Outcomes of Endovascular Management of Late Vascular Hemorrhage After Pancreatic Transplant.

OBJECTIVE: The aim of this retrospective study is to evaluate the endovascular treatment of hemorrhage in the nonperioperative setting in pancreas transplant recipients. MATERIALS AND METHODS: All angiograms performed between January 1, 1999, and June 1, 2016, to treat hemorrhage after pancreatic transplant at a single large-volume transplant center were reviewed. Fourteen patients who underwent 21 angiograms were identified. The patients' charts were reviewed for clinical indications, technical aspects of the endovascular interventions, outcomes, and complications. RESULTS: The mean number of angiograms was 1.5 per patient. The primary and primary assisted clinical success rates were 64.3% (9/14 patients) and 71.4% (10/14 patients), respectively. Five patients (35.7%) experienced complications. At presentation, eight patients had functioning grafts and seven of these eight patients (87.5%) maintained graft function. CONCLUSION: It is critical to recognize transplant-related hemorrhage after pancreas transplant. Endovascular management is associated with high clinical success and rarely results in loss of graft function, suggesting that it should be a consideration for first-line therapy in this patient population.

Naltrexone aversion and treatment efficacy are greatest in humans and rats that actively consume high levels of alcohol.

The opioid antagonist naltrexone is the standard pharmacotherapy for alcoholism, although compliance is often low. The mechanism by which naltrexone reduces drinking is yet unclear. Here we show that in active alcoholics the magnitude of naltrexone treatment efficacy is correlated with the level of naltrexone-induced aversive side effects. This correlation is not observed when subjects are sober, but emerges following alcohol administration, when subjects are intoxicated. In contrast, there is no correlation following placebo administration. To clarify these results, naltrexone was administered to ethanol-consuming rats prior to quantification of naltrexone aversion. Ethanol consumption preceding naltrexone treatment was again correlated with subsequent naltrexone-induced aversion, and this aversion correlated with subsequent decrease in ethanol consumption. In contrast, when naltrexone was given to ethanol-free rats, aversion was not predictive of ethanol consumption. We conclude that naltrexone treatment efficacy is greater during active ethanol consumption and may be partly due to aversive side effects.

The influence of feedback valence in associative learning.

The neural systems engaged by intrinsic positive or negative feedback were defined in an associative learning task. Through trial and error, participants learned the arbitrary assignments of a set of stimuli to one of two response categories. Informative feedback was provided on less than 25% of the trials. During positive feedback blocks, half of the trials were eligible for informative feedback; of these, informative feedback was only provided when the response was correct. A similar procedure was used on negative feedback blocks, but here informative feedback was only provided when the response was incorrect. In this manner, we sought to identify regions that were differentially responsive to positive and negative feedback as well as areas that were responsive to both types of informative feedback. Several regions of interest, including the bilateral nucleus accumbens, caudate nucleus, anterior insula, right cerebellar lobule VI, and left putamen, were sensitive to informative feedback regardless of valence. In contrast, several regions were more selective to positive feedback compared to negative feedback. These included the insula, amygdala, putamen, and supplementary motor area. No regions were more strongly activated by negative feedback compared to positive feedback. These results indicate that the neural areas supporting associative learning vary as a function of how that information is learned. In addition, areas linked to intrinsic reinforcement showed considerable overlap with those identified in studies using extrinsic reinforcers.

Cholecystokinin is necessary for the expression of morphine conditioned place preference.

There is evidence that the neuropeptide cholecystokinin (CCK) is important for the rewarding effects of drugs of abuse. However, less is known regarding the role of CCK in drug seeking and craving. The present study investigated whether the CCK(B) antagonist L-365, 260 could block morphine-induced drug seeking using the conditioned place preference paradigm and whether the dopaminergic reward pathway contributes to the effect of L-365, 260 on expression of morphine place preference. We found that systemic administration of the CCK(B) antagonist L-365, 260 attenuates the expression of morphine-induced drug seeking as assessed using conditioned place preference (CPP) and shows that this effect is mediated by CCK(B) receptors in the anterior nucleus accumbens (NAcc). Additionally, we demonstrate that this effect is dependent on D(2) receptor activation in the anterior nucleus accumbens (NAcc). These results indicate that endogenous CCK modulates the incentive-salience of morphine-associated cues and suggest that CCK antagonists may be useful in the treatment of drug craving.