Indwelling Intravenous Catheter Research Articles

Ventilatory Effects of Fentanyl, Heroin, and d-Methamphetamine, Alone and in Mixtures in Male Rats Breathing Normal Air .

The number of drug overdoses and deaths has increased significantly over the past decade and co-use of opioids and stimulants is associated with greater likelihood of overdose and decreased likelihood of accessing treatment, compared with use of opioids alone. Potential adverse effects of opioid/stimulant mixtures, particularly methamphetamine, are not well characterized. Two structurally different drugs with agonist properties at µ-opioid receptors (MOR), fentanyl and heroin, and d-methamphetamine, alone and in mixtures, were assessed for their effects on ventilation in rats breathing normal air. Whole-body phethysmography chambers were equipped with a tower and swivel allowing infusions to indwelling intravenous catheters. After a 45-minute habituation period, saline, fentanyl, heroin, or d-methamphetamine, alone and in mixtures, was administered. Five minutes later, the opioid receptor antagonist naloxone or vehicle was injected. Fentanyl (0.0032-0.1 mg/kg) and heroin (0.32-3.2 mg/kg) decreased ventilation [frequency (f) and tidal volume (VT)] in a dose-related manner whereas d-methamphetamine (0.1-3.2 mg/kg) increased f to >400% of control and decreased VT to <60% of control, overall increasing minute volume (product of f and VT) to >240% of control. When combined, d-methamphetamine (0.1-3.2 mg/kg) attenuated the ventilatory depressant effects of fentanyl (0.1 mg/kg) and heroin (3.2 mg/kg). d-Methamphetamine did not alter the potency of naloxone to reverse the ventilatory depressant effects of fentanyl or heroin. These studies demonstrate that d-methamphetamine can attenuate the ventilatory depressant effects of moderate doses of opioid receptor agonists while not altering the potency of naloxone to reverse opioid hypoventilation. SIGNIFICANCE STATEMENT: Co-use of opioids and stimulants is associated with greater likelihood of overdose and decreased likelihood of accessing treatment, compared with use of opioids alone. Potential adverse effects of opioid/stimulant mixtures are not well characterized. This study reports that 1) d-methamphetamine attenuates the ventilatory depressant effects of moderate doses of two structurally different opioid receptor agonists, fentanyl and heroin, and 2) d-methamphetamine does not alter potency or effectiveness of naloxone to reverse the ventilatory depressant effects of these opioid receptor agonists.

Venous catheters in horses - early ultrasonographic venous abnormalities and evidence of biofilms

Complications associated with indwelling intravenous catheters vary from minor to severe. Changes in tissue architecture and vein structure may be detectable prior to clinical alterations. The aim of the study was to characterize and compare changes in a catheterized vein and surrounding tissue by clinical and ultrasonographic examination. Microbiological infestation of catheter specimens was assessed. In this prospective, observational, clinical study 55 horses with an indwelling intravenous catheter have been included. Subsequent to catheter placement, vein and surrounding tissue were daily examined clinically and by ultrasonographic examination at predetermined localizations. After sterile removal of the catheters, specimens underwent microbiological testing and scanning electron microscopy. Obtained data were analyzed via descriptive statistics. Thickness of the venous wall was compared at predetermined localizations and time points for several parameters with the help of non-parametric tests (level of significance at p < 0.05, post-hoc Bonferroni correction). Overall, in 41.8 % of the horses transient alterations (swelling) of the surrounding tissue occurred during catheterization. Median catheterization was 69.5 hours (19 hour-10 days). With ultrasonography, venous valves and collateral vessels could be detected reliably. Significant alterations in wall thickness during catheterization were associated with various factors (location site [p ≤ 0.001], season [p = 0.006], anesthesia [p ≤ 0.001]).Microbiological analysis revealed a positive result in 23.5 %, 12 of the 51 samples; raster electron microscopy showed presence of bacteria in 25.0 %, 4 of the 16 investigated catheter samples. Local tissue changes at the insertion site of the catheter are commonly associated with catheterization, and are easily detectable with ultrasonography. Despite the easy performance in a clinical setting, the benefit of routine ultrasonographic monitoring of catheterized veins might be questionable with regard to early identification and prediction of catheter-associated venous disease. Bacteria might be detectable morphologically on the catheter but frequently lack a positive result from standard bacterial cultivation.

201. An Exploration of Parent and Youth Roles in Diagnostic Testing for Growth Hormone Deficiency

Youth medical decision-making involvement has been explored with respect to treatment of chronic health conditions (e.g., type 1 diabetes) and is linked to greater treatment adherence and self-efficacy. However, little is known about youth’s role with respect to medical testing and diagnostic procedures. As part of the evaluation of short stature, youth may undergo stimulation tests that measure growth hormone (GH) secretory capacity to determine possible GH deficiency. Testing lasts about three hours and involves specialized nursing, an in-dwelling intravenous catheter (IV) for serial blood sampling, and two medications with potential side effects.

Strain and sex matters: Differences in nicotine self-administration between outbred and recombinase-driver transgenic rat lines.

Preclinical studies of nicotine self-administration provide important value for the field as they are highly rigorous, controlled, can be conducted quickly, and are generalizable to humans. Given the translational value of the nicotine self-administration model, and the relatively new guidelines of the National Institutes of Health to include sex as a biological variable, strain and sex differences in nicotine acquisition were examined here in two outbred rat strains. Sprague-Dawley (SD) and Long-Evans (LE; wildtype and cholinergic acetyltransferase cre-recombinase transgenic) rats of each sex were implanted with indwelling intravenous jugular catheters. Rats were trained to self-administer nicotine (0.02 mg/kg per infusion, paired with contingent light + tone stimuli). Acquisition criteria were set at a minimum active:inactive response ratio of 2:1 and a minimum of 10 infusions per session, both of which had to be met for a minimum of 10 sessions. Across 10 sessions, male SD rats self-administered significantly more nicotine than female SD rats (p < .05), indicating a sex difference in this strain. LE females self-administered more nicotine than SD females indicative of a strain difference between females (p < .05). SD males increased nicotine infusions across sessions compared to LE males and SD females (p < .05). No strain or sex differences were observed in the number of sessions to reach criteria. No differences between wildtype and transgenic LE rats were observed. These results demonstrate sex and strain differences in nicotine self-administration between SD and LE rats and may lend insight into development of other nicotine self-administration models, where sex and strain may impact acquisition. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Lutetium-177 DOTATATE Therapy Is Associated With Biochemical Endocrine Abnormalities in the Immediate Post-Treatment Period

Abstract Introduction: Lutetium-177(177Lu) DOTATATE is a form of peptide receptor radionuclide therapy (PRRT) targeting somatostatin receptor-2 (SSTR2), that is utilized in the treatment of neuroendocrine tumors. As various endocrine glands express SSTR2, 177Lu-DOTATATE can potentially disrupt endocrine function. The immediate post-treatment effects of 177Lu-DOTATATE on endocrine function are not known. Methods: We performed a retrospective analysis of data obtained from patients (≥18 years) enrolled under the 177Lu-DOTATATE trial (NCT03206060) for treatment of SSTR2 positive inoperable/metastatic pheochromocytoma/paraganglioma. 177Lu-DOTATATE (200 mCi) was administered intravenously every 8 weeks, for a total of 4 cycles. Endocrine evaluation was performed on blood samples obtained through an indwelling intravenous catheter during each cycle of PRRT on day 1 (pre-PRRT), day 2 (post-PRRT day 1), day 3 (post-PRRT day 2), day 30 (post-PRRT day 29), and day 60 (day 1 of the next cycle). Hormonal evaluation included ACTH, cortisol, TSH, free T4, GH, FSH, LH, testosterone, estradiol, and prolactin. Baseline abnormal hormonal values, and gonadotrophs in premenopausal women were excluded. Results: Data from 27 subjects (age: 54 ± 12.7 years; 13 female, 14 male) were analyzed. Three out of 27 patients (11.1%) developed clinically significant persistent endocrinopathies - secondary adrenal insufficiency (AI): (n=1 male), primary hypothyroidism: (n=1 male) and hypergonadotropic hypogonadism: (n=1 female). Compared to day 1, there were significant reductions in 1) ACTH (pg/mL) levels on day 2 (36.8 ± 34.1 vs. 23.1 ± 21; p&amp;lt;0.0001), day 3 (36.8 ± 34.1 vs. 24.3 ± 19.4; p&amp;lt;0.0001), and day 30 (36.8 ± 34.1 vs. 27.7 ± 19.1; p=0.01), without significant changes in average cortisol level, apart from 1 patient with undetectable cortisol, who developed secondary AI after 2nd cycle 2) LH (IU/L) levels on day 3 (16.4 ± 13.5 vs. 15.4 ± 13.5; p=0.014), 3) prolactin (ng/mL) on day 2 (9.9 ± 7.0 vs. 7.1 ± 5.7; p&amp;lt;0.0001), day 3 (9.9 ± 7.0 vs. 7.1 ± 5.4; p&amp;lt;0.0001), and day 30 (9.9 ± 7.0 vs. 7.6 ± 5.7; p=0.005), without significant changes in average estrogen and testosterone levels, apart from 1 woman with low estrogens developing hypergonadotropic hypogonadism after 3rd cycle 4) TSH (microIU/L) on day 2 (2.2 ± 1.4 vs. 1.4 ± 0.9; p&amp;lt;0.0001), and day 3 (2.2 ± 1.4 vs. 1.7 ± 1.3; p=0.001), and 5) free T4 (ng/dL) on day 2 (1.1 ± 0.2 vs. 1 ± 0.2; p=0.002). Hormonal values on day 60 were not significantly different from those on day 1, suggesting that majority of these changes were transient. Conclusions:177Lu-DOTATATE can be associated with transient endocrine disruption in the immediate post-treatment period. However, some of these changes may lead to persistent endocrinopathies which are likely associated with radiation exposure to the tissues expressing SSTR2. It is therefore important to periodically assess endocrine function during PRRT.

Delay Discounting of Cocaine‐Food Choice in Socially Housed Female and Male Cynomolgus Macaques

At present, there are no FDA-approved pharmacological treatments for cocaine use disorders (CUD). Because there is evidence of sex differences in vulnerability to cocaine abuse (O’Brien and Anthony, 2005) and treatment outcomes (Sugarman et al., 2017), research needs to include both sexes in evaluating treatment strategies. Weafer and de Wit (2014) have suggested that impulsivity is a stronger predictor of drug abuse in females compared to males and lack of inhibitory control may be a mechanism mediating the faster progression of drug use in women compared to men. The overarching goal of the present research is to utilize a “personalized medicine” approach to evaluating the role of environmental and pharmacological interventions on the reinforcing effects of cocaine. In this study, socially housed female (N=5) and male (N=6) cynomolgus monkeys, each implanted with an indwelling intravenous catheter and self-administering cocaine (0.01-0.1 mg/kg/injection) under a concurrent schedule with food (1.0-g banana-flavored pellets) as the alternative, served as subjects. Under these conditions, the frequency of cocaine choice increases in a dose-dependent manner, from <20% choice when 0.01 mg/kg/injection cocaine was available as an alternative to food, to >80% choice when 0.1 mg/kg/injection was the alternative to food; in this preliminary study, no sex or social rank differences were noted. Next, environmental manipulations were studied at both ends of the cocaine dose-response curve in order to assess whether there were sex differences in sensitivity to the reinforcing effects of cocaine. To study impulsivity, we used a delay discounting procedure similar to that described by Woolverton and colleagues (Huskinson et al., 2015, 2016). Differences in sensitivity to changes in cocaine preference when the preferred cocaine dose was available would provide information as to potential sex differences in the reinforcing strength of cocaine. In contrast, when low, non-preferred, cocaine doses were studied and food reinforcement was delayed, sex differences would provide information related to sensitivity of adverse environmental changes on vulnerability to cocaine abuse. In preliminary findings, when delays were imposed on high-dose cocaine, the indifference points (IP; 50% choice between cocaine and food) were not different between males and females (168.88 ± 75.6 seconds vs. 154.94 ± 39.1 seconds, respectively). However, when low-dose cocaine was available and food reinforcement was delayed, males were more sensitive to changes in the environment, as represented by lower IP values (46.74 ± 16.8 seconds vs. 114.39 ± 44.9 seconds, respectively). Studies are currently underway to determine if pharmacological manipulations, with and without delays, would provide additional reductions in cocaine choice, at both ends of the cocaine dose-response curve. An interesting behavioral pharmacology study would involve examine drug effects under conditions in which delayed high-dose cocaine and food-delayed low-dose cocaine produce similar behaviors (i.e., % cocaine choice).

Venous blood gas parameters, electrolytes, glucose and lactate concentration in sick neonatal foals: Direct venipuncture versus push-pull technique.

Blood collection by indwelling intravenous catheter (IVC) avoids repeated venipuncture, which could cause thrombophlebitis risk, anxiety and pain in patients. To compare blood gas parameters, electrolytes, glucose, lactate and haematocrit concentration obtained from venous blood samples collected via a jugular IVC by push-pull (PP) technique to those obtained by venipuncture in hospitalised foals, at the time of catheter placement (T0) and 24hours after the beginning of intravenous therapy (T24). Prospective observational study. Paired blood samples were drawn from hospitalised foals at T0 and T24. In each foal, one venous blood sample was collected via IVC by the following PP technique: 2.4mL of blood was aspirated and immediately reinfused through the catheter three times consecutively, then 1mL of blood was collected using a 1mL heparinised syringe. Thereafter, another sample was collected by direct venipuncture of the contralateral jugular vein, with an identical 1mL heparinised syringe, with a 1-inch, 20-G needle. All samples were analysed with an automated blood gas analyser within 10minutes of collection. The agreement between the two techniques was assessed by Bland-Altman analysis and intraclass correlation coefficient (ICC). The level of agreement of blood gas values obtained by the two different techniques was high with very small bias and clinically acceptable ICC (>0.907 at T0; >0.794 at T24) for all variables, except for haematocrit (bias -3.52 at T0; -2.44 at T24) and PvO2 at T0 and T24 (ICC 0.669 and 0.733, respectively). Potential sub-clinical catheter-related complications were not investigated by ultrasound or bacterial culture of the catheter; short duration of the study. PP technique appears to be acceptable for collection of blood samples for venous blood gas parameters, as well as electrolytes, glucose and lactate in sick neonatal foals.

MON-214 Biochemical Abnormalities in Endocrine Function Associated with Lutetium 177-DOTATATE Therapy in Metastatic Pheochromocytoma and Paraganglioma

Background: Lutetium-177 (177Lu) DOTATATE (Lutathera ®) is a form of peptide receptor radionuclide therapy (PRRT) that has shown efficacy in the treatment of neuroendocrine tumors through its action on somatostatin receptor 2. The effects of Lutathera on endocrine function in metastatic pheochromocytoma and paraganglioma (PPGL) has not been evaluated. Methods: We performed a prospective analysis on 21 patients (10 female, 11 male) with metastatic PPGL receiving 177Lu DOTATATE (NCT03206060) at our center from July 2017 to August 2019. Hormonal evaluation was obtained 24 and 48 hours after each 177Lu DOTATATE administration and 4 weeks ± 1 week after each cycle to assess for biochemical endocrine abnormalities (BEAs). Blood samples were obtained after 30 minutes of resting with an in-dwelling intravenous catheter. We excluded BEAs that were present either prior to the initiation of 177Lu DOTATATE or due to a pre-existing endocrine disorder. Results: We observed BEAs in 18 of 21 (85.7%, 7 female, 11 male) patients. BEAs most commonly involved the pituitary-adrenal axis [ACTH (N: 5-46 pg/mL): 6/21 (28.5%, 5 high, 1 low); serum cortisol (N: 5-25 mcg/dL): 5/21 (23.8%, 2 high, 3 low)], followed by pituitary-thyroid axis [TSH (N: 0.27-4.2 IU/mL): 6/21 (28.5%, 4 high, 2 low); free thyroxine (N: 0.9-1.7 ng/dL): 2/21 (9%, 0 high, 2 low)], pituitary-gonadal axis [FSH (N: 1-11 U/L): 2/21 (9%, 1 high, 1 low); LH (1-8 U/L): 1/21 (5%, 0 high, 1 low); total testosterone (N: 262-1593 ng/dL): 4/21 (19%, 0 high, 4 low)]; and growth hormone [3/21 (N: 0 - 3 ng/mL): (14.3%, 3 high, 0 low)]. Of the 28 observed BEAs, 17/28 (61%) were initially noted during cycle 1, 7/28 (25%) during cycle 2, and 4/28 (14%) during cycle 3, and 16/28 (57%) were noted within 48 hours of 177Lu DOTATATE injection. There was no significant association between the standardized uptake values of adrenals (p=0.28), pituitary (p=0.75), and thyroid gland (p=0.61) on the baseline diagnostic 68Ga DOTATATE scan and their respective BEAs. One patient developed overt hypothyroidism and was started on levothyroxine, and another patient developed central adrenal insufficiency likely from immunotherapy started after 177Lu DOTATATE therapy. In all other patients, BEAs were transient and spontaneously resolved. Limitations included the observational nature of the study, lack of data on levels of IGF-1, parathyroid hormone, or hemoglobin A1C. Conclusion:177Lu DOTATATE therapy for metastatic PPGL is associated with biochemical abnormalities in endocrine function. Although mostly transient, there is a potential risk for BEAs to be permanent and to manifest clinically. Therefore, serial monitoring of abnormal hormonal values is necessary and treatment should be considered when appropriate. Studies on larger populations with long-term follow-up are necessary to further investigate the incidence of endocrine abnormalities with 177Lu DOTATATE therapy.

Candida Bloodstream Infection: Changing Pattern of Occurrence and Antifungal Susceptibility over 10 Years in a Tertiary Care Saudi Hospital.

Background Candida has emerged as one of the most important pathogens that cause bloodstream infection (BSI).Understanding the current Candida BSI trends, the dominant species causing disease and the mortality associated with this infection are crucial to optimize therapeutic and prophylaxis measures. Objectives To study the epidemiology and to evaluate the risk factors, prognostic factors, and mortality associated with candidemia and to compare these findings with previously published studies from Saudi Arabia. Design A retrospective medical record review. Setting Tertiary hospital in Riyadh. Patients and Methods The analysis included all cases of Candida blood stream infection who are >18 years old over the period from 2013 to 2018. Continuous variables were compared using the parametric T-test while categorical variables were compared using the Chi-squared test. Main Outcome Measure Incidence, resistance, and hospital outcomes in Candida blood stream infection. Sample Size 324 patients. Results Three hundred and twenty-four episodes of Candida blood stream infections were identified. Median age of patients was 49.7 SD ± 28.1 years, and 53% of patients were males. More than half of the patients had an underlying disease involving the abdomen or laparotomy, 78% had an indwelling intravenous catheter, and 62% had suffered a bacterial infection within 2 weeks prior to candidemia. Candida albicans represents 33% of all isolates with decreasing trend overtime. There was an increase in the number of nonalbicans Candida overtime with Candida tropicalis in the lead (20%). Use of broad spectrum antibiotics (82%), prior ICU admission (60%) and use of central venous catheters (58%) were the most prevalent predisposing factors of candidemia. Azole resistance was variable overtime. Resistance to caspofungin remained very low (1.9%). Fourteen days crude mortality was 37% for ICU patients and 26.7% in non-ICU patients, while hospital crude mortality was 64.4% and 46.7%, respectively. Conclusion There is an increasing trend of nonalbicans Candida blood stream infection. Fluconazole resistance remained low to C. albicans. Most isolates remain susceptible to caspofungin, voriconazole, and amphotericin B. Candida bloodstream infection is associated with high 14-day hospital mortality.

Effects of early life stress on cocaine self-administration in post-pubertal male and female rhesus macaques.

Early life stress (ELS), including childhood maltreatment, is a predictive factor for the emergence of cocaine use disorders (CUDs) in adolescence. Accordingly, we examined whether post-pubertal male and female rhesus macaques that experienced infant maltreatment (maltreated, n = 7) showed greater vulnerability to cocaine self-administration in comparison with controls (controls, n = 7). Infant emotional reactivity was measured to assess differences in behavioral distress between maltreated and control animals as a result of early life caregiving. Animals were then surgically implanted with indwelling intravenous catheters and trained to self-administer cocaine (0.001-0.3mg/kg/infusion) under fixed-ratio schedules of reinforcement. Days to acquisition, and sensitivity to (measured by the EDMax dose of cocaine) and magnitude (measured by response rates) of the reinforcing effects of cocaine were examined in both groups. Maltreated animals demonstrated significantly higher rates of distress (e.g., screams) in comparison with control animals. When given access to cocaine, control males required significantly more days to progress through terminal performance criteria compared with females and acquired cocaine self-administration slower than the other three experimental groups. The dose that resulted in peak response rates did not differ between groups or sex. Under 5-week, limited-access conditions, males from both groups had significantly higher rates of responding compared with females. In control monkeys, these data support sex differences in cocaine self-administration, with females being more sensitive than males. These findings also suggest that ELS may confer enhanced sensitivity to the reinforcing effects of cocaine, especially in males.

Roseomonas mucosa bacteremia in a neutropenic child: A case report and literature review.

Roseomonas species is rarely found to be pathogenic to humans and there are few clinical cases that have been described in the literature. We report a case of Roseomonas mucosa bacteremia that involved a 9-year-old Japanese boy who was in a condition of febrile neutropenia caused by chemotherapy for cerebellar medulloblastoma. Conventional phenotyping failed to identify the organism; however, genetic analysis using 16S rDNA sequencing confirmed the pathogen to be R. mucosa. The patient recovered following treatment by meropenem without any complications. A literature review of pediatric cases of Roseomonas bacteremia identified 12 other documented cases, and these revealed that a common clinical situation for the infection is an immunocompromised state with malignancy and/or an indwelling intravenous catheter. Because of the low number of cases, the overall picture of Roseomonas bacteremia in children remains to be elucidated; however, the prognosis of the infection appears to be satisfactory.

Comparison of two blood sampling techniques for the determination of coagulation parameters in the horse: Jugular venipuncture and indwelling intravenous catheter

Evaluation of coagulation status is an important component of critical care. Ongoing monitoring of coagulation status in hospitalised horses has previously been via serial venipuncture due to concerns that sampling directly from the intravenous catheter (IVC) may alter the accuracy of the results. Adverse effects such as patient anxiety and trauma to the sampled vessel could be avoided by the use of an indwelling IVC for repeat blood sampling. To compare coagulation parameters from blood obtained by jugular venipuncture with IVC sampling in critically ill horses. Prospective observational study. A single set of paired blood samples were obtained from horses (n = 55) admitted to an intensive care unit by direct jugular venipuncture and, following removal of a presample, via an indwelling IVC. The following coagulation parameters were measured on venipuncture and IVC samples: whole blood prothrombin time (PT), fresh plasma PT and activated partial thromboplastin time (aPTT) and stored plasma antithrombin activity (AT) and fibrinogen concentration. D-dimer concentration was also measured in some horses (n = 22). Comparison of venipuncture and IVC results was performed using Lin's concordance correlation coefficient. Agreement between paired results was assessed using Bland Altman analysis. Correlation was substantial and agreement was good between sample methods for all parameters except AT and D-dimers. Each coagulation parameter was tested using only one assay. Sampling was limited to a convenience sample and timing of sample collection was not standardised in relation to when the catheter was flushed with heparinised saline. With the exception of AT and D-dimers, coagulation parameters measured on blood samples obtained via an IVC have clinically equivalent values to those obtained by jugular venipuncture.

Mycobacterium abscessus causing native valve endocarditis due to peripherally inserted central catheter line

Infections due to rapidly-growing mycobacteria (RGM) are increasing worldwide, especially in immunocompromised hosts. However, data on the clinical features of patients with RGM bacteremia are limited [1]. Data on the incidence of clinically significant non-tuberculous mycobacteria (NTM) infections from India are scarce as these are frequently under-diagnosed due to either under recognition by clinicians because of the nonspecific nature of their clinical manifestations, and/or the inadequacy of laboratory services [2].We present a case of Mycobacterium abscessus native tricuspid valve endocarditis in a patient who had a peripherally inserted central catheter line (PICC).Clinicians need to be aware of RGM as a cause of prolonged fever in patients who have chronic indwelling intravenous catheters [3].

Development of a translational model to screen medications for cocaine use disorder I: Choice between cocaine and food in rhesus monkeys

BackgroundHomologous cocaine self-administration procedures in laboratory animals and humans may facilitate translational research for medications development to treat cocaine dependence. This study, therefore, sought to establish choice between cocaine and an alternative reinforcer in rhesus monkeys responding under a procedure back-translated from previous human studies and homologous to a human laboratory procedure described in a companion paper. MethodsFour rhesus monkeys with chronic indwelling intravenous catheters had access to cocaine injections (0, 0.043, 0.14, or 0.43mg/kg/injection) and food (0, 1, 3, or 10 1g banana-flavored food pellets). During daily 5h sessions, a single cocaine dose and a single food-reinforcer magnitude were available in 10 30-min trials. During the initial “sample” trial, the available cocaine and food reinforcer were delivered non-contingently. During each of the subsequent nine “choice” trials, responding could produce either the cocaine or food reinforcer under an independent concurrent progressive-ratio schedule. ResultsPreference was governed by the cocaine dose and food-reinforcer magnitude, and increasing cocaine doses produced dose-dependent increases in cocaine choice at all food-reinforcer magnitudes. Effects of the candidate medication lisdexamfetamine (0.32–3.2mg/kg/day) were then examined on choice between 0.14mg/kg/injection cocaine and 10 pellets. Under baseline conditions, this reinforcer pair maintained an average of approximately 6 cocaine and 3 food choices. Lisdexamfetamine dose-dependently decreased cocaine choice in all monkeys, but food choice was not significantly altered. ConclusionsThese results support utility of this procedure in rhesus monkeys as one component of a platform for translational research on medications development to treat cocaine use disorder.

MYROIDES INFECTION IN A BABOON AFTER PROLONGED PIG KIDNEY GRAFT SURVIVAL.

Immunosuppressed patients and experimental nonhuman primates are at risk of opportunistic infection. We report a Myroides spp infection in an immunosuppressed baboon that had received a life-supporting kidney from a genetically-engineered pig. The baboon received a costimulation blockade-based immunosuppressive regimen as well as two anti-inflammatory agents (tocilizumab and etanercept). Although the pig kidney functioned well, approximately four months after the transplant the baboon became less active and ate and drank poorly. On day 136, it collapsed and died despite inotropic and fluid support. A blood culture drawn before death grew Myroides spp. To our knowledge, Myroides spp has not been reported as a cause of opportunistic infection in either patients with organ allotransplants or experimental animals. We summarize what is known about this rare organism, and suggest it should be considered in any immunocompromised patient or animal. In the present case, we suggest the baboon died of circulatory shock following infection through an indwelling intravenous catheter.

Plasmatic hypercoagulation in patients with breast cancer

Breast cancer is an important health threat to women worldwide, and is associated with a 9-14% incidence of thrombophilia. Of interest, patients with breast cancer have been noted to have an increase in endogenous carbon monoxide production via upregulation of heme oxygenase-1 activity. Given that it has been demonstrated that carbon monoxide enhances plasmatic coagulation in vitro and in vivo, we sought to determine whether patients with breast cancer had an increase in endogenous carbon monoxide and concurrent plasmatic hypercoagulability. Breast cancer patients who were not smokers scheduled to undergo partial or complete mastectomy (n = 18) had 15 ml of whole blood collected via an indwelling intravenous catheter and anticoagulated with sodium citrate. Whole blood was centrifuged and citrated plasma assessed with a thromboelastometric method to measure coagulation kinetics and the formation of carboxyhemefibrinogen. Breast cancer patients were determined to have an abnormally increased carboxyhemoglobin concentration of 2.5 ± 1.3%, indicative of heme oxygenase-1 upregulation. Breast cancer patient plasma on average clotted 73% more quickly and had 32% stronger thrombus strength than normal individual (n = 30) plasma. Further, 44% of breast cancer patients had plasma clot strength that exceeded the 95% confidence interval value observed in normal individuals, and 75% of this hypercoagulable subgroup had carboxyhemefibrinogen formation. Future investigation of the role played by heme oxygenase-1-derived carbon monoxide in the pathogenesis of breast cancer-related thrombophilia is warranted.

Current approaches to the laboratory assessment of abuse potential

Current approaches to the laboratory assessment of abuse potential

Endothelial-Like Progenitor Cells Engineered to Produce Prostacyclin Rescue Monocrotaline-Induced Pulmonary Arterial Hypertension and Provide Right Ventricle Benefits

Intravenous prostacyclin is approved for treating pulmonary arterial hypertension (PAH), but it has a short half-life and must be delivered systemically via an indwelling intravenous catheter. We hypothesize that localized jugular vein delivery of prostacyclin-producing cells may provide sustained therapeutic effects without the limitations of systemic delivery. We generated a vector expressing a human cyclooxygenase isoform 1 and prostacyclin synthase fusion protein that produces prostacyclin from arachidonic acid. Endothelial-like progenitor cells (ELPCs) were transfected with the cyclooxygenase isoform 1-prostacyclin synthase plasmid and labeled with lentivirus expressing nuclear-localized red fluorescent protein (nuRFP). The engineered ELPCs (expressing cyclooxygenase isoform 1-prostacyclin synthase and nuRFP) were tested in rats with monocrotaline (MCT)-induced PAH. In PAH prevention studies, treatment with engineered ELPCs or control ELPCs (expressing nuRFP alone) attenuated MCT-induced right ventricular systolic pressure increase, right ventricular hypertrophy, and pulmonary vessel wall thickening. Engineered ELPCs were more effective than control ELPCs in all variables evaluated. In PAH reversal studies, engineered ELPCs or control ELPCs increased the survival rate of rats with established PAH and decreased right ventricular hypertrophy. Engineered ELPCs provided a survival benefit 2 weeks earlier than did control ELPCs. Microarray-based gene ontology analysis of the right ventricle revealed that a number of MCT-altered genes and neurotransmitter pathways (dopamine, serotonin, and γ-aminobutyric acid) were restored after ELPC-based prostacyclin gene therapy. Cyclooxygenase isoform 1-prostacyclin synthase-expressing ELPCs reversed MCT-induced PAH. A single jugular vein injection offered survival benefits for at least 4 weeks and may provide a promising option for PAH patients.

EXAMINING THE RELATIONSHIP BETWEEN COCAINE AND SLEEP IN A MONKEY MODEL OF DRUG ABUSE

Clinical literature suggests that sleep deprivation can induce patients to relapse to drug taking. This animal study examined the effects of cocaine (COC) self‐administration on several sleep measures and how sleep disruption affects COC preference. Subjects were 8 adult male rhesus monkeys (Macaca mulatta), each wearing Actical activity monitors on their collar and surgically implanted with an indwelling intravenous catheter for COC self‐administration. Baseline activity was monitored for 1 week in the absence of any behavioral testing. Each morning (0730), monkeys were permitted to respond under choice procedure in which food reinforcement (three, 1‐g banana‐flavored pellets) was contingent upon completing the response requirement on one lever, while COC (0.003–0.1 mg/kg/injection) or saline presentation was contingent on responding on the other lever. After baseline cocaine‐choice curves were determined, the monkeys were sleep disrupted. Our results indicate that COC self‐administration causes significant changes on several sleep measures, providing evidence for possible treatment strategies. We also found that sleep disruption caused significant changes on sleep measures but did not alter the reinforcing strength of COC the next morning. Future studies will examine a medication that may enhance sleep (quetiapine) and may also decrease COC self‐administration. DA025120

Blood alcohol concentrations rise rapidly and dramatically after Roux-en-Y gastric bypass

BackgroundThis study provides new information on how rapidly and extensively alcohol is absorbed after Roux-en-Y gastric bypass (RYGB). Previous alcohol pharmacokinetic research in RYGB patients has not reported blood alcohol concentrations in this early time period after ingestion. The objective of this study was to examine the rate and extent of alcohol absorption, particularly in the first 10 minutes after a dose of alcohol. MethodsFive female participants who had undergone RYGB 3 to 4 years previously completed the study. Participants were given .3 g/kg of actual weight of ethanol. After the dose of alcohol, blood samples were collected through an indwelling intravenous catheter every minute for the first 5 minutes and at 7.5, 10, 20, and 60 minutes. ResultsThe observed mean Cmax was 138.4±28.6 mg/dL (range 98.0–170.0 mg/dL), and the observed mean Tmax was 5.4±3.1 minutes (range 2–10 minutes) after alcohol consumption. ConclusionsWithin minutes after consumption of a beverage containing a modest amount of alcohol, post-RYGB patients achieve disproportionately high blood alcohol concentrations. All 5 participants in this study reached blood alcohol concentrations>.08%, the legal driving limit in the United States, within 10 minutes after a dose of alcohol. Clinicians are encouraged to educate patients about the marked changes in alcohol pharmacokinetics that are they are likely to experience after RYGB and to guide patients in making modifications to alcohol intake after surgery accordingly.