Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies

INTRODUCTION: Restoration of blood flow following ischemic stroke can be achieved by means of thrombolysis or mechanical recanalization. However, for some patients, reperfusion may exacerbate the injury initially caused by ischemia, producing a so-called “cerebral reperfusion injury”. Multiple pathological processes are involved in this injury, including leukocyte infiltration, platelet and complement activation, postischemic hyperperfusion, and breakdown of the blood–brain barrier. METHODS/RESULTS AND CONCLUSIONS: Magnetic resonance imaging (MRI) can provide extensive information on this process of injury, and may have a role in the future in stratifying patients’ risk for reperfusion injury following recanalization. Moreover, different MRI modalities can be used to investigate the various mechanisms of reperfusion injury. Antileukocyte antibodies, brain cooling and conditioned blood reperfusion are potential therapeutic strategies for lessening or eliminating reperfusion injury, and interventionalists may play a role in the future in using some of these therapies in combination with thrombolysis or embolectomy. The present review summarizes the mechanisms of reperfusion injury and focuses on the way each of those mechanisms can be evaluated by different MRI modalities. The potential therapeutic strategies are also discussed

Beam Energy Dependence of Jet-Quenching Effects in Au plus Au Collisions at root s(NN)=7.7, 11.5, 14.5, 19.6, 27, 39, and 62.4 GeV

We report measurements of the nuclear modification factor, $R_{ \mathrm{CP}}$, for charged hadrons as well as identified $\pi^{+(-)}$, $K^{+(-)}$, and $p(\overline{p})$ for Au+Au collision energies of $\sqrt{s_{_{ \mathrm{NN}}}}$ = 7.7, 11.5, 14.5, 19.6, 27, 39, and 62.4 GeV. We observe a clear high-$p_{\mathrm{T}}$ net suppression in central collisions at 62.4 GeV for charged hadrons which evolves smoothly to a large net enhancement at lower energies. This trend is driven by the evolution of the pion spectra, but is also very similar for the kaon spectra. While the magnitude of the proton $R_{ \mathrm{CP}}$ at high $p_{\mathrm{T}}$ does depend on collision energy, neither the proton nor the anti-proton $R_{ \mathrm{CP}}$ at high $p_{\mathrm{T}}$ exhibit net suppression at any energy. A study of how the binary collision scaled high-$p_{\mathrm{T}}$ yield evolves with centrality reveals a non-monotonic shape that is consistent with the idea that jet-quenching is increasing faster than the combined phenomena that lead to enhancement.We report measurements of the nuclear modification factor RCP for charged hadrons as well as identified π+(-), K+(-), and p(p¯) for Au+Au collision energies of sNN=7.7, 11.5, 14.5, 19.6, 27, 39, and 62.4 GeV. We observe a clear high-pT net suppression in central collisions at 62.4 GeV for charged hadrons which evolves smoothly to a large net enhancement at lower energies. This trend is driven by the evolution of the pion spectra but is also very similar for the kaon spectra. While the magnitude of the proton RCP at high pT does depend on the collision energy, neither the proton nor the antiproton RCP at high pT exhibit net suppression at any energy. A study of how the binary collision-scaled high-pT yield evolves with centrality reveals a nonmonotonic shape that is consistent with the idea that jet quenching is increasing faster than the combined phenomena that lead to enhancement

Susceptibility to rheumatoid arthritis is not associated with a single common allele of the type 2 collagen gene (COL2A1)

Type 2 collagen is quantitatively the most important constituent of articular cartilage which is the target of progressive destruction in RA. Polymorphism of type 2 collagen could theoretically influence the development of RA either by rendering the cartilage matrix particularly susceptible to autoimmune attack or subsequent degradation. We have investigated the possibility that there is a common allele of type 2 collagen associated with RA by analysing a dimorphism of the corresponding structural gene (COL2A1) in healthy and diseased individuals. We compared haplotype frequencies, defined by the presence or absence of a Hind III restriction site at the COL2A1 locus (encoding type 2 collagen), in 98 patients with classical/definite RA and 158 controls. No differences were seen between the frequencies of individual genotypes in the two groups (maximum chi 2 = 0.7), indicating that susceptibility to this disease does not appear to be determined by the presence of a single common allelic variant at this locus

Does the locus on chromosome 11 implicated in susceptibility to HLA-DR4 dependent type I diabetes mellitus also affect susceptibility to rheumatoid arthritis?

There is a polygenic component to rheumatoid arthritis (RA) in addition to the known association with HLA-DR4. It has previously been shown in another autoimmune disease (type I diabetes mellitus) that a gene on chromosome 11p can act with HLA-DR4 to enhance susceptibility (relative risk 5-6). It is therefore possible that this locus may also affect the development of RA. Genotype frequencies at this locus, defined by a dimorphic Fok 1 restriction site, were compared in 139 healthy controls and 213 patients with classical/definite RA. In contrast with diabetes there was no increase in genotypes lacking the Fok 1 site, either in the rheumatoid group overall (125/211 compared with 86/139 controls) or in the DR4 positive rheumatoid group (76/140 compared with controls). These results indicate that the interaction between DR4 and a locus on chromosome 11p is not common to all DR4 associated autoimmune diseases

Synovectomy of the elbow and radial head excision in rheumatoid arthritis. Predictive factors and long-term outcome.

We carried out a survival analysis of elbow synovectomy (ES) and excision of the radial head (RHE) performed on 171 rheumatoid elbows. The failure criteria were revision surgery (performed or desired) and/or the presence of significant or severe pain. The cumulative survival was 81% at one year which thereafter decreased by an average of 2.6% per year. The strongest predictor for success was a low preoperative range of supination-pronation when corresponding survival curves were compared. A low range of flexion-extension also predicted failure. Combining both factors gave better prediction (failure: 6.3% v 67%), but a long duration of elbow symptoms before surgery predicted failure (72%, p = 0.04). At review, there was a mean gain of 50 degrees in supination-pronation and 11 degrees in flexion-extension; both correlated with success. Failure correlated with recurrence of synovitis, elbow instability, ulnar neuropathy, poor general mobility and poor upper-limb function. The last was independently affected by the severity of RA in the ipsilateral shoulder. Our findings show that although the short-term result of ES and RHE in rheumatoid arthritis is good, the long-term outcome is poor except in a subgroup with more than 50% limitation of forearm rotation