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Biomedical subjects

Uwe K Zettl

Publications and source records attributed to Uwe K Zettl.

18 recordsLinked to original sources
PubMed2006

Frequency of current utilisation of complementary and alternative medicine by patients with multiple sclerosis.

OBJECTIVE: The purpose of the study was to examine the frequency and characteristics of complementary and alternative medicine (CAM) use among patients with multiple sclerosis (MS). METHOD: In order to collect sociodemographic and disease related variables as well as aspects of CAM utilisation 254 MS patients were examined with an interview. The investigation was completed by data of the neurological examination. RESULTS: At the time of investigation 67.3% of the MS patients reported that they were currently using one or more CAMs. Overall, most of the overall utilized therapies (90.6%) were chosen as a complement and 9.4% as an alternative therapy. Users of complementary medicine were more severely affected by the MS than non-users and had a longer duration of illness. No sociodemographic differences were found between users and non-users. When evaluating the efficacy of CAM, patients reported improvement in 67.1%, no influence in 32.3% and worsening in 0.6% of the cases. 3.7% of the CAM therapies were accompanied by minor side effects. CONCLUSIONS: Since MS patients are frequently using CAM despite the absence of clinically proven efficacy and appraise it positively, further research on the motivation for utilisation and on objective effects of CAM are needed.

Adult↗
PubMed2006

Intravenous immunoglobulins as therapeutic option in the treatment of multiple sclerosis.

Treatment of neurological disorders with intravenous immunoglobulin (IVIG) is an increasing feature of practice for an expanding range of indications. This article reviews the current literature regarding the role of IVIG treatment in multiple sclerosis (MS) and summarizes recommendations for the use of IVIG in different courses and clinical subsets of the disease. Principally based on the results of four randomized, double-blind, placebo-controlled trials (RCTs) and a corresponding meta-analysis, the amount of evidence for the efficacy of IVIG treatment is currently most convincing for the relapsing-remitting course of MS (RRMS); nevertheless, it lags clearly behind that for beta interferon due to smaller study sizes, partial deficits in study design and not established optimal dosage. This prompted the basis for a consensus statement in some countries to recommend IVIG as second-line treatment in RRMS, when other licensed therapies (i. e., beta interferon, glatiramer acetate) are individually not tolerated due to side effects or concomitant disease. Recent evidence indicates that IVIG is also effective in clinically isolated syndrome (CIS) and should be considered as a therapeutic option, particularly when licensed immunotherapy can not be offered. During an acute relapse additional IVIG administration to established steroid treatment showed no benefit. Despite promising experimental data on promotion of remyelination, fixed chronic deficits were not reversed or improved by long-term IVIG treatment either. Currently there is no indication for IVIG treatment in the chronic progressive disease stages, since a large and well-designed RCT failed to show any beneficial effect in patients with secondary progressive MS (SPMS) and data derived from primary progressive MS (PPMS) are still pending. However, preliminary results of a so far unpublished RCT including patients with PPMS and SPMS suggest a strong trend towards a beneficial effect in PPMS. So far, IVIG is the only therapy investigated for reducing postpartum relapses, whereas immunomodulatory drugs are contraindicated during pregnancy and lactation period. Data evaluating the peripartal use of IVIG along with the positive results of the trials in RRMS justify postpartal IVIG treatment particularly for mothers, who choose to breastfeed, under consideration of the recommendations specified for the relapsing-remitting disease course. As recently shown IVIG administration right from the early weeks of pregnancy appears to be a promising strategy, but cannot be recommended from the viewpoint of evidence-based medicine.

Female↗
PubMed2006

Intravenous immunoglobulin therapy in neurological diseases during pregnancy.

Immunological changes during pregnancy influence the course of neurological autoimmune diseases in different ways. In case of pregnancy immunomodulatory standard therapies such as interferon-beta, glatiramer acetate,monoclonal antibodies and cytostatics mostly should be discontinued. In those cases intravenous immunoglobulin (IVIg) therapy might be an alternative. In some diseases, contemporary publications describe positive therapeutic effects on the course of disease during or after pregnancy.

Autoimmune Diseases of the Nervous System↗
PubMed2006

Adverse effects of treatment with intravenous immunoglobulins for neurological diseases.

Therapy with intravenous immunoglobulins (IVIg) is considered to be a safe treatment for a number of immune-mediated neurological diseases. Published data about prevalence of adverse effects range from 11 to 81%. The purpose of our study was to preserve a representative view on adverse effects by analysis of a large cohort of patients treated by IVIg. A recent prospective study reported 42.7% adverse events. The majority of patients presented with minor adverse effects, mostly asymptomatic laboratory changes. Rash or mild headache occurred especially when IVIg was administered with an infusion flow higher than 10 g/h. Severe complications like deep vein thrombosis or others are rare. In addition to its efficacy, IVIg therapy appears to be a safe therapy in immune-mediated neurological diseases. Most patients show no or minor adverse effects. Patients with pre-existent disorders like heart or renal insufficiency or immobilized patients, however, may be at higher risk for complications.

Contraindications↗
PubMed2006

Multiple sclerosis therapy monitoring based on gene expression.

Multiple sclerosis (MS) is the most prevalent chronic autoimmune, neurodegenerative disorder of the central nervous system (CNS). Despite substantial progress, treatment of MS and other autoimmune diseases is only moderately effective. It is anticipated that the treatment of autoimmune diseases with single drugs or biological approaches will in the future be complemented, or even replaced, by combination therapies, which include immunomodulation, elimination of infectious triggers and tissue repair. One proclaimed goal of biomedical research and clinical practice is the discovery of sets of genes with expression that correlates with successful outcomes of drug therapy, or with unfortunate side effects. Such information has direct consequences for selection, refinement or development of treatments and will soon be translated into clinical trials. The genome-wide RNA profile of an individual represents one complement to the comprehensive determination of disease- or drug response-related elements; comparable to a 'sentinel' method, it serves as a large-scale approach to MS biology. This work reviews the state of the art in MS research at the transcriptome level applying genomewide screening methods. It discusses implications in understanding disease pathogenicity, diagnostic markers, the identification of new therapeutic targets and a classification of patients towards the advent of tailored therapies.

Biomarkers↗
PubMed2006

Comparative genomics for the investigation of autoimmune diseases.

The complete DNA sequence of the human genome and of several related mammals are now available, due to the investments of enormous resources and advances in sequencing technology. Novel technologies have been developed to compare multiple genomes with each other, thus specifying regions of sequence similarity among mammals and with their pathogens. Larger blocks of sequence similarity (syntenic regions) have been determined and made publicly available. In many ways, novel insights can be gained by such data when combining external genetic or clinical information for these syntenic loci. These novel tools have proven to be successful in inferring functional equivalence between loci of multiple genomes. This review reports on the role of comparative genomics in research on autoimmune diseases, a field with strong dependencies on animal models of human diseases and the problem of an adequate information transfer between multiple organisms and research areas.

Animals↗
PubMed2005

How frequently do patients with multiple sclerosis use complementary and alternative medicine?

OBJECTIVE: The purpose of the study was to examine the prevalence and characteristics of the utilisation of complementary and alternative medicine (CAM) by patients with multiple sclerosis (MS). DESIGN: Cross-sectional study using a semi-structured interview. SETTING: One hundred and fifty-four MS patients were examined by interview to collect sociodemographic and disease-related variables as well as aspects of their usage of CAM. The investigation was completed by data from neurological examination. MAIN OUTCOME MEASURES: Reported utilisation of CAM by MS patients. RESULTS: At the time of the investigation 61.7% (n = 95) of the MS patients reported that they were currently using CAM. Most of the therapies utilised (90.3%; n = 205) were complementary and only 9.7% (n = 22) were alternative choices. Users of complementary medicine were more severely affected by the disease than non-users, but no sociodemographic differences between users and non-users were found. Concerning the efficacy of CAM, 65.8% (n = 146) of MS patients reported improvement, 32.9% (n = 73) no influence, and 1.3% (n = 3) worsening of their condition. 4.5% (n = 10) of the CAM therapies were accompanied by slight side-effects. CONCLUSION: A large proportion of MS patients use unconventional treatments, yet clinical studies on the efficacy of CAM in these cases have not been undertaken. Therefore, further research on their motivation and on objective effects of CAM is required.

Adult↗
PubMed2005

Collection of soluble variants of membrane proteins for transcriptomics and proteomics.

The existence of a soluble splice variant for a gene encoding a transmembrane protein suggests that this gene plays a role in intercellular signalling, particularly in immunological processes. Also, the absence of a splice variant of a reported soluble variant suggests exclusive control of the solubilisation by proteolytic cleavage. Soluble splice variants of membrane proteins may also be interesting targets for crystallisation as their structure may be expected to preserve, at least partially, their function as integral membrane proteins, whose structures are most difficult to determine. This paper presents a dataset derived from the literature in an attempt to collect all reported soluble variants of membrane proteins, be they splice variants or shedded. A list of soluble variants is derived in silico from Ensembl. These are checked on their presence in multiple organisms and their number of membranespanning regions is inspected. The findings then are confirmed by a comparison with identified proteins of a recent global proteomics study of human blood plasma. Finally, a tool to determine novel soluble variants by proteomics is provided.

Animals↗
PubMed2004

In silico fine-mapping: narrowing disease-associated loci by intergenomics.

UNLABELLED: Genetic linkage and association studies define quantitative trait loci (QTLs) and susceptibility loci (SLs) that influence the phenotype of polygenic traits. A web-accessible application was created to identify intergenomic consensuses to fine map QTLs and SLs in silico and select particularly promising candidate genes for such traits. Furthermore, this approach offers an empirical evaluation of animal models for their applicability to the study of human traits. AVAILABILITY: http://qtl.pzr.uni-rostock.de/qtlmix.php CONTACT: serrano@pzr.uni-rostock.de.

Animals↗
PubMed2004

Long-term growth selection of mice changes the intrinsic susceptibility of myogenic cells to apoptosis.

Myogenic cells were derived from mice long-term selected over 70 generations for high 6-weeks body weight (DU-6) and from unselected control mice (DU-Ks). The cells were grown in medium with 10% foetal bovine serum (FBS) for 8 days or transferred to low serum conditions (1% FBS) at days 4 and 6 of cultivation, respectively, and maintained for two further days. In both cell lines, serum reduction induced decreases in DNA and protein contents, and in DNA synthesis rate. It also triggered apoptotic cell death as demonstrated by increased DNA strand breaks and expression of active caspase-3. Concomitantly, the anti-apoptotic protein bcl-2 was enhanced. The basal frequency of apoptotic cells decreased with time of cultivation in both lines and was lower in DU-6 than in DU-Ks cells. However, the increase in apoptosis induced by serum reduction was more pronounced in DU-6 than in DU-Ks cells and did not differ between the time points of serum reduction. The results suggest that growth selection decreases the basal apoptosis frequency of muscle satellite cells under normal supply, but enhances the intrinsic susceptibility to growth factor withdrawal by serum deprivation as a severe apoptotic stimulus. Furthermore, the apoptotic response to growth factor withdrawal seems to be largely independent of the stage of myogenic development.

Animals↗
PubMed2004

Transcription factors in autoimmune diseases.

The analysis of the molecular basis of autoimmune diseases is currently under intense investigation. The identification of novel mechanisms underlying the pathogenesis of these diseases generates the possibility for the development of new therapeutic agents. In this review we summarize the results leading to novel insights concerning the molecular processes involved in the pathogenesis of rheumatoid arthritis, systemic lupus erythematodes, multiple sclerosis and diabetes type 1. We focus on the role of transcription factors such as nuclear factor kappa B, activator protein 1, peroxisome proliferator-activated receptor, vitamin D receptor and the glucocorticoid receptor that mediate pro- and anti-inflammatory effects and therefore represent direct or indirect targets for therapeutic intervention.

Animals↗
PubMed2004

Selecting SNPs for association studies based on population frequencies: a novel interactive tool and its application to polygenic diseases.

Common complex polygenic diseases as autoimmune diseases have not been completely understood on a molecular level. While many genes are known to be involved in the pathways responsible for the phenotype, explicit causes for the susceptibility of the disease remain to be elucidated. The susceptibility to disease is thought to be the result of genetic epistatic interactions between common polymorphic genes. This polymorphism is mostly caused by single nucleotide polymorphisms (SNPs). Human subpopulations are known to differ in the susceptibility to the diseases and generally in the distribution of single nucleotide polymorphisms. The here presented approach retrieves SNPs with the most divergent frequencies for selected human subpopulations to help defining properties for the experimental verification of SNPs within defined regions. A web-accessible program implementing this approach was evaluated for multiple sclerosis (MS), a common human polygenic disease. A link to a summary of data from "The SNP Consortium" (TSC) with sex-dependencies of SNPs is available. Associations of SNPs to genes, genetic markers and chromosomal loci are retrieved from the Ensembl project. This tool is recommended to be used in conjunction with microarray analyses or marker association studies that link genes or chromosomal loci to particular diseases.

Gene Frequency↗
PubMed2003

Susceptibility to apoptosis in different murine muscle cell lines.

Objective of the study was to investigate growth characteristics and susceptibility to apoptosis in different murine muscle cell lines (selected for high body weight, DU-6; randomly mated control, DU-Ks; immortalized myoblast cell line, C2C12). Apoptosis was induced by serum deprivation. At days 4, 5, and 6 of cultivation, protein, DNA and the frequency of apoptotic cells were determined. Until day 4, C2C12 accumulated more DNA and protein compared with DU-Ks and DU-6, while exhibiting a lower percentage of apoptotic cells. Serum deprivation impaired the growth of each cell line. C2C12 continued to accumulate DNA and protein after serum deprivation, whereas reductions, indicative of cell death, were apparent in DU-Ks and DU-6. Serum deprivation did not enhance apoptosis in C2C12. Higher percentages of apoptosis were observed in DU-Ks and DU-6 after 2 days of serum deprivation with greater responsiveness of DU-6 to serum deprivation. The results suggest that cell loss in response to serum deprivation is in part due to induction of apoptosis. C2C12 are less sensitive to sub-optimal culture conditions compared with DU-Ks and DU-6 which are at a closer distance to the in vivo status. Moreover, long-term selection for growth decreases the basic frequency of apoptosis of muscle satellite cells, but increases their susceptibility to apoptosis induction.

Animals↗
PubMed2003

Lymphocyte subpopulations, oxidative burst and apoptosis in peripheral blood cells of patients with multiple sclerosis-effect of interferon-beta.

At present, the most efficient therapeutical treatment of multiple sclerosis (MS) is achieved by IFN-beta. However, its in vivo effects remain incompletely understood. If applied parenterally, the hydrophobic IFN-beta acts primarily on blood cells with probable selectivity for functionally different lymphocyte subpopulations, monocytes and granulocytes. We have investigated the expression of the activation marker interleukin-2 receptor-alpha (CD25) on CD3+ T cells, CD19+ B cells, foetal-type gamma(delta)+CD3+ T cells and foetal-type CD5+CD19+ B cells of the peripheral blood. In addition, the oxidative burst activity and apoptosis have been determined in mononuclear and polymorphonuclear blood cells, respectively. The study accompanied a phase III trial with IFN-beta1b (BETAFERON, Schering). Two groups of MS patients with relapsing-remitting course of the disease have been investigated at 8 time points (days 0, 5, 15, 31, 60, 90, 180 and 270 after starting therapy): (1) verum group (n = 8) with application of 8 Mill. units IFN-beta1 b every other day, and (2) placebo group (n = 4) with application of placebo for 3 months and therapy as in (1) from day 90 onward. The main results were: (1) Activated T cells decreased until day 180 in the verum group and return thereafter to pre-treatment values, whereas in the placebo group the values remained relatively stable over the whole observation period. (2) Activated B cells increased between days 90 and 270 in both groups, i.e. after verum application in both groups. (3) Foetal-type B cells were more activated than total B and T cells with increase over time in both groups. (4) Foetal-type T cells exerted relatively stable intra-individual levels with generally low CD25 expression, but punctual CD25 peaks in both groups. (5) The spontaneous oxidative burst was higher in lymphocytes, more variable in monocytes and faster increasing in granulocytes in the verum group than in the placebo group. (6) Apoptosis of mononuclear cells and granulocytes showed similar variations in the verum and placebo groups with the exception of a selective increase over time of the proportion of granulocytes undergoing induced apoptosis in the verum group. It is concluded that IFN-beta has the following main effects on the immune system of MS patients: (1) the T cell immunity is systemically and reversibly suppressed, (2) the foetal-type lymphocytes, which are responsible for the first line of defence of infections, are stimulated in the long range, (3) the oxidative burst activity is increased in lymphocytes and granulocytes and instable in monocytes, and (4) the inducibility of apoptosis in granulocytes is increased. Re-examination of the altered blood cell parameters after long-term IFN-beta therapy is warranted.

Adult↗
PubMed2003

Therapy with intravenous immunoglobulins: complications and side-effects.

Therapy with intravenous immunoglobulins (IVIG) is thought to be a safe treatment for a number of immune-mediated neurological diseases. Published data about prevalence of adverse effects range from 11 to 81%. The purpose of our study was to present a representative view on adverse effects by analysis of a large cohort of patients treated by IVIG. In a prospective study, we analysed 117 patients (age 17-79 years) who were treated with IVIG for various neurological diseases including chronic inflammatory demyelinating polyneuropathy, diabetic amyotrophy, inclusion body myositis, multiple sclerosis, Guillain-Barré syndrome, Miller-Fisher syndrome, multifocal motor neuropathy, myasthenia gravis and polymyositis. IVIG therapy was applied at a dose of 0.4 g/kg body weight/day in a total of 408 therapy courses. 42.7% showed adverse events. The majority of patients presented with minor adverse effects, mostly asymptomatic laboratory changes. Rash or mild headache occurred in 8 patients, especially when IVIG was given with infusion flow higher than 10 g/h. Two patients showed a severe complication with deep vein thrombosis. In summary, beside its effectiveness in immune mediated neurological diseases, therapy with IVIG seems to be a safe therapy. Most patients show no or minor adverse effects. Patients with pre-existent disorders like heart or renal insufficiency or immobilised patients, however, may be at higher risk for complications.

Adolescent↗