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Thomas Mayer

Publications and source records attributed to Thomas Mayer.

At least 19 recordsLinked to original sources
PubMed2006

Seizure anticipation by patients with focal and generalized epilepsy: a multicentre assessment of premonitory symptoms.

PURPOSE: To assess subjective seizure anticipation in patients with focal and generalized epilepsy. METHODS: Five hundred consecutively recruited out-patients (251 male, 249 female, mean age 38.1 year) from three German tertiary epilepsy referral centres filled out questionnaires regarding subjective anticipation of seizures by at least 30 min and to timing and semiologic characteristics of their premonitory symptoms versus those of ictal phenomena. Patients were not regarded as having prodromi if the semiology of symptoms reported long before a seizure was identical to auras. RESULTS: 6.2% of patients reported that they were able to anticipate seizures. Premonitory symptoms were classified as stereotyped in all but one patient. An intraindividual semiologic analysis showed that the majority of these patients had symptoms, which were distinct from ictal experiences during auras. Seizure anticipation was reported both by patients with focal and idiopathic generalized epilepsy. The median estimated time interval between occurrence of premonitory symptoms and seizure onset was 90 min. CONCLUSIONS: This study gives evidence that both patients with focal and idiopathic generalized epilepsy may subjectively anticipate the occurrence of epileptic seizures. Premonitory symptoms are distinct from auras in terms of semiology and time of occurrence. The lower percentage of patients regarded as having premonitory symptoms as compared to some earlier reports may be related to stricter criteria and to the exclusion of auras, which could directly evolve into seizures, and other ictal events. Premonitory symptoms occur at similar periods prior to seizures as anticipatory EEG-changes have been reported using methods from time series analysis.

Adult↗
PubMed2006

Synchrotron photoemission analysis of semiconductor/electrolyte interfaces by the frozen-electrolyte approach: interaction of HCl in 2-propanol with GaAs(100).

Perspectives of a new approach for the synchrotron photoemission spectroscopic analysis of chemical processes at solid/liquid interfaces under UHV conditions have been explored. A thin layer of HCl-2-propanol solution was frozen-in on the semiconductor GaAs(100) wafer surface by cooling the substrate to liquid nitrogen temperature after etching off the native oxide layer under N2 atmosphere. Chemical reactions induced in situ by exposure to synchrotron radiation (SR) and by stepwise heating have been monitored. Right after etching and freezing, the surface is covered by gallium chlorides with 1, 2, 3, and 4 Cl ions attached and lattice back-bonded to As atoms, as well as by elemental arsenic As0 and 2-propanol. Exposure to SR at low temperature produces surface As chlorides at the expense of As0. The GaCl3 and GaCl2 emissions diminish while GaCl is enhanced. On the other hand, heating the sample to approximately 130 K just above H2O desorption causes the thermodynamically expected reaction of AsCl3 with the substrate GaAs to form Ga chloride species and As0. Heating the sample to room temperature leaves only As0 on the surface and for gallium the content of all surface chlorides is drastically reduced. By further heating to 400 K elemental arsenic starts to desorb and the Ga chloride surface content is reduced. Using different excitation energies the depth composition of the reaction products has been monitored indicating a tendency of decreasing chlorination numbers and increasing Ga vs As chloride content toward the pristine substrate at each stage of the reaction.

Journal Article↗
PubMed2006

Restless legs syndrome: epidemiological and clinicogenetic study in a South Tyrolean population isolate.

Genetic contributions to restless legs syndrome (RLS) have been consistently recognized from population and family studies. To determine the clinical and genetic features of RLS in a population isolate and explore linkage to three previously described susceptibility loci on chromosomes 12q, 14q, and 9p, respectively, an isolated population in the South Tyrolean Alps was identified and 530 adults participated in the study. Using a two-step strategy, 47 patients with idiopathic RLS were ascertained. The prevalence in the population was 8.9%. Twenty-eight patients (59.6%) had at least one affected first-degree relative and were classified as hereditary cases. In a single extended pedigree, linkage to known RLS loci was investigated specifying autosomal dominant and recessive models; parametric and nonparametric multipoint linkage scores were computed. None of the calculated linkage scores was suggestive of linkage between RLS and any of the three investigated loci. This study was conducted in a population isolate providing for a homogeneous genetic and environmental background. The absence of a suggestive linkage signal at the three known RLS susceptibility loci is indicative of further locus heterogeneity of this frequent disorder and encourages further studies to unveil the genetic causes of RLS.

Adult↗
PubMed2006

Cell-based assays using primary endothelial cells to study multiple steps in inflammation.

Cell-based assays are powerful tools for drug discovery and provide insight into complex signal transduction pathways in higher eukaryotic cells. Information gleaned from assays that monitor a cellular phenotype can be used to elucidate the details of a single pathway and to establish patterns of cross talk between pathways. By selecting the appropriate cell model, cell-based assays can be used to understand the function of a specific cell type in a complex disease process such as inflammation. We have used human umbilical vein endothelial cells to establish three cell-based, phenotypic assays that query different stages of a major signaling pathway activated in inflammation. One assay analyzes the tumor necrosis factor alpha (TNFalpha)-induced translocation of the transcription factor NF-kappaB from the cytoplasm into the nucleus 20 min after stimulation with TNFalpha. Two more assays monitor the expression of E-selectin and VCAM-1, 4 and 24 h after stimulation with TNFalpha. Indirect immunofluorescence and high-throughput automated microscopy were used to analyze cells. Imaging was performed with the IN Cell Analyzer 3000. All assays proved to be highly robust. Z' values between 0.7 and 0.8 make each of the three assays well suited for use in high-throughput screening for drug or probe discovery.

Animals↗
PubMed2005

Temporary aneurysm orifice balloon occlusion as an alternative to retrograde suction decompression for giant paraclinoid internal carotid artery aneurysms: technical note.

OBJECTIVE: Giant paraclinoid carotid artery aneurysms frequently require the temporary interruption of local circulation to facilitate safe clip occlusion. Owing to the brisk retrograde blood flow through the ophthalmic artery and cavernous branches, the simple trapping of the aneurysm by cervical internal carotid artery clamping and intracranial distal clipping may not adequately soften the lesion. Retrograde suction decompression aspiration of this collateral supply by a catheter introduced into the cervical internal carotid artery is a popular method to achieve aneurysm deflation. With a large collateral supply, the method is not effective enough. The advent of relatively long and maneuverable soft balloons allows temporary occlusion of the aneurysm orifice. METHODS: We applied this method in two instances of giant carotid ophthalmic aneurysms. In both instances, a 15- to 20-mm-long and 4-mm-wide occlusion balloon was inserted in the internal carotid artery at the level of the aneurysm before craniotomy. After craniotomy and dissection of the aneurysm neck, the balloon was inflated under intraoperative angiographic control. RESULTS: The aneurysm became soft enough in both cases without tapping and aspiration to allow safe clip occlusion. In the first case, the postoperative course was uneventful and visual acuity improved. A known additional infraclinoid part of the aneurysm was eliminated endovascularly 5 months later using balloon-protected injection of vinyl alcohol copolymer (Onyx; Micro Therapeutics, Inc., Irvine, CA). In the second case, a postoperative symptomatic vasospasm developed 15 hours after surgery. Hypertensive therapy resulted in the disappearance of symptoms and an otherwise uneventful course with improvement of vision. CONCLUSION: This preliminary experience suggests that this new method is a feasible alternative to retrograde suction decompression.

Balloon Occlusion↗
PubMed2005

Sequence characteristics of functional siRNAs.

RNA interference in mammalian cells is actively used to conduct genetic screens, to identify and to validate targets, and to elucidate regulators and modifiers of cellular pathways. To ensure the specificity and efficacy of the active 21mer siRNA molecules, it is pertinent to develop a strategy for their rational design. Here we show that most functional siRNAs have characteristic sequence features. We tested 601 siRNAs targeting one exogenous and three endogenous genes. The efficacy of the siRNAs was determined at the protein level. Using a decision tree algorithm in combination with information analysis, our analyses revealed four sets of rules with a mean knockdown efficacy ranging from 60% to 73%. (To distinguish between percentages used to describe the quality of an siRNA and the percentages used to describe parts of data sets we underlined the former throughout this paper.) The best rule comprises an A/U at positions 10 and 19, a G/C at position 1, and more than three A/Us between positions 13 and 19, in the sense strand of the siRNA sequence. Using these rules, there is a 99.9% chance of designing an effective siRNA in a set of three with more than 50% knockdown efficiency in a biological readout.

Base Sequence↗
PubMed2004

Macrocephalic mental retardation associated with a novel C-terminal MECP2 frameshift deletion.

UNLABELLED: We report a novel C-terminal MECP2 frameshift deletion (1135_1142delCCCGTG CC) in a 19-year-old woman with mental retardation and epilepsy. Preservation of language capabilities, purposeful hand use and sufficient locomotion implied an atypical variant of Rett syndrome (OMIM 312750). Occipito-frontal head circumference was large at birth (36 cm; SDS 1.7) and increased until adulthood (58.5 cm; SDS 2.3). CONCLUSION: Our observation indicates that head size and head growth are of limited reliability in the diagnosis of MECP2-associated phenotypes.

Adult↗
PubMed2004

FTY720 and cyclosporine: evaluation for a pharmacokinetic interaction.

BACKGROUND: FTY720 is a sphingosine-1-phosphate receptor agonist intended for use in immunoprophylaxis regimens to prevent acute rejection after organ transplantation. OBJECTIVE: To evaluate the potential for a pharmacokinetic drug interaction between the immunomodulator FTY720 and cyclosporine to support the use of this drug combination in organ transplantation. METHODS: In this open-label, randomized crossover study, 12 subjects with psoriasis received a single dose of FTY720 1 mg alone and on day 5 of an 8-day course of cyclosporine 200 mg twice daily. The single-dose pharmacokinetics of FTY720 and the steady-state pharmacokinetics of cyclosporine were characterized when given alone and during coadministration. Routine safety data were collected, with special attention to total blood lymphocyte counts and heart rate. RESULTS: Cyclosporine coadministration compared with FTY720 given alone did not significantly alter FTY720 maximum concentration (C(max)) (0.57 +/- 0.17 vs 0.58 +/- 0.19. ng/mL, respectively) or AUC(0-t) (41 +/- 13 vs 41 +/- 13 ng. h/mL, respectively). Likewise for cyclosporine, FTY720 coadministration did not alter the steady-state Cmax compared with cyclosporine given alone (1452 +/- 308 vs 1376 +/- 149 ng/mL, respectively) or AUC(tau) (6385 +/- 1578 vs 6031 +/- 1051 ng. h/mL, respectively). Mean lymphocyte counts decreased from baseline by an average of 35% over the first 2 days after FTY720 administration and thereafter increased to prestudy values by day 5 similarly in the absence and presence of cyclosporine. The morning mean supine heart rate decreased approximately 10% and returned to prestudy rates by day 5 after administration of FTY720 alone and with cyclosporine. Heart rate changes were asymptomatic in all study participants. One subject experienced asymptomatic second-degree type 1 atrioventricular (Wenckebach) block. CONCLUSIONS: The pharmacokinetics of single-dose FTY720 and steady-state cyclosporine were not altered during coadministration.

Adult↗
PubMed2004

Synthesis and target identification of hymenialdisine analogs.

Hymenialdisine (HMD) is a sponge-derived natural product kinase inhibitor with nanomolar activity against CDKs, Mek1, GSK3beta, and CK1 and micromolar activity against Chk1. In order to explore the broader application of the pyrrolo[2,3-c]azepine skeleton of HMD as a general kinase inhibitory scaffold, we searched for additional protein targets using affinity chromatography in conjunction with the synthesis of diverse HMD analogs and profiled HMD against a panel of 60 recombinant enzymes. This effort has led to nanomolar to micromolar inhibitors of 11 new targets including p90RSK, KDR, c-Kit, Fes, MAPK1, PAK2, PDK1, PKCtheta, PKD2, Rsk1, and SGK. The synthesis of HMD analogs has resulted in the identification of compounds with enhanced and/or dramatically altered selectivities relative to HMD (28n) and in molecules with antiproliferative activities 30-fold higher than HMD (28p).

Amino Acid Sequence↗
PubMed2004

Extramedullary hematopoiesis occurring as a nasal polyp in a man with a myeloproliferative disorder.

We describe the case of a patient with a known myeloproliferative disorder who presented with epistaxis and what clinically appeared to be a nasal polyp. The mass was resected and proved to represent a focus of extramedullary hematopoiesis. The patient subsequently developed extramedullary hematopoiesis of the skin and the stomach wall. Following nasal polypectomy, he did well for a time, but he eventually died as a result of other complications of his disease. This unique case serves as a reminder that common rhinologic complaints can be a sign of significant and life-threatening pathology.

Aged↗
PubMed2003

Fusion of cells by flipped SNAREs.

The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) hypothesis suggests that pairs of proteins known as vesicle (v-) SNAREs and target membrane (t-) SNAREs interact specifically to control and mediate intracellular membrane fusion events. Here, cells expressing the interacting domains of v- and t-SNAREs on the cell surface were found to fuse spontaneously, demonstrating that SNAREs are sufficient to fuse biological membranes.

Animals↗
PubMed2003

Letter of apology.

Explore the source record for details and available documents.

Basilar Artery↗
PubMed2003

Pharmacodynamics of single doses of the novel immunosuppressant FTY720 in stable renal transplant patients.

FTY720, a new and potent immunosuppressant, causes in animal models a rapid, reversible reduction of all subsets of peripheral blood lymphocytes, inducing their migration to secondary lymphoid organs. In this human phase I trial, the pharmacodynamics of single oral doses of FTY720 were evaluated. A randomized, double-blind, placebo-controlled, time-lagged study of six different single ascending oral doses of FTY720 ranging from 0.25 to 3.5 mg was conducted in stable renal transplant patients receiving a cyclosporine-based regimen. Absolute and subset lymphocyte counts, as well as absolute differential leukocyte counts, were determined by differential blood counts and flow cytometry at screening and multiple intervals thereafter. A pharmacodynamic model was established. Twenty-four single doses of FTY720 that were administered caused a transient, reversible pan-lymphopenia within 4 h. Lymphocyte subgroup analysis revealed that almost all subsets declined, with CD4- and CD45RA-positive cells being affected the most. Natural killer cells, granulocytes and monocytes were not influenced by FTY720. The lymphocyte count returned to baseline within 72 h in all dosing cohorts except the highest. Pharmacokinetik/pharmacodynamic modelling revealed a nonlinear dose effect and resulted in a good fit with observed values. These data show that FTY720 is highly effective in humans, with single oral doses of FTY720 ranging from 0.25 to 3.5 mg causing a reversible selective panlymphopenia.

Fingolimod Hydrochloride↗
PubMed2002

Pre- rather than co-application of vigabatrin increases the efficacy of tiagabine in hippocampal slices.

PURPOSE: The antiepileptic drug vigabatrin (VGB) increases intracellular availability of the inhibitory transmitter gamma-aminobutyric acid (GABA) by inhibition of GABA-transaminase. A blockade of the GABA uptake is the main mechanism of action of tiagabine (TGB). Based on this, the two antiepileptic drugs (AEDs) can be speculated to act synergistically so that their combined antiepileptic efficacy is supraadditive. METHODS: To test this, experiments were performed on hippocampal slices of guinea-pigs. As an epilepsy model, epileptiform field potentials (EFPs) were induced by omission of Mg2+ from the bath solution and recorded in stratum pyramidale of the CA3 region. VGB (7.5 microM) and TGB (0.75 microM) were added to the superfusate. RESULTS: VGB, given alone, failed to decrease the repetition rate of EFPs. Similarly, TGB applied alone only transiently led to a nonsignificant reduction of the EFP frequency. Combining VGB and TGB, their suppressive efficacy increased, yielding a significant reduction of EFP frequency, which, however, again did not persist. Pretreatment of the preparations with VGB for 2 h, followed by additional application of TGB, or TGB alone, drastically and persistently potentiated the effects. CONCLUSIONS: These results demonstrate that VGB and TGB show favorable pharmacodynamic interactions, provided VGB is allowed to block intracellular GABA degradation before GABA uptake block by TGB.

Animals↗