30 research outputs found
Systemic adalimumab induces peripheral corneal infiltrates: a case report.
BACKGROUND: Tumor necrosis factor-alpha inhibitors are widely used agents in the treatment of immune disorders such as rheumatoid arthritis and inflammatory bowel disease. Despite their anti-inflammatory action, paradoxical drug-induced inflammatory events have been occasionally associated with the use of infliximab, etanercept, and in a lesser extent adalimumab. However, eye involvement is uncommon and anterior uveitis is the only reported ocular adverse manifestation. It can be induced by etanercept, but has also been described during adalimumab therapy. We present here the first report of recurrent peripheral corneal infiltrates following subcutaneous injections of adalimumab.
CASE PRESENTATION: A 34 year-old Caucasian woman with Crohn's disease presented to the emergency department with bilateral red eyes and discomfort 36 hours after she received her bimonthly dose of subcutaneous adalimumab. Examination revealed bilateral peripheral corneal infiltrates with characteristic features of immune infiltrates. Symptoms and infiltrates regressed after topical corticosteroid therapy, but recurred after each adalimumab injection over the following weeks.
CONCLUSION: Paradoxical immune reactions associated with tumor necrosis factor-alpha inhibitors may result either from hypersensitivity mechanisms, or from immune-complex deposition via anti-adalimumab antibodies. Both mechanisms could explain this newly described manifestation. Care should be taken to search for corneal infiltrates in the event of red eye symptoms during adalimumab therapy since they respond to topical corticosteroids and do not necessarily prompt the discontinuation of the immunosuppressive therapy
Multimodal Highlighting of Structural Abnormalities in Diabetic Rat and Human Corneas.
PURPOSE: This study aimed to highlight structural corneal changes in a model of type 2 diabetes, using in vivo corneal confocal microscopy (CCM). The abnormalities were also characterized by transmission electron microscopy (TEM) and second harmonic generation (SHG) microscopy in rat and human corneas.
METHODS: Goto-Kakizaki (GK) rats were observed at age 12 weeks (n = 3) and 1 year (n = 6), and compared to age-matched controls. After in vivo CCM examination, TEM and SHG microscopy were used to characterize the ultrastructure and the three-dimensional organization of the abnormalities. Human corneas from diabetic (n = 3) and nondiabetic (n = 3) patients were also included in the study.
RESULTS: In the basal epithelium of GK rats, CCM revealed focal hyper-reflective areas, and histology showed proliferative cells with irregular basement membrane. In the anterior stroma, extracellular matrix modifications were detected by CCM and confirmed in histology. In the Descemet's membrane periphery of all the diabetic corneas, hyper-reflective deposits were highlighted using CCM and characterized as long-spacing collagen fibrils by TEM. SHG microscopy revealed these deposits with high contrast, allowing specific detection in diabetic human and rat corneas without preparation and characterization of their three-dimensional organization.
CONCLUSION: Pathologic findings were observed early in the development of diabetes in GK rats. Similar abnormalities have been found in corneas from diabetic patients.
TRANSLATIONAL RELEVANCE: This multidisciplinary study highlights diabetes-induced corneal abnormalities in an animal model, but also in diabetic donors. This could constitute a potential early marker for diagnosis of hyperglycemia-induced tissue changes
Hidden Order in the Cuprates
We propose that the enigmatic pseudogap phase of cuprate superconductors is
characterized by a hidden broken symmetry of d(x^2-y^2)-type. The transition to
this state is rounded by disorder, but in the limit that the disorder is made
sufficiently small, the pseudogap crossover should reveal itself to be such a
transition. The ordered state breaks time-reversal, translational, and
rotational symmetries, but it is invariant under the combination of any two. We
discuss these ideas in the context of ten specific experimental properties of
the cuprates, and make several predictions, including the existence of an
as-yet undetected metal-metal transition under the superconducting dome.Comment: 12 pages of RevTeX, 9 eps figure
Resonance peak in underdoped cuprates
The magnetic susceptibility measured in neutron scattering experiments in
underdoped YBaCuO is interpreted based on the self-consistent
solution of the t-J model of a Cu-O plane. The calculations reproduce correctly
the frequency and momentum dependencies of the susceptibility and its variation
with doping and temperature in the normal and superconducting states. This
allows us to interpret the maximum in the frequency dependence -- the resonance
peak -- as a manifestation of the excitation branch of localized Cu spins and
to relate the frequency of the maximum to the size of the spin gap. The
low-frequency shoulder well resolved in the susceptibility of superconducting
crystals is connected with a pronounced maximum in the damping of the spin
excitations. This maximum is caused by intense quasiparticle peaks in the hole
spectral function for momenta near the Fermi surface and by the nesting.Comment: 9 pages, 6 figure
Dispersion of Ordered Stripe Phases in the Cuprates
A phase separation model is presented for the stripe phase of the cuprates,
which allows the doping dependence of the photoemission spectra to be
calculated. The idealized limit of a well-ordered array of magnetic and charged
stripes is analyzed, including effects of long-range Coulomb repulsion.
Remarkably, down to the limit of two-cell wide stripes, the dispersion can be
interpreted as essentially a superposition of the two end-phase dispersions,
with superposed minigaps associated with the lattice periodicity. The largest
minigap falls near the Fermi level; it can be enhanced by proximity to a (bulk)
Van Hove singularity. The calculated spectra are dominated by two features --
this charge stripe minigap plus the magnetic stripe Hubbard gap. There is a
strong correlation between these two features and the experimental
photoemission results of a two-peak dispersion in LaSrCuO, and
the peak-dip-hump spectra in BiSrCaCuO. The
differences are suggestive of the role of increasing stripe fluctuations. The
1/8 anomaly is associated with a quantum critical point, here expressed as a
percolation-like crossover. A model is proposed for the limiting minority
magnetic phase as an isolated two-leg ladder.Comment: 24 pages, 26 PS figure
Genotype-phenotype correlations of TGFBI p.Leu509Pro, p.Leu509Arg, p.Val613Gly, and the allelic association of p.Met502Val-p.Arg555Gln mutations.
Investigate the genotype-phenotype correlations for five TGFBI (transforming growth factor, beta-induced) mutations including one novel pathogenic variant and one complex allele affecting the fourth FAS1 domain of keratoepithelin, and their potential effects on the protein's structure.
Three unrelated families were clinically diagnosed with lattice corneal dystrophy (CD) and one with an unclassified CD of Bowman's layer. Mutations in the TGFBI gene were detected by direct sequencing, and the functional impact of each variant was predicted using in silico algorithms. Corneal phenotypes, including histological examinations, were compared with the literature data. Furthermore, molecular modeling studies of these mutations were performed.
Two distinct missense mutations affecting the same residue at position 509 of keratoepithelin: p.Leu509Pro (c.1526T>C) and p.Leu509Arg (c.1526T>G) were found to be associated with a lattice-type CD. The novel p.Val613Gly (c.1828T>G) TGFBI mutation was found in a sporadic case of an Algerian individual affected by lattice CD. Finally, the Bowman's layer CD was linked to the association in cis of the p.Met502Val and p.Arg555Gln variants, leading to the reclassification of this CD as atypical Thiel-Behnke CD. Structural modeling of these TGFBI mutations argues in favor of these mutations being responsible for instability and/or incorrect folding of keratoepithelin, predictions that are compatible with the clinical diagnoses.
Description of a novel TGFBI mutation and a complex TGFBI allele further extends the mutational spectrum of TGFBI. Moreover, we show convincing evidence that TGFBI mutations affecting Leu509 are linked to the lattice phenotype in two unrelated French families, contrasting with findings previously reported. The p.Leu509Pro was reported to be associated with both amyloid and non-amyloid aggregates, whereas p.Leu509Arg has been described as being responsible for Epithelial Basement Membrane Dystrophy (EBMD)
Magnetic Properties of YBa_2Cu_3O_{7-\delta} in a self-consistent approach: Comparison with Quantum-Monte-Carlo Simulations and Experiments
We analyze single-particle electronic and two-particle magnetic properties of
the Hubbard model in the underdoped and optimally-doped regime of \YBCO by
means of a modified version of the fluctuation-exchange approximation, which
only includes particle-hole fluctuations. Comparison of our results with
Quantum-Monte Carlo (QMC) calculations at relatively high temperatures () suggests to introduce a temperature renormalization in order to
improve the agreement between the two methods at intermediate and large values
of the interaction .
We evaluate the temperature dependence of the spin-lattice relaxation time
and of the spin-echo decay time and compare it with the results
of NMR measurements on an underdoped and an optimally doped \YBCO sample. For
it is possible to consistently adjust the parameters of the Hubbard
model in order to have a good {\it semi-quantitative} description of this
temperature dependence for temperatures larger than the spin gap as obtained
from NMR measurements. We also discuss the case , which is more
appropriate to describe magnetic and single-particle properties close to
half-filling. However, for this larger value of the agreement with QMC as
well as with experiments at finite doping is less satisfactory.Comment: Final version, to appear in Phys. Rev. B (sched. Feb. 99
Competing orders in a magnetic field: spin and charge order in the cuprate superconductors
We describe two-dimensional quantum spin fluctuations in a superconducting
Abrikosov flux lattice induced by a magnetic field applied to a doped Mott
insulator. Complete numerical solutions of a self-consistent large N theory
provide detailed information on the phase diagram and on the spatial structure
of the dynamic spin spectrum. Our results apply to phases with and without
long-range spin density wave order and to the magnetic quantum critical point
separating these phases. We discuss the relationship of our results to a number
of recent neutron scattering measurements on the cuprate superconductors in the
presence of an applied field. We compute the pinning of static charge order by
the vortex cores in the `spin gap' phase where the spin order remains
dynamically fluctuating, and argue that these results apply to recent scanning
tunnelling microscopy (STM) measurements. We show that with a single typical
set of values for the coupling constants, our model describes the field
dependence of the elastic neutron scattering intensities, the absence of
satellite Bragg peaks associated with the vortex lattice in existing neutron
scattering observations, and the spatial extent of charge order in STM
observations. We mention implications of our theory for NMR experiments. We
also present a theoretical discussion of more exotic states that can be built
out of the spin and charge order parameters, including spin nematics and phases
with `exciton fractionalization'.Comment: 36 pages, 33 figures; for a popular introduction, see
http://onsager.physics.yale.edu/superflow.html; (v2) Added reference to new
work of Chen and Ting; (v3) reorganized presentation for improved clarity,
and added new appendix on microscopic origin; (v4) final published version
with minor change
Carrier relaxation, pseudogap, and superconducting gap in high-Tc cuprates: A Raman scattering study
We describe results of electronic Raman-scattering experiments in differently
doped single crystals of Y-123 and Bi-2212. The comparison of AF insulating and
metallic samples suggests that at least the low-energy part of the spectra
originates predominantly from excitations of free carriers. We therefore
propose an analysis of the data in terms of a memory function approach.
Dynamical scattering rates and mass-enhancement factors for the carriers are
obtained. In B2g symmetry the Raman data compare well to the results obtained
from ordinary and optical transport. For underdoped materials the dc scattering
rates in B1g symmetry become temperature independent and considerably larger
than in B2g symmetry. This increasing anisotropy is accompanied by a loss of
spectral weight in B2g symmetry in the range between the superconducting
transition at Tc and a characteristic temperature T* of order room temperature
which compares well with the pseudogap temperature found in other experiments.
The energy range affected by the pseudogap is doping and temperature
independent. The integrated spectral loss is approximately 25% in underdoped
samples and becomes much weaker towards higher carrier concentration. In
underdoped samples, superconductivity related features in the spectra can be
observed only in B2g symmetry. The peak frequencies scale with Tc. We do not
find a direct relation between the pseudogap and the superconducting gap.Comment: RevTeX, 21 pages, 24 gif figures. For PostScript with embedded eps
figures, see http://www.wmi.badw-muenchen.de/~opel/k2.htm
Spin-Charge Separation in the Model: Magnetic and Transport Anomalies
A real spin-charge separation scheme is found based on a saddle-point state
of the model. In the one-dimensional (1D) case, such a saddle-point
reproduces the correct asymptotic correlations at the strong-coupling
fixed-point of the model. In the two-dimensional (2D) case, the transverse
gauge field confining spinon and holon is shown to be gapped at {\em finite
doping} so that a spin-charge deconfinement is obtained for its first time in
2D. The gap in the gauge fluctuation disappears at half-filling limit, where a
long-range antiferromagnetic order is recovered at zero temperature and spinons
become confined. The most interesting features of spin dynamics and transport
are exhibited at finite doping where exotic {\em residual} couplings between
spin and charge degrees of freedom lead to systematic anomalies with regard to
a Fermi-liquid system. In spin dynamics, a commensurate antiferromagnetic
fluctuation with a small, doping-dependent energy scale is found, which is
characterized in momentum space by a Gaussian peak at (, ) with
a doping-dependent width (, is the doping
concentration). This commensurate magnetic fluctuation contributes a
non-Korringa behavior for the NMR spin-lattice relaxation rate. There also
exits a characteristic temperature scale below which a pseudogap behavior
appears in the spin dynamics. Furthermore, an incommensurate magnetic
fluctuation is also obtained at a {\em finite} energy regime. In transport, a
strong short-range phase interference leads to an effective holon Lagrangian
which can give rise to a series of interesting phenomena including linear-
resistivity and Hall-angle. We discuss the striking similarities of these
theoretical features with those found in the high- cuprates and give aComment: 70 pages, RevTex, hard copies of 7 figures available upon request;
minor revisions in the text and references have been made; To be published in
July 1 issue of Phys. Rev. B52, (1995