Encephalo-myelo-radiculo-ganglionitis presenting as pandysautonomia

A 68-year-old man developed pandysautonomia with severe orthostatic dysfunction, fixed heart rate, low serum levels of norepinephrine and epinephrine, absent sympathetic skin responses, and pupillary abnormalities. CSF protein was 92 mg/dl. In spite of a good recovery following corticosteroid administration, a relapse occurred, with accompanying sensory symptoms confined to both arms. Fatal sudden cardiac arrest occurred after 4 months. Autopsy revealed numerous lymphocytic infiltrates, predominantly in autonomic and sensory ganglia and, to a lesser extent, in the nerve roots, spinal cord, and brainstem without evidence for an underlying tumor. This case provides histopathologic evidence for an inflammatory etiology of panautonomic neuropathy in some patients.     

Murine epidermal xanthine oxidase activity: correlation with degree of hyperplasia induced by tumor promoters

Topical application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to SENCAR mouse skin results within 48 h in a 3-fold elevation of xanthine oxidase (XO) activity, an enzyme capable of generating the reactive oxygen species superoxide and hydrogen peroxide. The antiinflammatory steroid fluocinolone acetonide, an inhibitor of TPA-induced hyperplasia, as well as the multiple stages of tumor promotion as defined in SENCAR mice (Stages I and II), inhibited the TPA-dependent elevation of epidermal XO activity. Neither tosylphenylalanyl chloromethyl ketone nor retinoic acid, inhibitors of promotion Stages I and II, respectively, had significant effects on TPA-induced hyperplasia or elevated XO activity. The nonpromoting but hyperplasiogenic agents ethyl phenylpropiolate and acetic acid significantly elevated XO activity within 48 h of topical application. The non-phorbol ester tumor promoter benzoyl peroxide also elevated XO activity consistent with the degree of induced hyperplasia. Multiple treatments with TPA or ethyl phenylpropiolate resulted in a sustained elevation of XO activity which peaked at five treatments and then declined. Sustained inhibition of XO activity by p.o. administration of allopurinol did not inhibit the TPA-induced hyperplasia as determined histologically. These results suggest that the TPA-dependent elevation of epidermal XO activity is associated with the hyperplasia induced by the agent, and is a consequence of the hyperplasia rather than the cause of it.     

Characteristics of sensory trick-like manoeuvres in jaw-opening dystonia.

We evaluated the effect of different manipulations on the performance of a standardized counting task in 7 patients with idiopathic jaw-opening dystonia. Patients used a small stick as sensory stimulus. Following conditions were examined: stick placed between teeth and cheek (CHEEK), biting on stick (TEETH), voluntary jaw occlusion without stick (OCCLUSION). Articulation was rated by patients and experimenters and surface electromyographic activity (EMG) was recorded. Patient-rating (CHEEK - 36.6%, TEETH - 48.1%) and EMG (-18.1%; -17.3%) were significantly improved for conditions using the stick, whereas experimenter-rating showed a trend for TEETH (-16.2%). Although jaw occlusion during speaking deteriorates articulation in healthy subjects, there was no further deterioration in patients and EMG was even significantly reduced (-18.6%). Comparable results were obtained in 1 patient using a special dental device. We conclude that sensory tricks significantly improve subjective and objective parameters. Besides tactile stimulation, altered proprioceptive feedback and antagonist activation may modulate hyperactive dystonic networks.     

Safety of virus inactivated antithrombin III concentrate ANTITHROMBIN III IMMUNO (AT III)

In a prospective clinical trial the risk of infection after application of virus inactivated antithrombin III concentrate ANTITHROMBIN III IMMUNO (AT III) was investigated in patients undergoing cardiovascular surgery. The study was conducted according to the recommendations of the International Committee on Thrombosis and Hemostasis (ICTH), with the exception that most patients required additional blood products as well as AT III.

Twenty-seven patients were eligible to test for the risk of acquiring hepatitis B. Twenty-six patients could be evaluated in terms of hepatitis NANB transmission considering ALT-levels whereas 20 patients could be tested for anti-HCV one year after surgery. Samples from 78 patients could be monitored for anti-HIV-1. None of these patients showed any signs of infection. AT III IMMUNO seems to be an antithrombin III concentrate with low or absent infectivity.     

Cyto- and genotoxic effects of coordination complexes of platinum,palladium and rhodium in vitro

The growing industrial use of platinum group elements as catalysts, especially in automobile exhaust detoxification (trimetal catalytic converters), is causing increasing occupational and environmental pollution. The cytotoxic and mutagenic properties of industrially used coordination complexes of platinum, palladium and rhodium were investigated using the neutral red cytotoxicity assay on two established cell lines and theSalmonella typhimurium/microsome test system (Ames test). Cytotoxic effects of the platinum complexes, measured as ED₅₀, occurred at test concentrations of 0.2 mM. The analogous palladium salts tested were 3 times less toxic with ED₅₀ being 0.6 mM, while the rhodium salts proved to be 30 times less toxic (ED₅₀=6 mM). Levels of toxicity of the different complexes of a particular metal did not differ significantly from each other, which indicates that the metal itself is responsible for the toxic effects. In the Ames test, the spontaneous mutation rates increased by factors of 3 to 20 when the four tester strains were exposed to the platinum complexes. The analogous rhodium compounds proved to be considerably less mutagenic, and palladium demonstrated no mutagenic potential. As all of the four tester strains contain different mutations, the mutagenic potential of platinum and rhodium complexes appears to be based on a variety of mechanisms that damage DNA. From these in vitro experiments, it can be concluded that water-soluble complex salts of rhodium are less toxic and have a smaller mutagenic potential than the analogous platinum complexes. For palladium there is no evidence of any mutagenic property. From this point of view, the development of a catalytic converter containing predominantly palladium may be a possible means of minimizing potential health risks from this exhaust detoxification technique.     

Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2

Usher syndrome (USH) is the most frequent cause of combined deaf-blindness in man. USH is clinically and genetically heterogeneous with at least 11 chromosomal loci assigned to the three USH types (USH1A-G, USH2A-C, USH3A). Although the different USH types exhibit almost the same phenotype in human, the identified USH genes encode for proteins which belong to very different protein classes and families. We and others recently reported that the scaffold protein harmonin (USH1C-gene product) integrates all identified USH1 molecules in a USH1-protein network. Here, we investigated the relationship between the USH2 molecules and this USH1-protein network. We show a molecular interaction between the scaffold protein harmonin (USH1C) and the USH2A protein, VLGR1 (USH2C) and the candidate for USH2B, NBC3. We pinpoint these interactions to interactions between the PDZ1 domain of harmonin and the PDZ-binding motifs at the C-termini of the USH2 proteins and NBC3. We demonstrate that USH2A, VLGR1 and NBC3 are co-expressed with the USH1-protein harmonin in the synaptic terminals of both retinal photoreceptors and inner ear hair cells. In hair cells, these USH proteins are also localized in the signal uptaking stereocilia. Our data indicate that the USH2 proteins and NBC3 are further partners in the supramolecular USH-protein network in the retina and inner ear which shed new light on the function of USH2 proteins and the entire USH-protein network. These findings provide first evidence for a molecular linkage between the pathophysiology in USH1 and USH2. The organization of USH molecules in a mutual 'interactome' related to the disease can explain the common phenotype in USH.     

Erratum: Sodium channel gene (SCN5A) mutations in 44 index patients with brugada syndrome: Different incidences in familial and sporadic disease

In supplementation of previously published cardiac sodium channel (SCN5A) gene mutations that were cited in the text, in Table 2 and in Figure 2 we here apply an updated gene mutation nomenclature (Human Genome Variation Society, 2005) to facilitate mutation annotation comparison (SCN5A cDNA reference: NM_198056.1 or GI: 37622906; amino acid reference sequence: SWISS‐PROT entry Q14524, long splice variant, 2,016 amino acids): Mutation: c.2602delC Amino acid change: p.Glu868X Mutation: c.2581_2582delTT Amino acid change: p.Phe861Trp fsX90 Mutation: c.4477_4479delAAG Amino acid change: p.Lys1493del Mutation: c.5425C>A Amino acid change: p.Ser1812X