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Biomedical subjects

M Marziniak

Publications and source records attributed to M Marziniak.

10 recordsLinked to original sources
PubMed2006

Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy.

In this report, we describe the first known patient with a deficiency of sterol carrier protein X (SCPx), a peroxisomal enzyme with thiolase activity, which is required for the breakdown of branched-chain fatty acids. The patient presented with torticollis and dystonic head tremor as well as slight cerebellar signs with intention tremor, nystagmus, hyposmia, and azoospermia. Magnetic resonance imaging showed leukencephalopathy and involvement of the thalamus and pons. Metabolite analyses of plasma revealed an accumulation of the branched-chain fatty acid pristanic acid, and abnormal bile alcohol glucuronides were excreted in urine. In cultured skin fibroblasts, the thiolytic activity of SCPx was deficient, and no SCPx protein could be detected by western blotting. Mutation analysis revealed a homozygous 1-nucleotide insertion, 545_546insA, leading to a frameshift and premature stop codon (I184fsX7).

Adult↗
PubMed2006

Triptans in orgasmic headache.

Orgasmic headache (headache associated with sexual activity type 2 according to the International Headache Society classification) is a sudden severe headache which occurs at orgasm. Experiences with triptan therapy are described. Two out of four patients with severe headache continuing for >2 h had a positive response to acute triptan therapy. Two out of three patients using triptans as short-term prophylaxis reported a reliable response on several occasions. Triptans might be a treatment option to shorten orgasmic headache attacks after the diagnosis is clear and, particularly, subarachnoid haemorrhage has been excluded. In patients who chose to predict their sexual activity, short-term prophylaxis with oral triptans 30 min before sexual activity might be a therapeutic option in those not responsive to or not tolerating indomethacin.

Adult↗
PubMed2005

A functional serotonin transporter gene polymorphism is associated with migraine with aura.

An association study was performed in 197 migraineurs with regard to a functional serotonin (5-HT) transporter (5-HTT) gene promoter polymorphism that leads to low or high 5-HT uptake activity. The frequency of the less active short allele was increased in migraineurs with aura but not in migraineurs without aura in comparison with the control population (p < 0.001). This indicates that the 5-HTT may be involved in the polygenic etiology of migraine with aura.

Alleles↗
PubMed2004

Association analysis of the functional monoamine oxidase A gene promotor polymorphism in migraine.

Migraine affects about 15% of the adult population. Serotonergic and dopaminergic systems are believed to be involved in its pathophysiology. One of the key enzymes in the degradation of serotonin and to a lesser extent of dopamine is monoamine oxidase A (MAO-A). In this study we investigated a functionally relevant gene-linked polymorphic repetitive sequence (LPR) located approximately 1.2 kb upstream of the ATG codon in the MAO-A-promotor gene. 119 patients with migraine and 229 controls were tested. The allelic distribution of the controls and the migraine patients did not show significant differences with respect to the low- and high-activity alleles. Moreover, effectiveness of the potent serotonergic antimigraine agents, triptans, which are metabolized by MAO-A, was clinically not affected by the MAO-A-LPR in our patients. These findings thus indicate that there is no association between the functional MAO-A-LPR and susceptibility to migraine.

Adult↗
PubMed2002

Small fibre neuropathy in sarcoidosis.

Some patients with sarcoidosis have unexplained pain and dysaesthesia. We did quantitative sensory testing in 31 sarcoidosis patients with pain or autonomic dysfunction. 25 patients had reduced warmth sensitivity, cold sensitivity, or both. Intraepidermal nerve fibre density (IENFD) was measured in punch biopsy skin samples in seven consecutive patients. All seven patients had reduced IENFD compared with controls, which confirmed the presence of small fibre neuropathy in these patients. Some patients with sarcoidosis may have small fibre neuropathy with autonomic involvement.

Adult↗
PubMed2002

Impaired sensory function in heterozygous P0 knockout mice is associated with nodal changes in sensory nerves.

Mice heterozygously deficient in the major myelin component P0 are an established model of an inherited neuropathy and show signs of myelin degeneration in motor nerves. Unlike the case in patients, the sensory nerves are only mildly affected in the mouse mutants and do not show features indicative of myelin degeneration. Unexpectedly, by applying established behavioral tests, we found sensory deficits, as reflected by raised withdrawal thresholds to mechanical and thermal stimuli, whereas behavioral signs of a painful neuropathy were not detectable. By electron microscopy of longitudinal sections of sensory nerves, we found abnormalities in nodes of Ranvier comprising enlarged nodal gaps and poorly developed nodal Schwann cell microvilli. These alterations might be causally linked to the sensory deficits in the absence of profound myelin degeneration in the sensory nerves of the mutants.

Animals↗
PubMed2001

Combined epineurial therapy with neutralizing antibodies to tumor necrosis factor-alpha and interleukin-1 receptor has an additive effect in reducing neuropathic pain in mice.

Monotherapy with antibodies to tumor necrosis factor-alpha (TNF) or interleukin-1 receptor 1 (IL-1R1) reduces hyperalgesia in an animal model of painful neuropathy. Here we investigated whether combined therapy with epineurial anti-TNF and anti-IL-1R1 antibodies produces a further advantage. C57BL/6 mice with a chronic constrictive injury of one sciatic nerve were treated epineurially with neutralizing antibodies to either IL-1R1 or TNF alone or with a combined application of neutralizing antibodies to TNF and IL-1R1. Combined treatment with anti-IL-1R1 and anti-TNF antibodies markedly reduced thermal hyperalgesia and mechanical allodynia more effectively than monotherapy with either antibody. There were no detectable differences in IL-1beta and TNF endoneurial protein expression between animals with monotherapy and combined treatment. We conclude that combined anti-cytokine therapy may be a useful strategy in the treatment of neuropathic pain.

Animals↗
PubMed2001

Etanercept reduces hyperalgesia in experimental painful neuropathy.

Etanercept, a recombinant tumor necrosis factor receptor (p75)-Fc fusion protein competitively inhibits tumor necrosis factor-alpha (TNF). Etanercept has been successfully used in patients with rheumatoid arthritis, where it reduces pain and inflammation. Because locally produced proinflammatory cytokines play a role in pain after nerve injury, we investigated whether etanercept can reduce pain and hyperalgesia in an animal model of painful neuropathy, the chronic constriction injury of the sciatic nerve. C57BL/6 mice received etanercept or sham treatment by local near-nerve injection to the injured nerve or by systemic application. Treatment with etanercept reduced thermal hyperalgesia and mechanical allodynia significantly in both modes of application. The effect of etanercept was present in animals that were treated from the time of surgery and in those that were treated from day 6, when hyperalgesia was already present. These results suggest the potential of etanercept as a treatment option for patients with neuropathic pain.

Animals↗