain 1998). Physiotherapy can improve strength, reduce spasticity, and train the patient to compensate for dysbalance and ataxia; supported by beta blockers and good antispastics, tremor and gait disturbances can be positively influenced. Music and motion, speech therapy, realistic training of daily activities, and prudent psychotherapy complete the range of measurements to reconstitute as much as possible of the patient's individual freedom. In the individual, we eventually provide prudent technical aids and careful prognostic estimations. Cooperating with local and regional patient networks, we reinforce long-term disease management and spread up-to-date medical research results, and finally gather valuable contextual information and clinical data on an increasingly frequent idiopathic disease of the human central nervous system.

Adult↗
PubMed1995

HTLV tax-rex DNA and antibodies in idiopathic amyotrophic lateral sclerosis.

In an attempt to verify the possible role of retrovirus in idiopathic amyotrophic lateral sclerosis (ALS), the sera of 21 ALS patients admitted to the Neurological Unit of the Don Gnocchi Foundation in Milan, Italy, and of 9 ALS patients from Ulm University in Germany have been evaluated for the presence of antibodies to the human T-lymphotropic viruses (HTLV-I and HTLV-II). The sera of 30 healthy individuals and 20 HIV-infected but HTLV-negative subjects have been also studied as control. Moreover, the HTLV tax-rex and pol DNA sequence have been searched in the peripheral blood mononuclear cells (PBMCs) of 15 ALS patients and 15 HIV-positive HTLV-negative subjects using a nested PCR currently employed in our laboratory for the study of HTLV infections. Antibodies to one or more HTLV proteins have been found by using a Western blot (WB) kit in the sera of 10 Italian and 7 German ALS cases, while all the healthy controls were negative and only one HIV-positive subject had antibodies to HTLV gp21. HTLV tax-rex sequences have been found in the PBMCs of 6 ALS patients while all the controls were negative. All 15 ALS cases and controls were negative for HTLV pol DNA indicating that only the most conserved region of the HTLV genome could be detected. On the whole our data indicate that some ALS patients have antibodies to HTLV proteins and that the tax-rex region of the HTLV genome can be found in their PBMCs.

Adult↗
PubMed1995

Sporadic ALS/MND: a global neurodegeneration with retroviral involvement?

Sporadic amyotrophic lateral sclerosis may be an aetiologically heterogenous disease. We confirmed elevated circulating IgG immune complexes, and altered IgG seroreactivities against human retroviral antigens (HIV-2 and HTLV immunoblots) in overlapping subgroups of patients. Together with preliminary findings of a positive polymerase chain reactivity for human T-lymphotropic virus (HTLV.tax/rex) in blood leukocytes of 5 out of 14 sALS patients, we interpret this as evidence for a retroviral involvement in this relentlessly progressive, often asymmetrically spreading neurodegeneration. The possibility of a secondary phenomenon seems unlikely, yet cannot be completely ruled out.

Adult↗
PubMed1994

Immunoglobulin-G isotype changes in human sporadic amyotrophic lateral sclerosis (ALS).

Out of 50 patients with sporadic amyotrophic lateral sclerosis (sALS), excluding 8 patients with recent immunosuppressive medication or low total IgG, we examined all available 92 sera of 11 women and 31 men nephelometrically for serum immunoglobulin concentrations including IgG isotypes IgG1-4. Mean serum levels of IgA and IgM remained within references in all cases. Isotypes IgG1 and IgG3 were the most frequently altered immunoglobulins. Without specific treatment, 34 out of 42 patients (= 80%) and 58 out of 92 sera (= 63%) demonstrated low IgG3 concentrations (< 0.41 g/l), while 14 patients (= 33%) and 20 sera (= 22%) demonstrated low IgG1 serum levels (< 4.22 g/l). In patients with normal total IgG, isotypes IgG1 and IgG2 often changed in a complementary way, and IgG1/IgG2 serum concentrations correlated significantly (rs = -0.518, P < 0.001). In four longitudinally monitored patients, the IgG3 isotype ranged from 1.3% to 8.2% of serum IgG and demonstrated a remarkable individual variability over time, corresponding to the relatively short half-life of IgG3. Since elevated circulating immune complexes may fluctuate rapidly, altered serum immunoglobulin isotypes could become more convenient parameters in a still enigmatic disease. To assess their role and relevance, their association with clinical course, cerebrospinal fluid and circulating immune complexes has to be examined.

Adolescent↗
PubMed1994

Retroviral synthetic peptide serum antibodies in human sporadic amyotrophic lateral sclerosis.

We examined 101 sera from 32 adult sporadic amyotrophic lateral sclerosis (ALS) patients, including nine with positive enzyme-linked immunosorbent assay (ELISA) serum antibodies against human spuma retrovirus (HSRV) [human foamy virus (HFV)] envelope (env) and/or capsid (gag) proteins, for peptide seroreactivity. Synthetic peptides 10 to 14 amino acids in length were selected from HSRV (3), maedi-visna virus (1), human nerve growth factor-beta (1), and human amyloid-beta sequences (1). Eighteen of 101 ALS sera compared with six of 144 control sera reacted to any of the sequences (p < 0.01) (i.e., 8/32 ALS patients and 2/93 control patients bound to a synthetic peptide, p < 0.01). Peptide VLA- [NGF beta(1-14)] was reproducibly recognized by one of the 93 neurologic controls, and one of the 32 ALS patients reproducibly reacted to synthetic peptides [EET-, HSRVenv/NGF beta(55-61)] and [GSN-, beta-amyloid(25-35)] simultaneously. This amyloid-A(25-35) peptide corresponds to the neurotoxic and neurotrophic tachykinin homology sequence described by Yanker. Only ALS patients (no controls) reacted with the visna/CNTF peptide SMC- and HSRVbcl-1/amyloid(740-751) peptide EGP-. Testing a total of 245 sera from 125 patients, three reproducible reactivities (two ALS, one OND) were observed both with and without glutaraldehyde linkage. Of the four peptides recognized either by more than one serum from the same patient with ALS or by sera from ALS patients only (EET-, GSN-, SMC-, EGP-), two share a circumscript homology with maedi-visna virus envelope glycoprotein (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Improving medical approaches to primary CNS malignancies--retinoid therapy and more.

Successfully inducing differentiation in ectodermal diseases, retinoids harbour considerable therapeutic potential in the treatment of neuroectodermal-neuroepithelial malignancies. The principal tissue retinoid, retinoic acid, can be potently upregulated in vivo by a relatively specific catabolic inhibitor, R75251 (liarozole). Both substances have been given orally over 2 years in addition to standard treatment, and have been well tolerated. Corresponding closely to plasma retinoid levels, cutaneous side effects facilitate individual dosing. We evaluate this adjuvant retinoid approach and additional efforts to improve therapy of primary CNS malignancies, including the topical administration of retinoids in gamma linolenic acid.

Aged↗
PubMed1993

Antiretroviral therapy in sporadic adult amyotrophic lateral sclerosis.

Clinical and experimental findings in idiopathic amyothrophic lateral sclerosis (ALS) would be compatible with a retroviral involvement. In 35 adult patients with non-familial ALS we observed elevated circulating immune complexes, a decrease in IgG3 isotype and enzyme-linked sorbent assay (ELISA) serum antibodies against human spuma retrovirus (HSRV), confirmed by specific human foamy virus immunoblots. All 35 were negative for IgM or relevant IgG anti-ganglioside antibodies. We treated 12 HIV-negative, immune-complex-positive ALS patients with 500 mg d-1 zidovudine p.o. over 2-10 months and found reductions of serum creatine kinase and circulating immune complexes from two days to two weeks after the beginning of medication.

Adult↗
PubMed1993

Antibodies raised against synthetic peptides react with choline acetyltransferase in various immunoassays and in immunohistochemistry.

Antisera were raised in rabbits against five synthetic peptides. These peptides have been identified as potentially antigenic epitopes from the sequence of porcine choline acetyltransferase (ChAT) using primary and secondary structure analysis. All five antisera recognized immunoaffinity-purified antigen from porcine brain in an ELISA and on western blots. Four antisera recognized ChAT on dot blots, and another four antisera reacted with native and degraded enzyme in a sandwich ELISA using monoclonal antibodies as the capture antibody. One peptide antiserum was of similar avidity in this sandwich ELISA as a polyclonal antibody raised against immunoaffinity-purified ChAT. The same antiserum reacted with the enzyme from human placenta in an ELISA and on western and dot blots and recognized ChAT in rat, primate, and human neurons. Thus, a single peptide (amino acids 168-189) provides the means for easy, reliable, and reproducible generation of antibodies against ChAT suitable for replacing conventional polyclonal and monoclonal antibodies.

Animals↗
PubMed1993

[Amyotrophic lateral sclerosis--indications of increased antiretroviral seroreactivity without obvious epidemiology].

Of 25 male and 13 female patients diagnosed as sporadic cases of amyotrophic lateral sclerosis between 1989 and 1992, 17 had reproducible serum antibodies against human foamy virus (HFV = human spuma retrovirus, HSRV). HFV-positive ALS patients had higher IgG3 concentrations than HFV-negatives (P < 0.05) and competed better on maedi-visna retroviral antigen than HFV-negatives or controls (P < 0.05), but did not differ otherwise. Two HFV-positive patients were living in the same building; two other ALS patients lived within 300 m of one another, and three HFV gag reactive men (2 ALS, 1 control) were living in neighbouring villages. These were the closest geographic clusters found among current patients. We summarize recent findings compatible with a pathogenetic role for endogenous and/or exogenous retroviral sequences in adult motor neuron disease, and confirm a male preponderance as well as an inverse correlation between survival time and age at onset.

Adult↗
PubMed1993

Retroviral interference with neuronotrophic signaling in human motor neuron disease?

We tested 13/32 patients with non-familial amyotrophic lateral sclerosis (ALS) positive (41%) for human spuma retrovirus (HSRV) seroreactivity. Half the non-ALS HSRV-positive neurologic patients (12/25) reported multiple fasciculations within the last two years. Sera from four HSRV-env negative ALS patients measurably competed with visna antibodies on maedi-visna antigen. The serologies for bovine leukemia virus, Borna disease virus and GM1IgM-antibodies remained negative. Both visna and foamy virus sequences share epitopes with motor nervous system signal polypeptides, suggesting a retroviral interference with motor neurono-axonal function and neuronotrophic signals.

Adolescent↗
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↗