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Biomedical subjects

H Wiethölter

Publications and source records attributed to H Wiethölter.

At least 19 recordsLinked to original sources
PubMed2004

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Clinical Trials as Topic↗
PubMed2002

Analysis of immunoregulatory T-helper cell subsets in patients with multiple sclerosis: relapsing-progressive course correlates with enhanced T H1, relapsing-remitting course with enhanced T H0 reactivity.

In this study, we analysed the recall antigen-induced cytokine production by peripheral blood mononuclear cells (PBMC) from 31 patients with multiple sclerosis (MS) with a relapsing-remitting (rr) and a relapsing-progressive (rp) course and from 40 healthy controls. Cells were stimulated with purified protein derivative (PPD; type 1 response) and tetanus toxoid (TT; type 2 response). Cytokines were determined in the supernatants by ELISA. One of the interesting findings was that healthy controls showed more frequently an IL-5 production after incubation with TT than MS-patients (68% vs.37%; p<0.01), while the type 1 reactivity was only slightly enhanced in MS patients as compared to the controls. However, within the MS patients, there was a significant difference in the incidence of the type 1 reactivity comparing patients with an rp and an rr course (60% vs. 24%; p<0.05). Furthermore, the frequency of a type 0 profile (simultaneous PPD-induced IFN-gamma and TT-induced IL-5 production) was fourfold higher in rr than in the rp patients (43% vs. 10%, p<0.05). In vitro analysis of cytokine profiles in MS could therefore be an interesting approach to evaluate the prognosis of MS (rr vs. rp) already at the beginning of the disease. Thus, it seems that the presence of a type 0 profile is a valid indicator for a favorable course, while a type 1 profile is rather associated with rp MS.

Adult↗
PubMed2000

[The stiff-man syndrome with diabetes mellitus type 1 and autoimmune thyroiditis].

HISTORY AND ADMISSION FINDINGS: A 54-year-old woman with type 1 diabetes of about 2 years' duration developed painful cramps in the muscles of the abdominal wall, the back and the thighs. On admission physical examination confirmed markedly increased tone of the muscles of the trunk and those proximal to it. INVESTIGATIONS: Markedly increased amounts of anti-GAD (glutamic acid decarboxylase) antibodies were present in both serum and cerebrospinal fluid (CSF). Electroneurography and -myography revealed mild polyneuropathy but no other neurological abnormality. DIAGNOSIS, TREATMENT AND COURSE: Suspected stiff-man syndrome (SMS) was confirmed by the increased anti-GAD antibodies and the marked improvement on gradually increasing doses of clonazepam. The autoimmune syndrome affected several organ systems: central nervous system (SMS), pancreas (diabetes), thyroid (immuno-thyroiditis). Immunosuppressive treatment with azathioprine was begun. The patient remains in good general condition 22 months after the initial diagnosis, and there have been no new organ involvement. CONCLUSION: It is important to include SMS in the differential diagnosis, even though the symptoms are not those of the full-blown picture of this rare disease. Absence of muscle cramps and myoclonus but presence of depressive symptoms can easily result in misdiagnosis, preventing early initiation of effective symptomatic treatment.

Azathioprine↗
PubMed1999

[Continuing medical education (CME) in neurology. Concept of the German Society of Neurology (DGN) and the Neurology Section of the Professional League of German Neurologic Medicine (BVDN)].

Continuous medical education in Neurology (CME-Neurology) has been promoted in a concept organized by both the German society of neurology, German association for occupational interests of neurologists and psychiatrists). CME-Neurology has been started in January 1999 and is closely adapted to the CME guidelines of neurology section of UEMS and EFNS. The program shall serve to the maintenance and upgrading of knowledge skills and competence of postgraduate training in neurology.

Education, Medical, Continuing↗
PubMed1996

The antibody repertoire in experimental allergic neuritis: evidence for PMP-22 as a novel neuritogen.

Experimental allergic neuritis (EAN) is an autoimmune disease that serves as an animal model for the Guillain-Barré syndrome (GBS). In both disorders there is still great uncertainty as to the significance and diversity of autoantibodies involved. We focused on the characterization of serum antibody production in response to various peripheral nervous system (PNS) myelin proteins during the course of actively induced EAN in Lewis rats. These data were compared with EAN induced by adoptive transfer of P2-specific CD4+ T cells (AT-EAN) and with inoculation with complete Freund's adjuvant (CFA) alone. Semiquantitative Western blotting was applied to measure serum IgM and IgG titers against specific myelin proteins, including P2, P0, myelin basic protein (MBP), myelin-associated glycoprotein (MAG) and PMP-22. Considerable differences in the dynamics of antibody titers against individual myelin proteins were observed in active EAN and after inoculation with CFA alone. Our data suggest a pathogenic role of IgM antibodies against HNK adhesion carbohydrate epitope expressing PNS proteins P0, MAG and PMP-22. Among these, PMP-22, a novel candidate neuritogen may be of particular relevance. Thus, we provide evidence for the involvement of antibody-mediated immune response in actively induced EAN and a basis for similar studies on related human disorders such as GBS or other demyelinating neuropathies.

Animals↗
PubMed1994

Critical time of exposure of the rabbit inferior alveolar nerve to Carnoy's solution.

To reduce the recurrence of keratocysts, tanning of the epithelial lining with modified Carnoy's solution has been advocated as an ancillary procedure. This agent has occasionally been reported to induce long-lasting local neurotoxicity, when the inferior alveolar nerve (IAN) was located within the bony cavity of larger cysts. As the severity of the neurologic damage depends on the tissue penetration of the solution, a critical exposure time must be assumed. To substantiate this hypothesis, rabbit IANs were decorticated over an approximate length of 1 cm and soaked with modified Carnoy's solution for periods from 30 seconds to 10 minutes. Sensory nerve function was monitored using somatosensory evoked potentials. Exposures up to 2 minutes did not result in any electrophysiologic abnormality. Exposure for 3 minutes led to either normal or rudimentary evoked potentials. After exposure of 5 minutes, and invariably after 10 minutes, the evoked potentials from the IAN were absent. Nerve segments were removed for histologic examination and the penetration depth of the Carnoy's solution was identified by staining with the Berlin-blue reaction. The involved areas were morphometrically evaluated and they reflected the electrophysiological findings. Transmission electron microscopy showed morphologic changes confined to the outer nerve sheaths (epineurium and perineurium) after exposure of 3 minutes. Exposure of 5 minutes and longer resulted in involvement of both the nerve sheaths and their axonal contents, with disruption and disintegration of the neural tissue. This study clearly supports the hypothesis that contact of a peripheral nerve (ie, IAN) with Carnoy's solution carries a time-related risk to produce acute sensory impairment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1994

Recovery of the hypothalamic-pituitary-adrenal axis from suppression by short-term, high-dose intravenous prednisolone therapy in patients with MS.

We have studied the recovery of the hypothalamic-pituitary-adrenal (HPA) axis from inhibition by short-term, intravenous high-dose, corticosteroid therapy (IVHDCT) without subsequent oral replacement therapy in 10 patients with relapsing-remitting or progressive multiple sclerosis (MS) using the human corticotrophin-releasing hormone (hCRH) test. There was significant HPA suppression with profoundly decreased basal and peak plasma ACTH and cortisol levels 24 h after cessation of therapy. However, at 48 h the pituitary response was greatly enhanced with peak ACTH concentrations rising by more than 100% over baseline values in 7 of 10 patients. Basal and stimulated ACTH concentrations returned to pre-treatment levels at 120 h. Basal and stimulated plasma cortisol levels remained subnormal in 6 patients 120 h after IVHDCT. We conclude that IVHDCT without oral replacement therapy in MS patients is endocrinologically safe.

Adrenocorticotropic Hormone↗
PubMed1993

Intrathecal IgM response in disseminated cerebrospinal metastasis from malignant melanoma.

Neurological complications are a major cause of morbidity and mortality in patients with disseminated malignant melanoma. We have studied and correlated clinical and cerebrospinal fluid (CSF) findings in 20 patients with central nervous system metastases from malignant melanoma including 8 patients with metastatic meningeal melanomatosis (MMM) and 12 patients with solid cerebral metastases (SCM). The putative CSF tumor markers, fibronectin and beta 2-microglobulin, were elevated significantly in MMM but not in SCM patients. A prominent increase in the IgM index, which reflects intrathecal B-cell stimulation, and a rise of IgG index, interleukin-6, and tumor necrosis factor-alpha in MMM patients provide preliminary evidence for a local intrathecal immune response triggered by melanoma cell invasion of the subarachnoid space.

Humans↗
PubMed1993

Photochemically induced experimental ischemic neuropathy: a clinical, electrophysiological and immunohistochemical study.

A new experimental model of focal peripheral nerve infarction is presented. Ischemia was produced in 12 rats by intravascular thrombosis induced by the photochemical reaction of systemically injected rose bengal to the local application of light from a cold light source. Clinical, electrophysiological and immunohistochemical techniques were used to monitor the pathology and the time course of experimental ischemic neuropathy (EIN) of the sciatic nerve. Primary axonal neurofilament disintegration was detectable 4-24 h after illumination and was followed by wallerian degeneration within the first week. At 7 days, there was a secondary disruption of myelin sheaths accompanied by massive infiltration of macrophages and phagocytosis of the necrotic debris. The majority of detected macrophages were derived from circulating blood monocytes which had invaded the nerve. Two weeks after the initial lesions, degeneration had advanced without any signs of regeneration or remyelination. Electrophysiological recordings corroborate the findings of primary axonal degeneration and failure of regeneration up to 2 weeks after the lesion.

Action Potentials↗
PubMed1993

Thymectomy and azathioprine have no effect on the phenotype of CD4 T lymphocyte subsets in myasthenia gravis.

The influence of thymectomy and long term immunosuppression on the phenotype of CD4 T lymphocyte subsets, which were defined by the restricted expression of CD45RA and CD45RO markers, was studied by double immunofluorescence in 29 patients in different clinical stages of generalised myasthenia gravis. In the acute stage of myasthenia, before thymectomy and immunosuppression, no differences in CD4 subsets were observed in the peripheral blood from nine patients and 21 matched controls. Four to seven weeks after thymectomy, there was a slightly decreased proportion of CD4+CD45RO+ (UCHL1+) memory cells (p < 0.05, paired t test). Patients on steroids showed a more pronounced decrease of CD4+CD45RO+ cells suggesting, in addition, a drug-related effect. CD4 subsets (CD45RA, CD45RO, and CD29 positive) in the peripheral blood compartment remained largely stable over 18 to 24 months thereafter. In addition, CD4 subsets were examined in 20 patients with myasthenia gravis who had had a thymectomy between two and 17 years before. With the exception of patients on steroids, there were no differences in CD4 subsets in patients on or off azathioprine. These data did not show any relation of CD4 T cell subsets to the clinical course of myasthenia, or significant changes due to thymectomy, or immunosuppression with azathioprine. These results also complement the authors' clinical experience that thymectomy in adults does not leave a deficit in cell-mediated immunity. The slight change associated with steroid treatment might deserve further attention.

Adolescent↗
PubMed1993

A characteristic ganglioside antibody pattern in the CSF of patients with amyotrophic lateral sclerosis.

Paired cerebrospinal fluid and serum samples of patients with amyotrophic lateral sclerosis (n = 35) revealed no consistent abnormalities of CSF cell count, CSF albumin, CSF IgG, CSF IgM, IgG or IgM index, or oligoclonal immunoglobulin band formation in the CSF. Determination of IgG and IgM CSF and serum antibodies to gangliosides GM1, GM2, GM3, AGM1, GD1a, GD1b, and GT1b showed a characteristic pattern which allowed the differentiation of amyotrophic lateral sclerosis from controls and from patients with other neurological disorders including multiple sclerosis. Specifically, patients with the disease had elevated CSF IgM antibodies to all gangliosides except AGM1. The lack of correlation between the CSF findings and corresponding serum antibodies suggests a chronic, compartmental, intrathecal immune response of low activity in amyotrophic lateral sclerosis. Whether this immune response is primary and of pathogenetic significance, or an epiphenomenon of neuronal degeneration, remains to be investigated.

Adult↗
PubMed1992

Tumor cell dissemination triggers an intrathecal immune response in neoplastic meningitis.

The intrathecal immune response in neoplastic meningitis (NM) was studied by quantitation of immune parameters such as immunoglobulin G (IgG); IgM; interleukins (IL) 1, 2, 4, and 6; soluble IL-2 receptors (sIL-2R); interferon gamma (IFNy); tumor necrosis factor-alpha (TNF alpha); and three tumor markers, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and fibronectin (FN), in 47 paired cerebrospinal fluid (CSF) and serum samples from patients with NM from different carcinomas, malignant melanoma, and lymphoma. Elevated IgG and IgM indices, CSF oligoclonal Ig bands, and CSF IL-6 indicated an intrathecal immune activation in most patients with NM. Results for IL-1, IL-2, and IL-4 were always negative. sIL-2R and IFNy were detected occasionally but not associated with specific malignant neoplasms. CSF TNF alpha was detected only in NM from cases of malignant melanoma. None of the immune parameters proved useful for the differentiation of NM from autoimmune or inflammatory conditions. Immune parameters were not correlated with tumor markers CEA, AFP, or FN. Results for AFP were positive only in a case of glioblastoma. CEA was a useful and specific diagnostic parameter in carcinomatous NM. CSF FN levels frequently were elevated but are not specific for NM.

Breast Neoplasms↗
PubMed1992

T cells from normal and myasthenic individuals recognize the human acetylcholine receptor: heterogeneity of antigenic sites on the alpha-subunit.

The alpha-subunit of the nicotinic acetylcholine receptor is the major target of the autoimmune response in myasthenia gravis. We investigated the proliferative response of T cells from patients with myasthenia gravis and healthy volunteers to recombinant polypeptides of the human acetylcholine receptor including the full-length alpha-subunit (alpha 1-437). T cells from 20 (71%) of 28 patients and 7 (37%) of 19 healthy volunteers responded in primary cultures. Subsequently, specific T-cell lines were established: CD4+, CD8-, UCHL1+, and major histocompatibility complex (MHC) class II-restricted. Using a set of fragments of the alpha-subunit, major antigenic sites could be localized on the extracellular, N-terminal part of the molecule as well as close to the C-terminus. The T-cell response was heterogeneous, both among different individuals and among T-cell lines from a single donor. These T cells did not cross-react with Torpedo acetylcholine receptor, which was previously used as a substitute for human muscle acetylcholine receptor, suggesting that the T cells had a bias for unique human sequences. A single antigenic fragment could be presented in the context of different MHC class II molecules, and different fragments could be presented in the context of the same MHC molecule. This supports earlier observations of considerable heterogeneity in dealing with acetylcholine receptor as an autoantigen on the level of both T cells and antigen-presenting cells. The data also demonstrate that acetylcholine receptor-specific T cells are present in the normal immune repertoire, and emphasize the role of immune regulation for maintaining a state of tolerance.

Animals↗