Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

1. Download : Download high-res image (301KB)
2. Download : Download full-size image

     

Continuous Preperitoneal Infusion of Ropivacaine Provides Effective Analgesia and Accelerates Recovery after Colorectal Surgery: A Randomized, Double-blind, Placebo-controlled Study

Background: Blockade of parietal nociceptive afferents by the use of continuous wound infiltration with local anesthetics may be beneficial in a multimodal approach to postoperative pain management after major surgery. The role of continuous preperitoneal infusion of ropivacaine for pain relief and postoperative recovery after open colorectal resections was evaluated in a randomized, double-blinded, placebo-controlled trial.

Methods: After obtaining written informed consents, a multiholed wound catheter was placed by the surgeon in the preperitoneal space at the end of surgery in patients scheduled to undergo elective open colorectal resection by midline incision. They were thereafter randomly assigned to receive through the catheter either 0.2% ropivacaine (10-ml bolus followed by an infusion of 10 ml/h during 48 h) or the same protocol with 0.9% NaCl. In addition, all patients received patient-controlled intravenous morphine analgesia.

Results: Twenty-one patients were evaluated in each group. Compared with preperitoneal saline, ropivacaine infusion reduced morphine consumption during the first 72 h and improved pain relief at rest during 12 h and while coughing during 48 h. Sleep quality was also better during the first two postoperative nights. Time to recovery of bowel function (74 +/- 19 vs. 105 +/- 54 h; P = 0.02) and duration of hospital stay (115 +/- 25 vs. 147 +/- 53 h; P = 0.02) were significantly reduced in the ropivacaine group. Ropivacaine plasma concentrations remained below the level of toxicity. No side effects were observed.     

Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol

Previous studies of propofol (2,6-diisopropylphenol) pharmacology have shown that this widely used anaesthetic drug is extensively cleared from the body by conjugation of the parent molecule or its quinol metabolite. On the basis of potential influence of propofol on the metabolism of co-administered agents, many investigators have evaluated the effects of propofol on cytochrome P450 (CYP) activities. CYP isoforms involved in propofol metabolism are not defined. In this study, our objective was to elucidate further the CYP isoforms responsible for the hydroxylation of propofol. Using microsomes from 12 different human livers, we investigated CYP isoforms involved in propofol hydroxylase activity, using selective chemical inhibitors of CYP isoforms, correlation with immunoquantified specific CYP isoform content, immunoinhibition, and 11 functionally active human CYP isoforms expressed in a heterologous system (yeast and human B- lymphoblastoid cells). We found a low variability in the production of the hydroxylated metabolite of propofol, 2,6-diisopropyl-1,4-quinol. This activity was mediated by CYP and followed Michaelis-Menten kinetics with apparent K(M) and Vmax values of 18 microM (95% Cl 15.1- 20.1) and 2.6 nmol min-1 mg-1 (95% Cl 2.45-2.68) respectively. Part of the propofol hydroxylase activity was mediated by CYP2C9 in human liver, especially at low substrate concentration. Moreover, propofol was likely to be metabolized by additional isoforms such as CYP2A6, 2C8, 2C18, 2C19 and 1A2, especially when substrate concentrations are high. This low specificity among CYP isoforms may contribute to the low interindividual variability (two-fold) and may contribute to the low level of metabolic drug interactions observed with propofol.      

In multiple-step gaze shifts: omnipause (OPNs) and collicular fixation neurons encode gaze position error; OPNs gate saccades

The superior colliculus (SC), via its projections to the pons, is a critical structure for driving rapid orienting movements of the visual axis, called gaze saccades, composed of coordinated eye-head movements. The SC contains a motor map that encodes small saccade vectors rostrally and large ones caudally. A zone in the rostral pole may have a different function. It contains superior colliculus fixation neurons (SCFNs) with probable projections to omnipause neurons (OPNs) of the pons. SCFNs and OPNs discharge tonically during visual fixation and pause during single-step gaze saccades. The OPN tonic discharge inhibits saccades and its cessation (pause) permits saccade generation. We have proposed that SCFNs control the OPN discharge. We compared the discharges of SCFNs and OPNs recorded while cats oriented horizontally, to the left and right, in the dark to a remembered target. Cats used multiple-step gaze shifts composed of a series of small gaze saccades, of variable amplitude and number, separated by periods of variable duration (plateaus) in which gaze was immobile or moving at low velocity (<25 degrees /s). Just after contralaterally (ipsilaterally) presented targets, the firing frequency of SCFNs decreased to almost zero (remained constant at background). As multiple-step gaze shifts progressed in either direction in the dark, these activity levels prevailed until the distance between gaze and target [gaze position error (GPE)] reached approximately 16 degrees. At this point, firing frequency gradually increased, without saccade-related pauses, until a maximum was reached when gaze arrived on target location (GPE = 0 degrees). SCFN firing frequency encoded GPE; activity was not correlated to characteristics or occurrence of gaze saccades. By comparison, after target presentation to left or right, OPN activity remained steady at pretarget background until first gaze saccade onset, during which activity paused. During the first plateau, activity resumed at a level lower than background and continued at this level during subsequent plateaus until GPE approximately 8 degrees was reached. As GPE decreased further, tonic activity during plateaus gradually increased until a maximum (greater than background) was reached when gaze was on goal (GPE = 0 degrees). OPNs, like SCFNs, encoded GPE, but they paused during every gaze saccade, thereby revealing, unlike for SCFNs, strong coupling to motor events. The firing frequency increase in SCFNs as GPE decreased, irrespective of trajectory characteristics, implies these cells get feedback on GPE, which they may communicate to OPNs. We hypothesize that at the end of a gaze-step sequence, impulses from SCFNs onto OPNs may suppress further movements away from the target.     

Three-dimensional eye-head coordination during gaze saccades in the primate

The purpose of this investigation was to describe the neural constraints on three-dimensional (3-D) orientations of the eye in space (Es), head in space (Hs), and eye in head (Eh) during visual fixations in the monkey and the control strategies used to implement these constraints during head-free gaze saccades. Dual scleral search coil signals were used to compute 3-D orientation quaternions, two-dimensional (2-D) direction vectors, and 3-D angular velocity vectors for both the eye and head in three monkeys during the following visual tasks: radial to/from center, repetitive horizontal, nonrepetitive oblique, random (wide 2-D range), and random with pin-hole goggles. Although 2-D gaze direction (of Es) was controlled more tightly than the contributing 2-D Hs and Eh components, the torsional standard deviation of Es was greater (mean 3.55 degrees ) than Hs (3.10 degrees ), which in turn was greater than Eh (1.87 degrees ) during random fixations. Thus the 3-D Es range appeared to be the byproduct of Hs and Eh constraints, resulting in a pseudoplanar Es range that was twisted (in orthogonal coordinates) like the zero torsion range of Fick coordinates. The Hs fixation range was similarly Fick-like, whereas the Eh fixation range was quasiplanar. The latter Eh range was maintained through exquisite saccade/slow phase coordination, i.e., during each head movement, multiple anticipatory saccades drove the eye torsionally out of the planar range such that subsequent slow phases drove the eye back toward the fixation range. The Fick-like Hs constraint was maintained by the following strategies: first, during purely vertical/horizontal movements, the head rotated about constantly oriented axes that closely resembled physical Fick gimbals, i.e., about head-fixed horizontal axes and space-fixed vertical axes, respectively (although in 1 animal, the latter constraint was relaxed during repetitive horizontal movements, allowing for trajectory optimization). However, during large oblique movements, head orientation made transient but dramatic departures from the zero-torsion Fick surface, taking the shortest path between two torsionally eccentric fixation points on the surface. Moreover, in the pin-hole goggle task, the head-orientation range flattened significantly, suggesting a task-dependent default strategy similar to Listing's law. These and previous observations suggest two quasi-independent brain stem circuits: an oculomotor 2-D to 3-D transformation that coordinates anticipatory saccades with slow phases to uphold Listing's law, and a flexible "Fick operator" that selects head motor error; both nested within a dynamic gaze feedback loop.     

Impact of Cold Ischemia Time on the Function of Liver Grafts Preserved With Custodiol

ObjectiveThis study aimed to evaluate how cold ischemia time (CIT) interferes with liver graft function in the first 7 days after surgery for Custodiol (HTK) preserved organs.MethodsThis retrospective observational study analyzed the medical records of 38 transplantation patients at Hospital Leforte Liberdade, São Paulo, in 2018. The study population was divided into 2 groups (group A, CIT < 8 hours; group B, CIT > 8 hours). Postoperative parameters—such as international normalized ratio, total bilirubin, aspartate aminotransferase/alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase (GGT), lactate dehydrogenase, lactate, creatinine, red blood cell transfusion, need for hemodialysis, use of vasoactive drugs, endotracheal intubation time, length of stay in the intensive care unit (ICU), and length of hospital stay—were compared.ResultsGroup A (CIT < 8 hours) presented less need for red blood cell transfusions (odds ratio 0.29; confidence interval 0.06-0.98; P = .04), had a shorter hospital stay (P = .024), and had lower levels of total bilirubin (P = .05) and GGT (P = .05) in the first 7 postoperative days. The other variables showed no statistically significant difference.ConclusionIn livers preserved with Custodiol, CIT > 8 hours generated higher levels of total bilirubin and GGT in the postoperative period, in addition to higher hospital costs; greater need for red blood cell transfusions; and longer hospitalization, including longer stays in the ICU.     

Upper eyelid movements measured with a search coil during blinks and vertical saccades.

Upper eyelid movements were recorded in nine human subjects by mounting a miniature coil of wire directly on the eyelid and subjecting the search coil to a vertically directed alternating magnetic field. The metrics of blinks and lid movements accompanying saccades were described by "main sequence" relationships, linking maximum velocity to amplitude and duration to amplitude. In general, lid movements were faster than those reported previously in the literature, but there was considerable intersubject variability. On average, the main sequence relationships for blinks were independent of either starting lid position or whether the blinks were generated spontaneously, reflexively, or voluntarily. For the down phase of the average blink, both the maximum velocity and duration increased almost linearly with amplitude. The maximum velocity of the down phase was faster than that of the up phase. For lid movements accompanying vertical saccades, the maximum velocities in the up and down directions were similar and increased nonlinearly with amplitude, saturating at about 120 mm/sec (approximately 450 degrees/sec). Duration increased approximately linearly with amplitude. The down phases of blinks were much faster than those of saccade-related lid movements. By comparison, the maximum velocities of the up phase of blinks and of saccade-related lid movements were almost equal. The large intersubject variability suggests caution when using normative data to interpret abnormal lid motion for clinical purposes.