Return to dialysis after renal transplantation. Which would be the best way?

The exact moment to return to dialysis when a graft fails has not clearly been established. Furthermore, there is no agreement with respect to whether the guidelines accepted for patients entering dialysis for the first time are adequate for this subgroup of patients with advanced renal failure, due to the special characteristics of these patients, derived from the immunosuppressive medications they are taking among other accompanying factors. We reviewed a group of renal transplant patients who returned to dialysis and compared them with a group of patients entering dialysis for the first time. Patients with chronic renal failure due to graft failure had a poorer renal function at the time entering dialysis and a more profound anemia. Additionally, complications considered such as the number of hospital admissions during the first year after initiation of dialysis were considerably higher in the group of transplanted patients. We advocate for an earlier referral to the dialysis unit, a more aggressive erythropoietin therapy in the phase of advanced renal failure due to chronic allograft nephropathy, and in selected cases retransplantation before definitive graft loss.     

Mechanism of vascular smooth muscle cells activation by hydrogen peroxide: role of phospholipase C gamma.

BACKGROUND: Hydrogen peroxide (H2O2) formation is a critical factor in processes involving ischaemia/ reperfusion. However, the precise mechanism by which reactive oxygen species (ROS) induce vascular damage are insufficiently known. Specifically, activation of phospholipase C gamma (PLCgamma) is a probable candidate pathway involved in vascular smooth muscle cells (VSMC) activation by H2O2. METHODS: The activation of human venous VSMC was measured as cytosolic free calcium mobilization, shape change and protein phosphorylation, focusing on the role of tyrosine phosphorylation-activated PLCgamma. RESULTS: The exposure of VSMC to exogenous H2O2 caused a rapid increase in cytosolic free calcium concentration ([Ca2+]i), and induced a significant VSMC shape change. Both effects were dependent on a tyrosine kinase-mediated mechanism, as determined by the blockade of short-term treatment of VSMC with the protein tyrosine kinase inhibitor, genistein. Giving further support to the putative role of phospholipase C (PLC)-dependent pathways, the [Ca2+]i and VSMC shape change response were equally inhibited by the specific PLC blocker, 1-(6-((17-beta-methoxyestra-1,3,5(10)trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). In addition, U73122 had a protective effect against the deleterious action (24 h) of H2O2 on non-confluent VSMC. As a further clarification of the specific pathway involved, the exposure to H2O2 significantly stimulated the tyrosine phosphorylation of PLCgamma with a concentration- and time-profile similar to that of [Ca(2+)](i) mobilization. CONCLUSIONS: The present study reveals that H(2)O(2) activates PLCgamma on VSMC through tyrosine phosphorylation and that this activation has a major role in rapid [Ca(2+)](i) mobilization, shape-changing actions and damage by H(2)O(2) in this type of cells. These findings have direct implications for understanding the mechanisms of the vascular actions of H(2)O(2) and may help to design pharmacologically protective strategies.     

Scrotal cystic hygroma in a 13-year-old boy

We describe a patient with cystic hygroma, in a rare location (scrotum). The hygroma was diagnosed incidentally after injury to the scrotum in a 13-year-old boy. The diagnostic methods used, the characteristics of this type of tumor, its treatment and its clinical course are described. We suggest that cystic hygroma be taken into account in the differential diagnosis of other more frequent causes of scrotal masses.     

The Prevalence of Groin Pain After Metal-on-Metal Total Hip Arthroplasty and Total Hip Resurfacing

Background  

Groin pain after total hip arthroplasty (THA) or total hip resurfacing arthroplasty can be troubling for patients and surgeons. Potential sources of pain include infection, loosening, metal hypersensitivity, or impingement of bony structures or the iliopsoas tendon.     

Evaluation of the Rebound Hernia Repair Device for Laparoscopic Hernia Repair

Background:

The characteristics of the ideal type of mesh are still being debated. Mesh shrinkage and fixation have been associated with complications. Avoiding shrinkage and fixation would improve hernia recurrence rates and complications. To our knowledge, this is the first study of a device with a self-expanding frame for laparoscopic hernia repair.

Methods:

Six Rebound Hernia Repair Devices were placed laparoscopically in pigs. This device is a condensed polypropylene, super-thin, lightweight, macro-porous mesh with a self-expanding Nitinol frame. The devices were assessed for adhesions, shrinkage, and histological examination. Laboratory and radiologic evaluations were also performed.

Results:

The handling properties of the devices facilitated their laparoscopic placement. They were easily identified with simple x-rays. The mesh was firmly integrated within the surrounding tissue. One device was associated with 3 small adhesions. The other 5 HRDs had no adhesions. We noted no shrinkage or folding. All devices preserved their original size and shape.

Conclusions:

At this evaluation stage, we found that the Rebound Hernia Repair Device may serve for laparoscopic hernia repair and has favorable handling properties. It prevents folding and shrinkage of the mesh. It may eliminate the need for fixation, thus preventing chronic pain. The Nitinol frame also allowed radiologic evaluation for gross movement. Further studies will be needed to evaluate its clinical application.     

Sub-exemplar shape tuning in human face-related areas

Although human face recognition performance shows high selectivity, even for unfamiliar faces, the neuronal circuitry underlying this high performance is poorly understood. Two extreme alternatives can be considered: either a "labeled-line" principle, in which subtle changes in face images lead to activation of differently tuned neuronal populations, or a coarse coding principle, where the high face selectivity is coded by the relative activation of broadly tuned neurons. In this study, we set to parametrically examine the shape and selectivity profile of face-related visual areas. To that end, we applied the functional magnetic resonance (fMR)-adaptation paradigm. Unfamiliar face stimuli were morphed into sets ranging from identical faces, through subtle morphing, to completely different exemplars. The fusiform face area (FFA) revealed high face sensitivity, so that even facial images perceived as belonging to the same individual (<35%) were sufficient to produce full recovery from adaptation. Interestingly, the psychophysical detectability of facial differences paralleled the release from fMR-adaptation. These results support the labeled-line model where high sensitivity to face changes is paralleled by narrow tuning of neuronal populations selective to each face image, and they suggest that fMR-adaptation is closely related to behavior. The results bear strong implications to the nature of face-related neuronal responses.     

Use of a Roux Limb to Correct Esophagogastric Junction Fistulas after Sleeve Gastrectomy

Laparoscopic sleeve gastrectomy (LSG) can be complicated, in the early postoperative course, by an esophagogastric junction (EGJ) leak with very serious consequences. A 48-year-old woman developed an EGJ leak 3 days after LSG surgery and was treated with conservative measures. Finally, 6 weeks after the original surgery, a Roux limb was brought to the EGJ and anastomosed side-to-end to the fistula. At the beginning, the Roux limb was the only functioning outlet and finally, 2 months later, both pathways (the gastric sleeve and the Roux-en-Y) are patent at 3 months after surgery. The Roux limb resolved a dangerous EGJ leak after a LSG.     

Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress

The high-metabolic demand of neurons and their reliance on glucose as an energy source places them atrisk for dysfunction and death under conditions of metabolic and oxidative stress. Uncoupling proteins (UCPs) are mitochodrial inner membrane proteins implicated in the regulation of mitochondrial membrane potential (ΔΨ_m) and cellular energy metabolism. The authors cloned UCP4 cDNA from mouse and rat brain, and demonstrate that UCP4 mRNA is expressed abundantly in brain and at particularly high levels in populations of neurons believed to have high-energy requirements. Neural cells with increased levels of UCP4 exhibit decreased ΔΨ_m, reduced reactive oxygen species (ROS) production and decreased mitochondrial calcium accumulation. UCP4 expressing cells also exhibited changes of oxygen-consumption rate, GDP sensitivity, and response of ΔΨ_m to oligomycin that were consistent with mitochondrial uncoupling. UCP4 modulates neuronal energy metabolism by increasing glucose uptake and shifting the mode of ATP production from mitochodnrial respiration to glycolysis, thereby maintaining cellular ATP levels. The UCP4-mediated shift in energy metabolism reduces ROS production and increases the resistance of neurons to oxidative and mitochondrial stress. Knockdown of UCP4 expression by RNA interference in primary hippocampal neurons results in mitochondrial calcium overload and cell death. UCP4-mRNA expression is increased in neurons exposed to cold temperatures and in brain cells of rats maintained on caloric restriction, suggesting a role for UCP4 in the previously reported antiageing and neuroprotective effects of caloric restriction. By shifting energy metabolism to reduce ROS production and cellular reliance on mitochondrial respiration, UCP4 can protect neurons against oxidative stress and calcium overload. These authors made equal contributions to this research.     

Pro-epileptic effect of alfentanil in rats subjected to pilocarpine-induced chronic epilepsy

Pharmacological induction of epileptiform activity is a complementary method to study the epileptogenic area in drug-resistant epileptic patients. Among the different activation methods, fentanyl derivatives (e.g. alfentanil) provide one of the most efficient tools in triggering epileptiform abnormalities in surgical candidates. In this study, we tested the pro-epileptic effect of different concentrations of alfentanil in hippocampal slices obtained from control and pilocarpine-treated chronic epileptic rats. The pro-convulsant action of alfentanil was also studied in control and pilocarpine-treated epileptic rats implanted with subdural and hippocampal electrodes for electroencephalographic recordings. In 90% of slices from control animals, application of alfentanil (0.1-5 microM) induced a significant enhancement in amplitude and number of population spikes recorded in the hippocampal CA1 region. In contrast, alfentanil produced a significant reduction in the amplitude of population spikes in slices from pilocarpine-treated epileptic rats. These changes were accompanied by a significant increase in the number of population spikes in the form of epileptiform multispike responses of epileptic slices. Naloxone (20 microM) antagonized the effect of alfentanil in both control and epileptic slices, reducing the number of population spikes in slices from epileptic rats. In control rats, alfentanil induced epileptiform abnormalities in the hippocampal and cortical electroencephalographic recordings but only at concentrations higher than 200 microg/kg (e.g. 350 microg/kg). Lower doses of alfentanil (25 microg/kg) elicited epileptiform abnormalities only in chronic epileptic rats. The potent action of a minimal dose of alfentanil in inducing epileptiform activity suggests an enhancement of the pro-convulsant action of mu-receptor opioids in chronic temporal lobe epilepsy.     

Neutralization of the chemokine CXCL10 reduces apoptosis and increases axon sprouting after spinal cord injury

Spinal cord injury (SCI) is followed by a secondary degenerative process that includes cell death. We have previously demonstrated that the chemokine CXCL10 is up-regulated following SCI and plays a critical role in T-lymphocyte recruitment to sites of injury and inhibition of angiogenesis; antibody-mediated functional blockade of CXCL10 reduced inflammation while enhancing angiogenesis. We hypothesized, based on these findings, that the injury environment established by anti-CXCL10 antibody treatment would support greater survival of neurons and enhance axon sprouting compared with the untreated, injured spinal cord. Here, we document gene array and histopathological data to support our hypothesis. Gene array analysis of treated and untreated tissue from spinal cord-injured animals revealed eight apoptosis-related genes with significant expression changes at 3 days postinjury. In support of these data, quantification of TUNEL-positive cells at 3 days postinjury indicated a 75% reduction in the number of dying cells in treated animals compared with untreated animals. Gene array analysis of treated and untreated tissue also revealed six central nervous system growth-related genes with significant expression changes in the brainstem at 14 days postinjury. In support of these data, quantification of anterograde-labeled corticospinal tract fibers indicated a 60-70% increase in axon sprouting caudal to the injury site in treated animals compared with untreated animals. These findings indicate that anti-CXCL10 antibody treatment provides an environment that reduces apoptosis and increases axon sprouting following injury to the adult spinal cord.