PubMed Health⌕ Search

Biomedical subjects

Hans-Christian von Büdingen

Publications and source records attributed to Hans-Christian von Büdingen.

8 recordsLinked to original sources
PubMed2006

Early recurrent ischemic stroke in stroke patients undergoing intravenous thrombolysis.

BACKGROUND: We assessed the incidence of early recurrent ischemic stroke in stroke patients treated with intravenous tissue-type plasminogen activator (tPA) and the temporal pattern of its occurrence compared with symptomatic intracranial hemorrhage (ICH). METHODS AND RESULTS: Prospectively collected, population-based data for 341 consecutive acute stroke patients (62% men; mean age, 66 years) treated with tPA according to the National Institute of Neurological Disorders and Stroke study protocol at 8 medical centers in Switzerland (3 academic and 5 community) between January 2001 and November 2004 were retrospectively analyzed. The primary outcome measure was neurological deterioration > or = 4 points on the National Institutes of Health Stroke Scale occurring within 24 hours of tPA treatment and caused either by recurrent ischemic stroke (defined as the occurrence of new neurological symptoms suggesting involvement of initially unaffected vascular territories and evidence of corresponding ischemic lesions on cranial computed tomography scans, in the absence of ICH) or by ICH. Early recurrent ischemic stroke was diagnosed in 2 patients (0.59%; 95% confidence interval, 0.07% to 2.10%) and symptomatic ICH in 15 patients (4.40%; 95% confidence interval, 2.48% to 7.15%). Both recurrent ischemic strokes occurred during thrombolysis, whereas symptomatic ICHs occurred 2 to 22 hours after termination of tPA infusion. CONCLUSIONS: Recurrent ischemic stroke is a rare cause of early neurological deterioration in acute stroke patients undergoing intravenous thrombolysis, with a different temporal pattern compared with that of symptomatic ICH.

Aged↗
PubMed2006

Good outcomes in ischemic stroke patients treated with intravenous thrombolysis despite regressing neurological symptoms.

BACKGROUND AND PURPOSE: We evaluated the clinical course of 19 acute stroke patients with rapid early improvement of neurological deficit within the 3-hour window, treated with intravenous thrombolytics. RESULTS: No patient demonstrated a neurological deterioration during hospitalization. National Institutes of Health Stroke Scale (NIHSS) scores at therapy decision and discharge were 5 (4 to 6) and 0.5 (0 to 1.5), respectively. At 3-month follow-up, 1 patient had died; in remaining patients, NIHSS was 0 (0 to 1) and modified Rankin Scale 0.5 (0 to 1; < or =1 in 15 patients). CONCLUSIONS: Withholding of intravenous thrombolysis because of spontaneous early regression of neurological symptoms may not be justified.

Adult↗
PubMed2006

Immunomodulatory synergy by combination of atorvastatin and glatiramer acetate in treatment of CNS autoimmunity.

One approach to improving efficacy in MS therapy is to identify medications that provide additive or synergistic benefit in combination. Orally administered cholesterol-lowering HMG-CoA reductase inhibitors (known as statins), which exhibit immunomodulatory properties and are effective in treatment of the MS model EAE, are being tested in MS. As atorvastatin can enhance protective Th2 responses and has a different mechanism of action than glatiramer acetate (GA), a parenterally administered immunomodulatory agent approved for MS treatment, we tested whether the combination of these agents could be beneficial in EAE. Combination therapy using suboptimal doses of atorvastatin and GA prevented or reversed clinical and histologic EAE. Secretion of proinflammatory Th1 cytokines was reduced--and conversely Th2 cytokine secretion was increased--in these mice, but not in mice treated with each drug alone at the same doses. Monocytes treated with the combination of suboptimal doses of atorvastatin and GA secreted an antiinflammatory type II cytokine pattern and, when used as APCs, promoted Th2 differentiation of naive myelin-specific T cells. Our results demonstrate that agents with different mechanisms of immune modulation can combine in a synergistic manner for the treatment of CNS autoimmunity and provide rationale for testing the combination of atorvastatin and GA in MS.

Animals↗
PubMed2005

Antibody responses against galactocerebroside are potential stage-specific biomarkers in multiple sclerosis.

BACKGROUND: Galactocerebroside, the major glycolipid of central nervous system myelin, is a known target for pathogenic demyelinating antibody responses in experimental allergic encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). OBJECTIVE: To address the importance of anti-galactocerebroside (alpha-GalC) antibodies in MS and to evaluate them as biomarkers of disease. METHODS: alpha-GalC IgGs were quantified from sera of patients with MS and in marmoset EAE by a new immunosorbent assay. RESULTS: We report a significant difference in serum alpha-GalC IgG titers between patients with relapsing-remitting (RR)-MS and healthy controls (HCs; P < .001). The frequencies of alpha-GalC antibody-positive subjects (alpha-GalC titers > or = mean HC titers+3 SD) are also significantly elevated in RR-MS compared with HC (40% vs 0%; P = .0033). Immunoaffinity purified alpha-GalC IgGs from human serum bind to cultured human oligodendrocytes, indicating that the ELISA detects a biologically relevant epitope. Corroborating these findings, alpha-GalC antibody responses in marmoset EAE were similarly found to be specifically associated with the RR forms and not the peracute or progressive forms, in contrast with other anti-myelin antibodies (P = .0256). CONCLUSION: (1) alpha-GalC antibodies appear MS-specific and are not found in healthy subjects, unlike antibodies against myelin proteins; (2) when present, alpha-GalC antibodies identify mostly RR-MS and may be an indicator of ongoing disease activity. This novel assay is a suitable and valuable method to increase accuracy of diagnosis and disease staging in MS.

Adult↗
PubMed2004

Frontline: Epitope recognition on the myelin/oligodendrocyte glycoprotein differentially influences disease phenotype and antibody effector functions in autoimmune demyelination.

Preliminary observations of humoral immunity against the myelin oligodendrocyte glycoprotein (MOG) in experimental allergic encephalomyelitis (EAE) and human multiple sclerosis (MS) suggest that a subset of anti-MOG autoantibodies directed against conformational epitopes is of pathogenic predominance. Here, we provide proof that in marmoset EAE, autoantibodies reactive against conformational epitopes of MOG are not only responsible for aggravating demyelination, but also an essential factor for disease dissemination in space within the central nervous system, a hallmark for typical forms of human MS. In terms of effector mechanisms, IgG deposition and complement activation occur exclusively in association with presence of these conformational antibodies, while microglial/macrophage activation appears to be a common immunopathological finding regardless of the fine determinant specificity of anti-MOG antibodies. These findings highlight for the first time the complex heterogeneity of function and pathogenicity in the polyclonal anti-MOG antibody repertoire of outbred species. Because the linear and conformational antibody determinants of MOG are shared between marmosets and humans, these results are directly relevant to understanding effector mechanisms of organ damage in MS.

Animals↗
PubMed2002

Molecular characterization of antibody specificities against myelin/oligodendrocyte glycoprotein in autoimmune demyelination.

Myelin/oligodendrocyte glycoprotein (MOG) is a target antigen for myelin-destructive Abs in autoimmune central nervous system demyelinating disorders. Little is known about the molecular and structural basis of these pathogenic Ab responses. Here, we have characterized anti-MOG Ab specificities in the marmoset model of experimental allergic encephalomyelitis, by means of a combinatorial IgG-Fab library. We found that a diverse population of Ig genes encodes for auto-Abs that exclusively recognize conformation-dependent antigenic targets on MOG. These antigenic domains correspond to exposed epitopes in vivo, as the Fab fragments recognize native MOG in situ in marmoset brain tissue. The Ab fragments described here represent Ab specificities that are common constituents of the humoral immune repertoire against MOG in outbred populations, as demonstrated by their ability to displace native anti-MOG Abs present in sera from MOG-immune marmosets and patients with multiple sclerosis. Furthermore, neuropathological analysis and characterization of Ab epitope specificities in animals immunized with MOG or MOG-derived peptides revealed that only conformation-dependent Abs are associated with demyelinating activity, suggesting that epitope recognition is an important factor for Ab pathogenicity. Our findings provide novel and unexpected knowledge on the diversity of anti-MOG Ab responses in nonhuman primates and humans, and will permit the dissection of pathogenic auto-Ab properties in multiple sclerosis.

Amino Acid Sequence↗
PubMed2002

Approved and future pharmacotherapy for multiple sclerosis.

BACKGROUND: Pharmacotherapy for relapsing-remitting multiple sclerosis (MS) advanced with the demonstration that interferon beta and glatiramer acetate improve the clinical course of this disease. Mitoxantrone is the first drug approved by the Food and Drug Administration for treatment of secondary progressive MS. Despite this progress, the agents presently available are only partially effective, are difficult to administer, and may have significant side effects. Several orally administered immunomodulatory agents are presently being evaluated for treatment of MS. One class of drugs, HMG CoA inhibitors (statins), is safe and well-tolerated and could become another mainstay of MS therapy. REVIEW SUMMARY: This article reviews the clinical evidence for approved MS therapies and discusses their mechanisms of action. Furthermore, the clinical and laboratory data suggesting a potential role for statins in MS therapy are discussed. CONCLUSIONS: Although treatment with interferon beta, glatiramer acetate, and mitoxantrone, the approved therapies, provide important treatment options for patients with relapsing-remitting MS and secondary progressive MS, the potential benefits of other medications, including statins, should be explored in controlled clinical trials.

Journal Article↗