Correlation between Venous Thromboembolism Risk and Venous Congestion in Microvascular Reconstruction of the Lower Extremity.

BACKGROUND: Risk for venous thromboembolism formation and the relationship to postoperative free flap venous congestion and flap failure have not been adequately evaluated in a trauma population. The authors aim to use the Caprini Risk Assessment Model to evaluate the association between venous thromboembolism risk and postoperative flap venous congestion following lower extremity free tissue transfer. METHODS: A retrospective analysis was conducted of all patients who underwent lower extremity free flap reconstruction of traumatic defects at a single institution between 2007 and 2016. A Wilcoxon rank sum test was used for nonparametric analysis of aggregate Caprini Risk Assessment Model scores and flap outcomes. Flap venous congestion and failure rates as associated with the categorical variables underlying the Caprini Risk Assessment Model were further studied. Logistic regression was used to evaluate each of these outcomes and other flap-related covariates relative to the Caprini Risk Assessment Model categorical variables that had the greatest effect on our patient sample. RESULTS: One hundred twelve patients underwent lower extremity free flap reconstruction. One hundred eight free flaps were analyzed. Eight patients were excluded. The majority of patients were male (75.9 percent) and required reconstruction because of acute trauma (68.1 percent versus 31.9 percent for chronic wounds). There was no statistically significant association found between age, body mass index, or timing of trauma versus venous congestion, flap failure, or other flap-related covariates. CONCLUSION: In patients with significantly elevated Caprini Risk Assessment Model scores, there was no significant association between venous thromboembolism risk and flap failure following free tissue reconstruction of lower extremities. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

The effects of amphetamine, butorphanol, and their combination on cocaine self-administration.

There have been recent calls to examine the efficacy of drug-combination therapies in the treatment of substance use disorders. The purpose of the present study was to examine the ability of a novel stimulant-opioid combination to reduce cocaine self-administration, and to compare these effects to those of each drug administered alone. To this end, male Long-Evans rats were implanted with intravenous catheters and trained to self-administer cocaine under positive reinforcement contingencies. Once self-administration was acquired, rats were divided into four different groups and treated chronically for 20 days with (1) saline, (2) the psychomotor stimulant and monoamine releaser amphetamine, (3) the mu/kappa opioid agonist butorphanol, or (4) a combination of amphetamine and butorphanol. During chronic treatment, cocaine self-administration was examined on both fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. On the FR schedule, butorphanol significantly decreased cocaine self-administration, but this effect was not enhanced by amphetamine. On the PR schedule, amphetamine and butorphanol non-significantly decreased cocaine self-administration when administered alone but significantly decreased cocaine self-administration when administered in combination. These data suggest that under some conditions (e.g., when the response requirement of cocaine is high), a dual stimulant-opioid pharmacotherapy may be more effective than a single-drug monotherapy.

Access to a running wheel decreases cocaine-primed and cue-induced reinstatement in male and female rats.

BACKGROUND: Relapse to drug use after a period of abstinence is a persistent problem in the treatment of cocaine dependence. Physical activity decreases cocaine self-administration in laboratory animals and is associated with a positive prognosis in human substance-abusing populations. The purpose of this study was to examine the effects of long-term access to a running wheel on drug-primed and cue-induced reinstatement of cocaine-seeking behavior in male and female rats. methods: Long-Evans rats were obtained at weaning and assigned to sedentary (no wheel) and exercising (access to wheel) groups for the duration of the study. After 6 weeks, rats were implanted with intravenous catheters and trained to self-administer cocaine for 14 days. After training, saline was substituted for cocaine and responding was allowed to extinguish, after which cocaine-primed reinstatement was examined in both groups. Following this test, cocaine self-administration was re-established in both groups for a 5-day period. Next, a second period of abstinence occurred in which both cocaine and the cocaine-associated cues were withheld. After 5 days of abstinence, cue-induced reinstatement was examined in both groups. RESULTS: Sedentary and exercising rats exhibited similar levels of cocaine self-administration, but exercising rats responded less than sedentary rats during extinction. In tests of cocaine-primed and cue-induced reinstatement, exercising rats responded less than sedentary rats, and this effect was apparent in both males and females. CONCLUSIONS: These data indicate that long-term access to a running wheel decreases drug-primed and cue-induced reinstatement, and that physical activity may be effective at preventing relapse in substance-abusing populations.

TPH2 in the ventral tegmental area of the male rat brain.

This study surveyed the distribution of tryptophan hydroxylase 2 (TPH2) mRNA, protein, and enzymatic activity throughout the male Sprague-Dawley rat brain. TPH2 is the genetic isoform of TPH that catalyzes the rate-limiting step in serotonin biosynthesis within the central nervous system. Although cell bodies of serotonergic neurons are located mainly in the raphe, serotonin-containing axons innervate many regions of the brain. In the present study, we assessed the levels of mRNA, protein expression, and enzyme activity of TPH2 in the rat raphe, ventral tegmental area (VTA), substantia nigra, hippocampus, cerebellum, dorsal striatum, nucleus accumbens, amygdala, and medial prefrontal cortex to more fully understand the distribution of this enzyme throughout the central nervous system. The pineal gland was used as a control tissue that expresses TPH1 (the peripheral enzyme), but not TPH2. As expected, the raphe showed the highest brain TPH2 activity and protein expression. In the contrast to other reports, however, the VTA followed the raphe as the region with the second-highest amount of TPH2 activity, mRNA and protein expression. There were significantly lower TPH activities and levels of TPH2 protein in the other regions. In addition, TPH2 immunocytochemistry demonstrated the presence of TPH-positive cell bodies within the VTA. The results of this study indicate that TPH2 and serotonergic signaling may play an important role in the mesolimbic/mesocortical reward pathway.