Showing papers by "University of Bonn published in 1998"

Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase.

Abstract: Peutz-Jeghers (PJ) syndrome is an autosomal-dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps and an increased risk for various neoplasms, including gastrointestinal cancer. The PJ gene was recently mapped to chromosome 19p13.3 by linkage analysis, with the highest lod score at marker D19S886. In a distance of 190 kb proximal to D19S886, we identified and characterized a novel human gene encoding the serine threonine kinase STK11. In a three-generation PJ family, we found an STK11 allele with a deletion of exons 4 and 5 and an inversion of exons 6 and 7 segregating with the disease. Sequence analysis of STK11 exons in four unrelated PJ patients has identified three nonsense and one acceptor splice site mutations. All five germline mutations are predicted to disrupt the function of the kinase domain. We conclude that germline mutations in STK11, probably in conjunction with acquired genetic defects of the second allele in somatic cells, cause the manifestations of PJ syndrome.

A Potassium Channel Mutation in Neonatal Human Epilepsy

Abstract: Benign familial neonatal convulsions (BFNC) is an autosomal dominant epilepsy of infancy, with loci mapped to human chromosomes 20q13.3 and 8q24. By positional cloning, a potassium channel gene (KCNQ2) located on 20q13.3 was isolated and found to be expressed in brain. Expression of KCNQ2 in frog (Xenopus laevis) oocytes led to potassium-selective currents that activated slowly with depolarization. In a large pedigree with BFNC, a five-base pair insertion would delete more than 300 amino acids from the KCNQ2 carboxyl terminus. Expression of the mutant channel did not yield measurable currents. Thus, impairment of potassium-dependent repolarization is likely to cause this age-specific epileptic syndrome.

Numerical integration using sparse grids

Abstract: We present new and review existing algorithms for the numerical integration of multivariate functions defined over d-dimensional cubes using several variants of the sparse grid method first introduced by Smolyak [49] In this approach, multivariate quadrature formulas are constructed using combinations of tensor products of suitable one-dimensional formulas The computing cost is almost independent of the dimension of the problem if the function under consideration has bounded mixed derivatives We suggest the usage of extended Gauss (Patterson) quadrature formulas as the one‐dimensional basis of the construction and show their superiority in comparison to previously used sparse grid approaches based on the trapezoidal, Clenshaw–Curtis and Gauss rules in several numerical experiments and applications For the computation of path integrals further improvements can be obtained by combining generalized Smolyak quadrature with the Brownian bridge construction

A Probabilistic Approach to Concurrent Mapping and Localization for Mobile Robots

Abstract: This paper addresses the problem of building large-scale geometric maps of indoor environments with mobile robots It poses the map building problem as a constrained, probabilistic maximum-likelihood estimation problem It then devises a practical algorithm for generating the most likely map from data, along with the most likely path taken by the robot Experimental results in cyclic environments of size up to 80 by 25 meter illustrate the appropriateness of the approach

The socio-economic dynamics of speculative markets: interacting agents, chaos, and the fat tails of return distributions

Abstract: This paper develops a model of the social and economic interaction of speculators in a securities or foreign exchange market. Both chartist and fundamentalist strategies are pursued by traders. The formalization of chartists behavior combines elements of mimetic contagion and trend chasing leading to waves of optimism or pessimism. Furthermore, changes of strategies from chartist to fundamentalist behavior and vice versa occur because speculators compare the performance of both strategies. The dynamic system under study encompasses the time development of the distribution of attitudes among traders as well as price adjustment. Chaotic attractors are found within a broad range of parameter values. The distributions of returns derived from chaotic trajectories of the model share important characteristics of empirical data: they exhibit high peaks around the mean as well as fat tails (leptokurtosis) and become less leptokurtotic under time aggregation.

Lantibiotics: biosynthesis and biological activities of uniquely modified peptides from gram-positive bacteria.

Abstract: A plethora of novel gene-encoded antimicrobial peptides from animals, plants and bacteria has been described during the last decade. Many of the bacterial peptides possess modified building blocks such as thioethers and thiazoles or unsaturated and stereoinverted amino acids, which are unique among ribosomally made peptides. Genetic and biochemical studies of many of these peptides, mostly the so-called lantibiotics, have revealed the degree to which cells are capable of transforming peptides by posttranslational modification. The biosynthesis follows a general scheme: Precursor peptides are first modified and then proteolytically activated; the latter may occur prior to, concomitantly with or after export from the cell. The genes for the biosynthetic machinery are organized in clusters and include information for the antibiotic prepeptide, the modification enzymes and accessory functions such as dedicated proteases and ABC transporters as well as immunity factors and regulatory proteins. These fundamental aspects are discussed along with the biotechnological potential of the peptides and of the biosynthesis enzymes, which could be used for construction of novel, peptide-based biomedical effector molecules.

SMN oligomerization defect correlates with spinal muscular atrophy severity.

Abstract: Spinal muscular atrophy (SMA) is a motor-neuron disorder resulting from anterior-horn–cell death. The autosomal recessive form has a carrier frequency of 1 in 50 and is the most common genetic cause of infant death. SMA is categorized as types I–III, ranging from severe to mild, based upon age of onset and clinical course. Two closely flanking copies of the survival motor neuron (SMN) gene are on chromosome 5q13 (ref. 1). The telomeric SMN (SMN1) copy is homozygously deleted or converted in >95% of SMA patients, while a small number of SMA disease alleles contain missense mutations within the carboxy terminus. We have identified a modular oligomerization domain within exon 6 of SMN1. All previously identified missense mutations map within or immediately adjacent to this domain. Comparison of wild-type to mutant SMN proteins of type I, II and III SMA patients showed a direct correlation between oligomerization and clinical type. Moreover, the most abundant centromeric SMN product, which encodes exons 1–6 but not 7, demonstrated reduced self-association. These findings identify decreased SMN self-association as a biochemical defect in SMA, and imply that disease severity is proportional to the intracellu-lar concentration of oligomerization-competent SMN proteins.

Can Epileptic Seizures be Predicted? Evidence from Nonlinear Time Series Analysis of Brain Electrical Activity

Abstract: We evaluate the capability of nonlinear time series analysis to extract features from brain electrical activity (EEG) predictive of epileptic seizures. Time-resolved analysis of the EEG recorded in 16 patients from within the seizure-generating area of the brain indicate marked changes in nonlinear characteristics for up to several minutes prior to seizures as compared to other states or recording sites. If interpreted as a loss of complexity in brain electrical activity these changes could reflect the hypothesized continuous increase of synchronization between pathologically discharging neurons and allow one to study seizure-generating mechanisms in humans.

An overview of the role and diversity of compatible solutes in Bacteria and Archaea

Abstract: The accumulation of compatible solutes is a prerequisite for the adaptation of microorganisms to osmotic stress imposed by salt or organic solutes Two types of strategies exist to cope with high external solute concentrations; one strategy is found in the extremely halophilic Archaea of the family Halobacteriaceae and the Bacteria of the order Haloanaerobiales involving the accumulation of inorganic ions The other strategy of osmoadaptation involves the accumulation of specific organic solutes and is found in the vast majority of microorganisms The organic osmolytes range from sugars, polyols, amino acids and their respective derivatives, ectoines and betaines The diversity of these organic solutes has increased in the past few years as more organisms, especially thermophilic and hyperthermophilic Bacteria and Archaea, have been examined The term compatible solute can also be applied to solutes that protect macromolecules and cells against stresses such as high temperature, desiccation and freezing The mechanisms by whihh compatible solutes protect enzymes, cell components and cells are still a long way from being thoroughly elucidated, but there is a growing interest in the utilization of these solutes to protect macromolecules and cells from heating, freezing and desiccation

Role of lipid-bound peptidoglycan precursors in the formation of pores by nisin, epidermin and other lantibiotics.

Abstract: It is generally assumed that type A lantibiotics primarily kill bacteria by permeabilization of the cytoplasmic membrane. As previous studies had demonstrated that nisin interacts with the membrane-bound peptidoglycan precursors lipid I and lipid II, we presumed that this interaction could play a role in the pore formation process of lantibiotics. Using a thin-layer chromatography system, we found that only nisin and epidermin, but not Pep5, can form a complex with [14C]-lipid II. Lipid II was then purified from Micrococcus luteus and incorporated into carboxyfluorescein-loaded liposomes made of phosphatidylcholine and cholesterol (1:1). Liposomes supplemented with 0.05 or 0.1 mol% of lipid II did not release any marker when treated with Pep5 or epilancin K7 (peptide concentrations of up to 5 mol% were tested). In contrast, as little as 0.01 mol% of epidermin and 0.1 mol% of nisin were sufficient to induce rapid marker release; phosphatidylglycerol-containing liposomes were even more susceptible. Controls with moenomycin-, undecaprenol- or dodecaprenolphosphate-doped liposomes demonstrated the specificity of the lantibiotics for lipid II. These results were correlated with intact cells in an in vivo model. M. luteus and Staphylococcus simulans were depleted of lipid II by preincubation with the lipopeptide ramoplanin and then tested for pore formation. When applied in concentrations below the minimal inhibitory concentration (MIC) and up to 5-10 times the MIC, the pore formation by nisin and epidermin was blocked; at higher concentrations of the lantibiotics the protective effect of ramoplanin disappeared. These results demonstrate that, in vitro and in vivo, lipid II serves as a docking molecule for nisin and epidermin, but not for Pep5 and epilancin K7, and thereby facilitates the formation of pores in the cytoplasmic membrane.

A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10.

Abstract: Obesity, a common multifactorial disorder, is a major risk factor for type 2 diabetes, hypertension and coronary heart disease1 (CHD). According to the definition of the World Health Organization (WHO), approximately 6-10% of the population in Westernized countries are considered obese2. Epidemiological studies have shown that 30-70% of the variation in body weight may be attributable to genetic factors. To date, two genome-wide scans using different obesity-related quantitative traits have provided candidate regions for obesity3,4. We have undertaken a genome-wide scan in affected sibpairs to identify chromosomal regions linked to obesity in a collection of French families. Model-free multipoint linkage analyses revealed evidence for linkage to a region on chromosome 10p (MLS=4.85). Two further loci on chromosomes 5cen–q and 2p showed suggestive evidence for linkage of serum leptin levels in a genome-wide context. The peak on chromosome 2 coincided with the region containing the gene (POMC) encoding pro-opiomelanocortin, a locus previously linked to leptin levels and fat mass in a Mexican-American population3 and shown to be mutated in obese humans5. Our results suggest that there is a major gene on chromosome 10p implicated in the development of human obesity, and the existence of two further loci influencing leptin levels.

The Lantibiotic Mersacidin Inhibits Peptidoglycan Synthesis by Targeting Lipid II

Abstract: The lantibiotic mersacidin exerts its bactericidal action by inhibition of peptidoglycan biosynthesis. It interferes with the membrane-associated transglycosylation reaction; during this step the ultimate monomeric peptidoglycan precursor, undecaprenyl-pyrophosphoryl-MurNAc-(pentapeptide)-GlcNAc (lipid II) is converted into polymeric nascent peptidoglycan. In the present study we demonstrate that the molecular basis of this inhibition is the interaction of mersacidin with lipid II. The adsorption of [14C]mersacidin to growing cells, as well as to isolated membranes capable of in vitro peptidoglycan synthesis, was strictly dependent on the availability of lipid II, and antibiotic inhibitors of lipid II formation strongly interfered with this binding. Direct evidence for the interaction was provided by studies with isolated lipid II. [14C]mersacidin associated tightly with [14C]lipid II micelles; the complex was stable even in the presence of 1% sodium dodecyl sulfate. Furthermore, the addition of isolated lipid II to the culture broth efficiently antagonized the bactericidal activity of mersacidin. In contrast to the glycopeptide antibiotics, complex formation does not involve the C-terminal D-alanyl-D-alanine moiety of the lipid intermediate. Thus, the interaction of mersacidin with lipid II apparently occurs via a binding site which is not targeted by any antibiotic currently in use.

Axiomatic Characterization of the Quadratic Scoring Rule

Abstract: In the evaluation of experiments often the problem arises of how to compare the predictive success of competing probabilistic theories. The quadratic scoring rule can be used for this purpose. Originally, this rule was proposed as an incentive compatible elicitation method for probabilistic expert judgments. It is shown that up to a positive linear transformation, the quadratic scoring rule is characterized by four desirable properties.

PTEN mutations in gliomas and glioneuronal tumors

Abstract: Cytogenetic and loss of heterozygosity studies have suggested the presence of at least one tumor suppressor gene on chromosome 10 involved in the formation of high grade gliomas. Recently, the PTEN gene, also termed MMAC1 or TEP1, on chromosomal band 10q23 has been identified. Initial studies revealed mutations of PTEN in limited series of glioma cell lines and glioblastomas. In order to systematically evaluate the involvement of PTEN in gliomas, we have analysed the entire PTEN coding sequence by SSCP and direct sequencing in a series of 331 gliomas and glioneuronal tumors. PTEN mutations were detected in 20/142 glioblastomas, 1/7 giant cell glioblastomas, 1/2 gliosarcomas, 1/30 pilocytic astrocytomas and 2/22 oligodendrogliomas. No PTEN mutations were detected in 52 astrocytomas, 37 oligoastrocytomas, three subependymal giant cell astrocytomas, four pleomorphic xanthoastrocytomas, 15 ependymomas, 16 gangliogliomas and one dysembryoplastic neuroepithelial tumor. In addition, all tumors were examined for the presence of homozygous deletions of the PTEN gene; these were detected in 7 glioblastomas that did not have PTEN mutations. Therefore, PTEN mutations occur in approximately 20% of glioblastomas but are rare in lower grade gliomas. These findings confirm that PTEN is one of the chromosome 10 tumor suppressor genes involved in the development of glioblastomas.

The ErbB2 and ErbB3 receptors and their ligand, neuregulin-1, are essential for development of the sympathetic nervous system

Abstract: Neuregulins (NDF, heregulin, GGF ARIA, or SMDF) are EGF-like growth and differentiation factors that signal through tyrosine kinase receptors of the ErbB family. Here, we report a novel phenotype in mice with targeted mutations in the erbB2, erbB3, or neuregulin-1 genes. These three mutations cause a severe hypoplasia of the primary sympathetic ganglion chain. We provide evidence that migration of neural crest cells to the mesenchyme lateral of the dorsal aorta, in which they differentiate into sympathetic neurons, depends on neuregulin-1 and its receptors. Neuregulin-1 is expressed at the origin of neural crest cells. Moreover, a tight link between neuregulin-1 expression, the migratory path, and the target site of sympathogenic neural crest cells is observed. Sympathetic ganglia synthesize catecholamines in the embryo and the adult. Accordingly, catecholamine levels in mutant embryos are severely decreased, and we suggest that the lack of catecholamines contributes to the embryonal lethality of the erbB3 mutant mice. Thus, neuregulin-1, erbB2, and erbB3 are required for the formation of the sympathetic nervous system; the block in development observed in mutant mice is caused by a lack of neural crest precursor cells in the anlage of the primary sympathetic ganglion chain. Together with previous observations, these findings establish the neuregulin signaling system as a key regulator in the development of neural crest cells.

Chimeric brains generated by intraventricular transplantation of fetal human brain cells into embryonic rats

Abstract: Limited experimental access to the central nervous system (CNS) is a key problem in the study of human neural development, disease, and regeneration. We have addressed this problem by generating neural chimeras composed of human and rodent cells. Fetal human brain cells implanted into the cerebral ventricles of embryonic rats incorporate individually into all major compartments of the brain, generating widespread CNS chimerism. The human cells differentiate into neurons, astrocytes, and oligodendrocytes, which populate the host fore-, mid-, and hindbrain. These chimeras provide a unique model to study human neural cell migration and differentiation in a functional nervous system.

Connexin32‐null mice develop demyelinating peripheral neuropathy

Abstract: Mutations in the gene encoding the gap junction protein connexin32 (Cx32) cause X-linked Charcot-Marie-Tooth disease (CMTX), a common form of inherited demyelinating peripheral neuropathy. To learn more about the pathogenesis of CMTX, we examined the PNS and CNS of cx32-null mice (cx32-/Y males and cx32-/-females) by light and electron microscopy. These mice develop a progressive demyelinating peripheral neuropathy beginning by 3 months of age, and at all ages, motor fibers are more affected than sensory fibers. Like other genes of the X chromosome, the cx32 gene appears to be randomly inactivated, since only some myelinating Schwann cells express Cx32 in heterozygous cx32 +/- females. Heterozygous cx32 +/- females have fewer demyelinated and remyelinated axons than age-matched homozygous cx32-/- females and cx32-/Y males. Although oligodendrocytes also express Cx32, no abnormalities in CNS myelin were found. These findings indicate that a null cx32 allele in myelinating Schwann cells is sufficient to cause an inherited demyelinating neuropathy, so that Cx32 has an essential role in myelinating Schwann cells both in mice and in humans.

Measurements of the Proton and Deuteron Spin Structure Functions g1 and g2

Abstract: Measurements are reported of the proton and deuteron spin structure functions ${g}_{1}^{p}$ and ${g}_{1}^{d}$ at beam energies of 29.1, 16.2, and 9.7 GeV, and ${g}_{2}^{p}$ and ${g}_{2}^{d}$ at a beam energy of 29.1 GeV. The integrals ${\ensuremath{\Gamma}}_{p}={\ensuremath{\int}}_{0}^{1}{g}_{1}^{p}{(x,Q}^{2})dx$ and ${\ensuremath{\Gamma}}_{d}={\ensuremath{\int}}_{0}^{1}{g}_{1}^{d}{(x,Q}^{2})dx$ were evaluated at fixed ${Q}^{2}=3(\mathrm{GeV}{/c)}^{2}$ using the full data set to yield ${\ensuremath{\Gamma}}_{p}=0.132\ifmmode\pm\else\textpm\fi{}0.003(\mathrm{stat})\ifmmode\pm\else\textpm\fi{}0.009(\mathrm{syst})$ and ${\ensuremath{\Gamma}}_{d}=0.047\ifmmode\pm\else\textpm\fi{}0.003\ifmmode\pm\else\textpm\fi{}0.006.$ The ${Q}^{2}$ dependence of the ratio ${g}_{1}{/F}_{1}$ was studied and found to be small for ${Q}^{2}g1(\mathrm{GeV}{/c)}^{2}.$ Within experimental precision the ${g}_{2}$ data are well described by the twist-2 contribution, ${g}_{2}^{\mathrm{WW}}.$ Twist-3 matrix elements were extracted and compared to theoretical predictions. The asymmetry ${A}_{2}$ was measured and found to be significantly smaller than the positivity limit $\sqrt{R}$ for both proton and deuteron targets. ${A}_{2}^{p}$ is found to be positive and inconsistent with zero. Measurements of ${g}_{1}$ in the resonance region show strong variations with $x$ and ${Q}^{2},$ consistent with resonant amplitudes extracted from unpolarized data. These data allow us to study the ${Q}^{2}$ dependence of the integrals ${\ensuremath{\Gamma}}_{p}$ and ${\ensuremath{\Gamma}}_{n}$ below the scaling region.

Theoretical analysis of electronic delocalization

Abstract: A block-localized wave function method is introduced to evaluate the electronic delocalization effect in molecules. The wave function for the hypothetical and strictly localized structure is constructed based on the assumption that all electrons and primitive basis functions can be divided into several subgroups; each localized molecular orbital is expanded in terms of primitive orbitals belonging to only one subgroup. The molecular orbitals belonging to the same subgroup are constrained to be mutually orthogonal, while those belonging to different subgroups are free to overlap. The final block-localized wave function at the Hartree–Fock level is expressed by a Slater determinant. In this manner, the energy difference between the Hartree–Fock wave function and the block-localized wave function can be generally defined as the electronic delocalization energy. The method is applied to two cases. The first concerns the resonance stabilization in the allyl ions. We find that the vertical resonance energies fo...

Transplacental uptake of glucose is decreased in embryonic lethal connexin26-deficient mice.

Abstract: Mice that harbor a targeted homozygous defect in the gene coding for the gap junctional protein connexin26 died in utero during the transient phase from early to midgestation. From day 10 post coitum onwards, development of homozygous embryos was retarded, which led to death around day 11 post coitum. Except for growth retardation, no gross morphological alterations were detected between homozygous connexin26-defective embryos and wild-type littermates. At day 9 postcoitum, when chorioallantoic placenta started to function, connexin26 was weakly expressed in the yolk sac epithelium, between syncytiotrophoblasts I and II in the labyrinth region of the placenta, and in the skin of the embryo. At day 10 post coitum, expression of connexin26 in the placenta was much stronger than at the other locations. To analyze involvement of connexin26 in the placental transfer of nutrients, we have measured embryonic uptake of the nonmetabolizable glucose analogue 3-O-[14C]methylglucose, injected into the maternal tail vein. At day 10 post coitum, viable, homozygous connexin26-defective embryos accumulated only approximately 40% of the radioactivity measured in wild-type and heterozygous littermates of the same size. We conclude that the uptake of glucose, and presumably other nutrients as well, from maternal blood into connexin26-deficient mouse embryos was severely impaired and apparently not sufficient to support the rapid organogenesis during midgestation. Our results suggest that connexin26 gap junction channels likely fulfill an essential role in the transfer of maternal nutrients and embryonic waste products between syncytiotrophoblast I and II in the labyrinth layer of the mouse placenta.

Successful Verbal Encoding into Episodic Memory Engages the Posterior Hippocampus: A Parametrically Analyzed Functional Magnetic Resonance Imaging Study

Abstract: The medial temporal lobe (MTL) is essential for episodic memory encoding, as evidenced by memory deficits in patients with MTL damage. However, previous functional neuroimaging studies have either failed to show MTL activation during encoding or they did not differentiate between two MTL related processes: novelty assessment and episodic memory encoding. Furthermore, there is evidence that the MTL can be subdivided into subcomponents serving different memory processes, but the extent of this functional subdivision remains unknown. The aim of the present functional magnetic resonance imaging (fMRI) study was to investigate the role of the MTL in episodic encoding and to determine whether this function might be restricted to anatomical subdivisions of the MTL. Thirteen healthy volunteers performed a word list learning paradigm with free recall after distraction. Functional images acquired during encoding were analyzed separately for each participant by a voxel-wise correlation (Kendall's tau) between the time series of the T2*-signal intensity and the number of subsequently recalled words encoded during each particular scan. Of the 13 participants, 11 showed voxel clusters with statistically significant, positive correlations in the posterior part of the hippocampus. Across participants, an ANOVA on the number of voxels with significant, positive correlations within individually defined volumes of interest confirmed a statistically significant difference in activation for anterior versus posterior regions of the hippocampus. However, no differences between left and right hippocampal activation were revealed. Thus, these findings demonstrate that successful encoding into episodic memory engages neural circuits in the posterior part of the hippocampus.

Local and global vectors in desert ant navigation

Abstract: Desert ants returning from a foraging trip to their nest navigate both by path integration and by visual landmarks1, 2, 3. In path integration, ants compute their net distance and direction from the nest throughout their outward1 and return4 journeys, and so can always return directly home from their current location1. As the path-integration vector is updated over the entire journey, we call it a global vector. On a familiar route, when ants can steer by visual landmarks, they adopt a fixed and often circuitous path consisting of several separate segments that point in different directions2,3,5. Here we show that, as in honeybees6, 7, 8, such multisegment journeys are composed partly of stored local movement vectors, which are associated with landmarks and are recalled at the appropriate place. We also show that a local vector learnt at one value of the global vector can be recalled at many values, and that expression of the global vector is temporarily inhibited while the local vector is used. These results indicate that the global vector is ignored during navigation through familiar, cluttered territory, but that it re-emerges to take the ant home once the insect leaves the clutter and other guidance strategies cease to operate.

Changes in platelet size and count in unstable angina compared to stable angina or non-cardiac chest pain

Abstract: Aims An increase in platelet aggregability is associated with unstable angina and myocardial infarction. Platelet size and activity correlate and mean platelet volume was found to be increased before acute myocardial infarction. We measured the mean platelet volume and platelet count in patients with stable angina, unstable angina and non-cardiac chest pain. Methods and results We studied 981 patients (734 men; 247 women) defined clinically as stable angina (n=688), unstable angina (n=108) and unstable angina requiring immediate angioplasty (n=52). After coronary angiography the patients were subdivided into single (n=269), double (n=304) and triple-vessel disease (n=311) and the control group of non-cardiac chest pain (n=97). There was no significant difference in platelet count between the control group and patients with 1, 2, or 3-vessel disease. However, the platelet size in patients with coronary artery disease was significantly larger (single: 8·7±1·19fl; double: 8·7±1·12fl; triple-vessel disease: 8·8±1·18fl) than the control group (8·2±0·95fl) ( P <0·01). Patients with stable angina similarly had no significant difference in platelet count compared to the control group but did have a significantly increased mean platelet volume (8·7±1·13; P <0·01). In contrast, patients with unstable angina had a decreased platelet count (245±56×10/l) compared to either stable angina (262±62×10/l; P <0·05) or the control group (261±58×10/l; P <0·05); furthermore, the mean platelet volume (9·4±1·23fl) was significantly greater than for stable angina ( P <0·01). Patients with unstable angina requiring immediate PTCA had an even lower platelet count (231±55×10/l) and higher mean platelet volume (10·4±1·03fl) ( P <0·01) than the rest of the population with unstable angina. Conclusions In stable angina the platelet count is unchanged compared to patients with normal coronary arteries but the platelet size is increased. However, in unstable angina there is a decrease in platelet count and an even larger increase in platelet size. We interpret this as meaning that unstable angina might be associated or preceded by an increase in platelet destruction rate that is not completely compensated for by an increase in platelet production rate. The large, more reactive platelets might be causally related to an ongoing coronary artery obstruction in unstable angina.

Atrioverter: An Implantable Device for the Treatment of Atrial Fibrillation

Abstract: Background: During atrial fibrillation, electrophysiological changes occur in atrial tissue that favor the maintenance of the arrhythmia and facilitate recurrence after conversion to sinus rhythm. An implantable defibrillator connected to right atrial and coronary sinus defibrillation leads allows prompt restoration of sinus rhythm by a low-energy shock. The safety and efficacy of this system, called the Atrioverter, were evaluated in a prospective, multicenter study. Methods and results: The study included 51 patients with recurrent atrial fibrillation who had not responded to antiarrhythmic drugs, were in New York Heart Association Heart failure class I or II, and were at low risk for ventricular arrhythmias. The atrial defibrillation threshold had to be ≤ 240 V during preimplant testing. Atrial fibrillation detection, R-wave shock synchronization, and defibrillation threshold were tested at implantation and during follow-up. Shock termination of spontaneous episodes of atrial fibrillation was performed under physician observation. Results are given after a minimum of 3 months of follow-up. During a follow-up of 72 to 613 days (mean, 259 ± 138 days), 96% of 227 spontaneous episodes of atrial fibrillation in 41 patients were successfully converted to sinus rhythm by the Atrioverter. In 27% of episodes, several shocks were required because of early recurrence of atrial fibrillation. Shocks did not induce ventricular arrhythmias. Most patients received antiarrhythmic medication during follow-up. In 4 patients, the Atrioverter was removed: in 1 because of infection, in 1 because of cardiac tamponade, and in 1 because of frequent episodes of atrial fibrillation requiring His bundle ablation. Conclusions: With the Atrioverter, prompt and safe restoration of sinus rhythm is possible in patients with recurrent atrial fibrillation.