Successful Non-Invasive treatment of stricturing fibrosing colonopathy in an adult patient

<p>Abstract</p> <p>Objective</p> <p>Fibrosing colonopathy (FC) is a rare entity associated with cystic fibrosis (CF). Until now, patients with stricturing FC have usually been treated surgically. In this instance, we aimed at avoiding surgery by applying a new conservative approach.</p> <p>Methods</p> <p>Case report on an adult with CF who developed persistent abdominal pain due to a non-passable stricture in the right transverse colon. Histology confirmed fibrosing colonopathy.</p> <p>Results</p> <p>Initially we treated the patient with prednisolone pulse therapy and additive antibiotic therapy. For maintenance therapy we administered budesonide. The patient underwent clinical, laboratory and endoscopic follow-up over a three-year period. The stricture healed and was easy to pass. A relapse in the cecum at the ileocecal valve again improved under steroid and antibiotic therapy.</p> <p>Conclusions</p> <p>We present a novel therapeutic approach for advanced stricturing FC in an adult patient which successfully avoided surgery (right hemicolectomy) over a three year follow up.</p

Phonon Assisted Multimagnon Optical Absorption and Long Lived Two-Magnon States in Undoped Lamellar Copper Oxides

We calculate the effective charge for multimagnon infrared (IR) absorption assisted by phonons in the parent insulating compounds of cuprate superconductors and the spectra for two-magnon absorption using interacting spin-wave theory. Recent measured bands in the mid IR [Perkins et al. Phys. Rev. Lett. {\bf 71} 1621 (1993)] are interpreted as involving one phonon plus a two-magnon virtual bound state, and one phonon plus higher multimagnon absorption processes. The virtual bound state consists of a narrow resonance occurring when the magnon pair has total momentum close to $(\pi,0)$.Comment: 4 page

Role of Van Hove Singularities and Momentum Space Structure in High-Temperature Superconductivity

There is a great deal of interest in attributing the high critical temperatures of the cuprates to either the proximity of the Fermi level to a van Hove singularity or to structure of the superconducting pairing potential in momentum space far from the Fermi surface. We examine these ideas by calculating the critical temperature Tc for model Einstein-phonon- and spin-fluctuation-mediated superconductors within both the standard, Fermi-surface-restricted Eliashberg theory and the exact mean field theory, which accounts for the full momentum structure of the pairing potential and the energy dependence of the density of states. By using two models of spin-fluctuation-mediated pairing in the cuprates, we demonstrate that our results are independent of the details of the dynamical susceptibility, which is taken to be the pairing potential. We also compare these two models against available neutron scattering data, since these data provide the most direct constraints on the susceptibility. We conclude that the van Hove singularity does not drastically alter Tc from its value when the density of states is constant and that the effect of momentum structure is significant but secondary in importance to that of the energy dependence in the density of states.Comment: 23 pages, 6 figures upon request, revtex version 2, vHs-

The Electron-Phonon Interaction in the Presence of Strong Correlations

We investigate the effect of strong electron-electron repulsion on the electron-phonon interaction from a Fermi-liquid point of view: the strong interaction is responsible for vertex corrections, which are strongly dependent on the $v_Fq/\omega$ ratio. These corrections generically lead to a strong suppression of the effective coupling between quasiparticles mediated by a single phonon exchange in the $v_Fq/\omega \gg 1$ limit. However, such effect is not present when $v_Fq/\omega \ll 1$. Analyzing the Landau stability criterion, we show that a sizable electron-phonon interaction can push the system towards a phase-separation instability. A detailed analysis is then carried out using a slave-boson approach for the infinite-U three-band Hubbard model. In the presence of a coupling between the local hole density and a dispersionless optical phonon, we explicitly confirm the strong dependence of the hole-phonon coupling on the transferred momentum versus frequency ratio. We also find that the exchange of phonons leads to an unstable phase with negative compressibility already at small values of the bare hole-phonon coupling. Close to the unstable region, we detect Cooper instabilities both in s- and d-wave channels supporting a possible connection between phase separation and superconductivity in strongly correlated systems.Comment: LateX 3.14, 04.11.1994 Preprint no.101

Segment-Wise Genome-Wide Association Analysis Identifies a Candidate Region Associated with Schizophrenia in Three Independent Samples

Recent studies suggest that variation in complex disorders (e.g., schizophrenia) is explained by a large number of genetic variants with small effect size (Odds Ratio∼1.05–1.1). The statistical power to detect these genetic variants in Genome Wide Association (GWA) studies with large numbers of cases and controls (∼15,000) is still low. As it will be difficult to further increase sample size, we decided to explore an alternative method for analyzing GWA data in a study of schizophrenia, dramatically reducing the number of statistical tests. The underlying hypothesis was that at least some of the genetic variants related to a common outcome are collocated in segments of chromosomes at a wider scale than single genes. Our approach was therefore to study the association between relatively large segments of DNA and disease status. An association test was performed for each SNP and the number of nominally significant tests in a segment was counted. We then performed a permutation-based binomial test to determine whether this region contained significantly more nominally significant SNPs than expected under the null hypothesis of no association, taking linkage into account. Genome Wide Association data of three independent schizophrenia case/control cohorts with European ancestry (Dutch, German, and US) using segments of DNA with variable length (2 to 32 Mbp) was analyzed. Using this approach we identified a region at chromosome 5q23.3-q31.3 (128–160 Mbp) that was significantly enriched with nominally associated SNPs in three independent case-control samples. We conclude that considering relatively wide segments of chromosomes may reveal reliable relationships between the genome and schizophrenia, suggesting novel methodological possibilities as well as raising theoretical questions

Polarons and bipolarons in strongly interacting electron-phonon systems

The Holstein Hubbard and Holstein t--J models are studied for a wide range of phonon frequencies, electron--electron and electron--phonon interaction strengths on finite lattices with up to ten sites by means of direct Lanczos diagonalization. Previously the necessary truncation of the phononic Hilbert space caused serious limitations to either very small systems (four or even two sites) or to weak electron--phonon coupling, in particular in the adiabatic regime. Using parallel computers we were able to investigate the transition from `large' to `small' polarons in detail. By resolving the low--lying eigenstates of the Hamiltonian and by calculating the spectral function we can identify a polaron band in the strong--coupling case, whose dispersion deviates from the free--particle dispersion at low and intermediate phonon frequencies. For two electrons (holes) we establish the existence of bipolaronic states and discuss the formation of a bipolaron band. For the 2D Holstein t--J model we demonstrate that the formation of hole--polarons is favoured by strong Coulomb correlations. Analyzing the hole--hole correlation functions we find that hole binding is enhanced as a dynamical effect of the electron--phonon interaction.Comment: 23 pages (Revtex) with 13 figures (ps, uuencoded

Whole genome linkage scan of recurrent depressive disorder from the depression network study

Genome-wide linkage analysis was carried out in a sample of 497 sib pairs concordant for recurrent major depressive disorder (MDD). There was suggestive evidence for linkage on chromosome 1p36 where the LOD score for female-female pairs exceeded 3 (but reduced to 2.73 when corrected for multiple testing). The region includes a gene, MTHFR, that in previous studies has been associated with depressive symptoms. Two other regions, on chromosomes 12q23.3-q24.11 and 13q31.1-q31.3, showed evidence for linkage with a nominal P<0.01. The 12q peak overlaps with a region previously implicated by linkage studies of unipolar and bipolar disorders and contains a gene, DAO, that has been associated with both bipolar disorder and schizophrenia. The 13q peak lies within a region previously linked strongly to panic disorder. A fourth modest peak with an LOD of greater than 1 on chromosome 15q lies within a region that showed genome-wide significant evidence of a recurrent depression locus in a previous sib-pair study. Both the 12q and the 15q findings remained significant at genome-wide level when the data from the present study and the previous reports were combine

Genetic risk prediction and neurobiological understanding of alcoholism

We have used a translational Convergent Functional Genomics (CFG) approach to discover genes involved in alcoholism, by gene-level integration of genome-wide association study (GWAS) data from a German alcohol dependence cohort with other genetic and gene expression data, from human and animal model studies, similar to our previous work in bipolar disorder and schizophrenia. A panel of all the nominally significant P-value single-nucleotide length polymorphisms (SNPs) in the top candidate genes discovered by CFG (n = 135 genes, 713 SNPs) was used to generate a genetic risk prediction score (GRPS), which showed a trend towards significance (P = 0.053) in separating alcohol dependent individuals from controls in an independent German test cohort. We then validated and prioritized our top findings from this discovery work, and subsequently tested them in three independent cohorts, from two continents. In order to validate and prioritize the key genes that drive behavior without some of the pleiotropic environmental confounds present in humans, we used a stress-reactive animal model of alcoholism developed by our group, the D-box binding protein (DBP) knockout mouse, consistent with the surfeit of stress theory of addiction proposed by Koob and colleagues. A much smaller panel (n = 11 genes, 66 SNPs) of the top CFG-discovered genes for alcoholism, cross-validated and prioritized by this stress-reactive animal model showed better predictive ability in the independent German test cohort (P = 0.041). The top CFG scoring gene for alcoholism from the initial discovery step, synuclein alpha (SNCA) remained the top gene after the stress-reactive animal model cross-validation. We also tested this small panel of genes in two other independent test cohorts from the United States, one with alcohol dependence (P = 0.00012) and one with alcohol abuse (a less severe form of alcoholism; P = 0.0094). SNCA by itself was able to separate alcoholics from controls in the alcohol-dependent cohort (P = 0.000013) and the alcohol abuse cohort (P = 0.023). So did eight other genes from the panel of 11 genes taken individually, albeit to a lesser extent and/or less broadly across cohorts. SNCA, GRM3 and MBP survived strict Bonferroni correction for multiple comparisons. Taken together, these results suggest that our stress-reactive DBP animal model helped to validate and prioritize from the CFG-discovered genes some of the key behaviorally relevant genes for alcoholism. These genes fall into a series of biological pathways involved in signal transduction, transmission of nerve impulse (including myelination) and cocaine addiction. Overall, our work provides leads towards a better understanding of illness, diagnostics and therapeutics, including treatment with omega-3 fatty acids. We also examined the overlap between the top candidate genes for alcoholism from this work and the top candidate genes for bipolar disorder, schizophrenia, anxiety from previous CFG analyses conducted by us, as well as cross-tested genetic risk predictions. This revealed the significant genetic overlap with other major psychiatric disorder domains, providing a basis for comorbidity and dual diagnosis, and placing alcohol use in the broader context of modulating the mental landscape