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Biomedical subjects

Volker Limmroth

Publications and source records attributed to Volker Limmroth.

At least 19 recordsLinked to original sources
PubMed2006

CD4+CD25+FoxP3+ T lymphocytes fail to suppress myelin basic protein-induced proliferation in patients with multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disorder directed against self antigens of the central nervous system. CD4(+)CD25(+)FoxP3(+) regulatory T cell (T(reg)) mediated suppression is an essential mechanism of self-tolerance. We studied whether changes in the suppressive function of a mixture of CD25(high) and CD25(intemediate) expressing T(reg) cells in myelin basic protein (MBP)-induced proliferation occurred in untreated MS patients. Suppression of MBP-induced proliferation was observed in 13 out of 29 (45%) MS patients; this was significantly (p<0.05) less compared with 17 out of 19 (89%) healthy individuals. Relative T(reg) counts was significantly increased in MS patients (mean+/-S.D.; 20+/-8%) compared with healthy individuals (15+/-5%). These findings suggest that impaired T(reg) function may be involved in pathogenesis of MS.

Adult↗
PubMed2006

Secondary myelodysplastic syndrome following long-term treatment with azathioprine in patients with multiple sclerosis.

Azathioprine (Aza) is a widely used immunosuppressive drug in multiple sclerosis (MS) treatment. Recently, the incidence of secondary myelodysplastic syndromes (sMDS) associated with a poor prognosis was found to be elevated in patients treated with Aza for non-malign disorders. Three hundred and seventeen MS patients were retrospectively analysed and complete blood counts were examined for those exposed to Aza. We identified one case of sMDS (cumulative dose 627 g) in a young patient and two further malignancies (cumulative doses 27 g and 54 g) in the Aza group (n = 81; 3.7%). In the non-Aza (n = 236) group, five malignancies (2.1%, P = 0.419) were identified. Including our patient, four cases of sMDS after long-term Aza therapy in MS have been reported so far. Cases suggest a time- and dose-dependent risk of sMDS in long-term therapy of MS with Aza. Long-term Aza therapy needs careful monitoring.

Adolescent↗
PubMed2005

Effects of interferon-beta 1a on the hypothalamic-pituitary-adrenal axis, leukocyte distribution and mood states in multiple sclerosis patients: results of a 1-year follow-up study.

Acute interferon-beta (IFN-beta) administration transiently activates the hypothalamic-pituitary-adrenal (HPA) axis, increases granulocytes, and reduces lymphocytes in peripheral blood. To test whether these effects are still present after long-term treatment, 13 patients with relapsing-remitting multiple sclerosis were analyzed at baseline, and 1, 2, 4, and 8 h after IFN-beta 1a injection at two occasions: at the initial administration and after 1 year of continuous treatment. Long-term treatment reduced the responsiveness of the HPA axis to the injection, and abolished the distributional changes in leukocyte numbers. One-year treatment with IFN-beta 1a did not induce mood alterations as assessed by the Profile of Mood States. These results suggest that long-term IFN-beta therapy has a profound impact on leukocyte distribution and the neuroendocrine response to the drug.

Adjuvants, Immunologic↗
PubMed2005

Behavioral conditioning with interferon beta-1a in humans.

Behavioral conditioning is one of the most impressive demonstrations of brain-immune system interaction. Numerous animal studies have demonstrated behavioral conditioned effects on immune functions, however, human studies are rare. We investigated whether it is possible to behaviorally condition the acute response to interferon (IFN)beta-1a. In a double-blind placebo-controlled study, 30 healthy subjects received a single injection of IFN(beta)-1a (6MIU of REBIF, Serono International) (unconditioned stimulus, UCS) together with a novel drink (conditioned stimulus, CS). Blood was drawn at baseline, 4, 8, and 24 h after drug administration. Within the first 8 h peripheral granulocytes significantly increased, while monocytes, lymphocytes, T-, B- and natural killer (NK) cell numbers were significantly reduced. In parallel, body temperature, heart rate, norepinephrine and interleukin (IL)-6 plasma levels were heightened within 8 h after injection. 8 days later, all previously IFN(beta)-treated subjects received a subcutaneous placebo (NaCl) injection, but only 15 subjects were re-exposed to the CS (experimental group), while a control group (N=15) drank water and an additional group of subjects (n=8) remained untreated (untreated group). Blood sampling was performed at baseline and at 4, 8, and 24 h. Re-exposition to the CS did not elicit conditioned responses in the experimental group. Moreover, no differences were observed between groups. These data provide negative findings regarding behavioral conditioning of cytokine effects in humans employing a one-trial learning paradigm.

Adult↗
PubMed2005

G protein-coupled receptor kinase 2 in multiple sclerosis and experimental autoimmune encephalomyelitis.

Many modulators of inflammation, including chemokines, neuropeptides, and neurotransmitters signal via G protein-coupled receptors (GPCR). GPCR kinases (GRK) can phosphorylate agonist-activated GPCR thereby promoting receptor desensitization. Here we describe that in leukocytes from patients with active relapsing-remitting multiple sclerosis (MS) or with secondary progressive MS, GRK2 levels are significantly reduced. Unexpectedly, cells from patients during remission express even lower levels of GRK2. The level of GRK2 in leukocytes of patients after stroke, a neurological disorder with paralysis but without an autoimmune component, was similar to GRK2 levels in cells from healthy individuals. In addition, we demonstrate that the course of recombinant myelin oligodendrocyte glycoprotein (1-125)-induced experimental autoimmune encephalomyelitis (EAE), an animal model for MS, is markedly different in GRK2(+/-) mice that express 50% of the GRK2 protein in comparison with wild-type mice. Onset of EAE was significantly advanced by 5 days in GRK2(+/-) mice. The earlier onset of EAE was associated with increased early infiltration of the CNS by T cells and macrophages. Although disease scores in the first phase of EAE were similar in both groups, GRK2(+/-) animals did not develop relapses, whereas wild-type animals did. The absence of relapses in GRK2(+/-) mice was associated with a marked reduction in inflammatory infiltrates in the CNS. Recombinant myelin oligodendrocyte glycoprotein-induced T cell proliferation and cytokine production were normal in GRK2(+/-) animals. We conclude that down-regulation of GRK2 expression may have important consequences for the onset and progression of MS.

Animals↗
PubMed2005

Medication-overuse headache.

Medication-overuse headache (MOH) can be caused by almost all anti-headache drugs including analgesics, ergots, triptans, and combined preparations The prevalence of chronic daily headache (CDH) appears to be between 2% and 4% in the general population. Current epidemiologic studies suggest that MOH accounts for approximately 50% of these cases. The pathophysiology of MOH remains unclear. The only therapy is withdrawal from the overused substances. Prednisone decreases the duration of headache in the first days of withdrawal therapy. The only strategy to reduce the prevalence of MOH is to prevent the development of MOH in the first place by restriction of anti-headache drugs and constant education of patients.

Analgesics↗
PubMed2005

Comparison of intravenous valproate with intravenous lysine-acetylsalicylic acid in acute migraine attacks.

OBJECTIVE: The study compared efficacy and tolerability of intravenous valproate (iVPA) with intravenous lysine-acetylsalicylic acid (iLAS) in acute migraine attacks. Background.-iLAS has been proven to be a highly effective treatment in acute migraine attacks, but it is not available in many countries and contraindicated in patients with asthma or peptic ulcers. Current data suggest that iVPA may be effective in the treatment of acute migraine attacks. DESIGN/METHODS: In this randomized, double-blind, parallel-group phase-II study, 40 patients with acute migraine attacks (onset <5 hours, severe or moderate headache on a four-point IHS scale) alternately received iVPA 800 mg or iLAS 1000 mg. Primary outcome criteria were the percentage of patients reporting pain relief after 1 hour and patients who remained sustained pain free for 24 hours following drug administration. Secondary outcome criteria were relief of pain and associated migrainous symptoms (nausea, photophobia, and phonophobia) at 1, 2, 24, and 48 hours following drug administration. RESULTS: There were no significant differences in demographic and clinical features between both treatment groups. Percentage of pain relief after 1 hour in the iVPA and iLAS groups were 25% and 30%, respectively, and of sustained pain free for 24 hours were 20% and 30%, respectively, without significant differences (P = 1 and P= .72, respectively). Both drugs improved associated migrainous symptoms without significant differences at the different time points, but again with a trend in favor of iLAS. No adverse events were observed. CONCLUSION: Both drugs were effective in acute migraine attacks with a trend in favor of iLAS. As both drugs were well tolerated, further studies with higher doses of iVPA for the treatment of acute migraine attacks are recommended.

Acute Disease↗
PubMed2005

Evidence-based medicine in migraine prevention.

Migraine headache is a chronic, painful, disabling and potentially progressive, condition primarily occurring in early and middle adulthood. For many patients, daily activities are impaired by the sudden and unpredictable occurrence of migraine attacks. In recent years, significant progress has been made in the field of migraine treatment. For the acute treatment of migraine attacks, 5-hydroxytryptophan(1B/D) agonists (so called triptans), were the most innovative development, successfully aborting attacks in less than 1 h. The search for innovative drugs usable for migraine prevention, however, was less successful, mainly due to the lack of reliable and predictive animal models. Recently, neuromodulators such as valproic acid and topiramate, initially developed as anticonvulsants, have been shown in large clinical trials to be effective in the prevention of migraine. As for the acute treatment of migraine attacks more than 10 years ago, large clinical trial programs are now setting new standards for evidence-based medicine in migraine prevention. This review summarizes the current options in migraine prevention with special emphasis on clinical trial design and new developments such as topiramate.

Adrenergic beta-Antagonists↗
PubMed2005

Medication overuse headache in patients with primary headache disorders: epidemiology, management and pathogenesis.

Medication overuse headache (MOH) is a common medical condition that is associated with considerable long-term morbidity and disability. Patients experiencing MOH have primary headache disorders (migraine, tension-type headache [TTH] or the combination of migraine and TTH) that change to a pattern of daily or near-daily headaches over a period of years or decades following the overuse of symptomatic headache medications. Overused drugs include analgesics, ergot alkaloids, serotonin 5-HT(1B/1D) receptor agonists ('triptans') and medications containing barbiturates, codeine, caffeine, tranquillisers and mixed analgesics. Affected patients usually have a long history of primary headache, overuse of medications and MOH before they consult a physician for care. Patients with MOH are usually managed in specialist centres by withdrawal of the overused drugs and treatment of withdrawal symptoms (on an inpatient or outpatient basis), headache prophylaxis and limited use of symptomatic acute medications. Most patients respond to this therapy, although the prognosis is not always good and >or=50% may lapse over an initial 5-year follow-up period. The best practical strategy at present is to prevent the overuse of drugs in the first place by patient education and formal management approaches conducted in primary care to treat the primary headache before it changes to MOH. The quality of the clinical evidence on MOH is suboptimal and further biological and clinical research is urgently required to help facilitate the management of these patients more effectively in the future.

Analgesics↗
PubMed2004

In vitro adrenergic modulation of cellular immune functions in experimental autoimmune encephalomyelitis.

OBJECTIVE: To analyze the effects in vitro of alpha- and beta-adrenoceptor agonists on splenocyte proliferation and on proinflammatory cytokine production in splenocytes and peritoneal macrophages (MF) in different stages of EAE. METHODS: Splenocytes and peritoneal macrophages were harvested in the acute phase of EAE and in remission, and from controls. The beta-agonist terbutaline, the alpha(1)-agonist methoxamine, and the alpha(2)-agonist UK-14304 were added with ConA or lipopolysaccharide (LPS). TNF-alpha and IFN-gamma contents in supernatant and splenocyte proliferation were determined. RESULTS: Terbutaline and UK-14304 significantly suppressed TNF-alpha production by MF. However, EAE acute phase rats were resistant to the suppressive effect of UK-14304. Terbutaline significantly suppressed IFN-gamma and TNF-alpha production by splenocytes. EAE acute phase and remission animals showed reduced terbutaline-induced inhibition of IFN-gamma production. CONCLUSIONS: Disturbed sympathetic-immune communication in EAE is characterized by alterations in adrenergic sensitivity via both alpha- and beta-adrenergic pathways.

Adrenergic Agonists↗
PubMed2004

Medication-overuse headache: a worldwide problem.

Medication overuse and subsequent medication-overuse headache (MOH) is a growing problem worldwide. Epidemiological data suggest that up to 4% of the population overuse analgesics and other drugs for the treatment of pain conditions such as migraine and that about 1% of the general population in Europe, North America, and Asia have MOH. Recent clinical studies gave further insights in clinical and pharmacological features, such as critical monthly doses and frequencies. These features seem to vary significantly and depend on the primary headache disorder and the type of drug that is overused. Along with these findings the new international classification of headache disorders has now incorporated additional criteria and new headache entities that will facilitate the diagnosis of MOH. Withdrawal therapy is the only treatment for this disorder and clear restriction of monthly doses is the central requirement for successful prevention.

Diagnosis, Differential↗
PubMed2004

Medication overuse headache.

PURPOSE OF REVIEW: The current literature on medication overuse headache will be reviewed with regard to clinical presentation, pathophysiology, therapy and prognosis in the light of the new headache classification. RECENT FINDINGS: Medication overuse headache is a widely unrecognized medical condition, which according to recent epidemiological studies has evolved to the third most frequent form of headache after tension-type headache and migraine. The first classification of headache disorders from 1988 defined medication overuse headache (formerly called 'drug-induced headache') on the bases of drugs that were available in the 1980s. For the most important anti-headache drugs, including triptans, new data on specific clinical features and more important mean critical monthly dosages and mean critical monthly intake frequencies are now available. Furthermore, recent prospectively conducted studies have revealed rates and predictors of relapse after successful withdrawal. SUMMARY: The newly available data on medication overuse headache may provide the basis for future consensus guidelines for the management of this condition.

Analgesics↗
PubMed2003

Symptomatic migraine and sensitization of trigeminal nociception associated with contralateral pontine cavernoma.

A 38-year-old woman is described with symptomatic strictly right-sided migraine associated with a pontine cavernoma affecting the contralateral (left) nucleus raphe magnus. A persistent facilitation of the right-sided trigeminal nociception was detected interictally using the 'nociception specific' blink reflex, which was more pronounced during the acute attack. This case shows for the first time, an impairment of the anti-nociceptive brainstem nuclei and the facilitation of the trigeminal nociception in the same subject, thus providing further evidence for the key role of the brainstem raphe nuclei in the pathophysiology of migraine.

Adult↗