BACKGROUND:

Ukraine's HIV epidemic, primarily affecting people who inject drugs (PWID), is expanding and transitioning despite free opioid substitution therapy (OST) and antiretroviral therapy (ART), two effective ways to reduce HIV transmission. Police detention of PWID not resulting in a formal charge or imprisonment is common, but its prevalence and impact on health are not known.

METHOD:

HIV-infected individuals (N=97) released from prison within one year were recruited and surveyed in two HIV-endemic Ukrainian cities about post-release police detention experiences. Data on the frequency of police detention, related adverse events, and impact on OST and ART continuity were collected, and correlates of detention were examined using logistic regression.

RESULTS:

Detention responses were available for 94 (96.9%) participants, of which 55 (58.5%) reported police detentions (mean=9.4 per person-year). For those detained while prescribed OST (N=28) and ART (N=27), medication interruption was common (67.9% and 70.4%, respectively); 23 of 27 participants prescribed OST (85.2%) were detained en route to/from OST treatment. Significant independent correlates of detention without charges included post-release ART prescription (AOR 4.98, p=0.021), current high-risk injection practices (AOR 5.03, p=0.011), male gender (AOR 10.88, p=0.010), and lower lifetime months of imprisonment (AOR 0.99, p=0.031).

CONCLUSIONS:

HIV-infected individuals recently released from prison in Ukraine experience frequent police detentions, resulting in withdrawal symptoms, confiscation of syringes, and interruptions of essential medications, including ART and OST. Structural changes are urgently needed to reduce police detentions in order to control HIV transmission and improve both individual and public health.

BACKGROUND:

Nicotine's acute effects on enhancing reinforcement from sensory rewards, shown in animal models, appear to occur with smoking in humans. These effects may vary due to reinforcer magnitude and amount of acute smoke intake (dose).

METHODS:

In a fully within-subjects design, dependent smokers (n=23) participated in 3 sessions. Each session followed overnight abstinence and involved 4 trials to assess responding via progressive ratio (PR 50%) for sensory reinforcement from high, moderate, or low preference music, or no reward (counter-balanced, 30-s/reinforcer). Sessions differed in smoking prior to each trial: 8 puffs on arrival and 2 puffs/trial ("8+2″), 2 puffs/trial only ("0+2″), or no smoking. Puffs were consumed via CReSS (Clinical Research Support System) to control topography, and smoking involved own brand to ensure palatability and increase generalizability of results.

RESULTS:

Reinforced responding was influenced by main effects of smoking condition (p<.05) and music reward type (p<.001). Compared to no smoking, responding for music was increased after smoking 8+2/trial puffs (p<.005), but not after 0+2/trial puffs. Smoking condition significantly increased reinforced responding only for the high preference music (p=.01), and not for moderate or low preference music, or for no reward. Withdrawal did not differ between the two smoking sessions, ruling out withdrawal relief as an explanation for differential reinforcement enhancement.

CONCLUSIONS:

Our findings confirm that just one cigarette after abstinence is sufficient for reinforcement enhancing effects and suggest that such enhancement is greater as magnitude of a reward's reinforcing efficacy increases.

A retrospective review was performed on patients with stable melanoma brain metastases treated with HD IL-2 therapy (720,000 IU/kg per dose intravenously; 14 doses, 2 cycles per course, maximum 2 courses) from January 1999 to June 2011 at Saint Louis University. There were 5 men and 3 women; median age was 52.2 years (26.8-61.1 years). One patient started treatment with lung lesions only (after resection of melanoma brain disease) and experienced partial response. Seven patients had brain metastases at treatment initiation. Median overall survival (mOS) for entire cohort (n = 8) was 8.7 months (2.1 to 19.0 months). All patients with brain metastases at first dose (n = 7) showed progressive disease; mOS was 6.7 months (range 2.1-18.2 months) for this group. Patients received radiosurgery and whole brain radiation before and after HD IL-2 therapy. One patient had symptoms suggestive of neurotoxicity. A history of alcohol abuse was revealed during admission. The patient's symptoms improved with initiation of an alcohol withdrawal protocol. In this analysis, patients with melanoma brain metastases received HD IL-2 without treatment-related mortality. We think that HD IL-2 should be considered as a treatment option in patients with melanoma brain metastases who are otherwise eligible for therapy.

The present study was designed to clarify the effect of chronic treatment with ethanol on the sensitization to hyperlocomotion induced by morphine in mice. After 3 days of withdrawal from a 3% ethanol diet for 5 days, the administration of a single dose of morphine (5 mg/kg, s.c.) to mice, which had recovered from withdrawal signs, significantly enhanced locomotor activity. Moreover, the release of dopamine in the nucleus accumbens induced by morphine (5 mg/kg, s.c.) was also enhanced by withdrawal for 3 days after treatment with 3% ethanol for 5 days. Under these conditions, chronic treatment with 3% ethanol for 5 days caused the up-regulation of KCC2 levels in the lower midbrain including the ventral tegmental area. Furthermore, the enhanced morphine-induced hyperlocomotion after chronic treatment with ethanol was significantly inhibited by the KCC2 inhibitor furosemide. These results suggest that chronic treatment with ethanol induces amenability to excitation of the mesolimbic dopamine system, which is mediated by increased protein levels of KCC2. These changes induced by ethanol may influence the susceptibility to drug dependence. Synapse, 2013. © 2013 Wiley Periodicals, Inc.

The zebrafish has been proposed for the study of the effects of ethanol on the vertebrate brain. Behavioural tests have been successfully employed in the phenotypical characterization of these effects. However, the short scale (minute to minute) time course of ethanol induced changes of zebrafish behaviour has not been analyzed. The current study alleviates this need using a 2×3 chronic×acute ethanol exposure experimental design. We first expose zebrafish to ethanol chronically using a dose escalation procedure in which fish are kept in a final concentration of 0.5% vol/vol ethanol for 10 days while control fish receive identical dosing procedures but no ethanol. Subsequently, we expose zebrafish for 1h to an acute dose of ethanol (0.00, 0.50, or 1.00% vol/vol) and monitor their behaviour throughout this period. We quantify the mean and within-individual temporal variance of distance travelled, distance from bottom and angular velocity using video-tracking, and establish temporal trajectories of ethanol induced behavioural changes in zebrafish. For example, we find fish of the highest acute dose group previously not exposed to chronic ethanol to exhibit an inverted U shaped temporal trajectory in distance travelled (biphasic alcohol effect). We find this response to be blunted after chronic ethanol exposure (development of tolerance). We also describe an acute ethanol withdrawal induced increase in angular velocity. We conclude that temporal analysis of zebrafish behaviour is a sensitive method for the study of chronic and acute ethanol exposure induced functional changes in the vertebrate brain.

BACKGROUND:

Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: (1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and (2) whether cessation of ER tramadol produces opioid withdrawal.

METHODS:

Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved.

RESULTS:

Use of breakthrough withdrawal medication differed significantly (p<0.05) among groups in both phases; the 200mg group received the least amount in Phase 1, and the 600mg group received the most in both phases. In Phase 1, tramadol 200mg produced significantly lower peak ratings than placebo on ratings of insomnia, lacrimation, muscular tension, and sneezing. Only tramadol 600mg produced miosis in Phase 1. In Phase 2, tramadol 600mg produced higher peak ratings of rhinorrhea, irritable, depressed, heavy/sluggish, and hot/cold flashes than placebo. There were no serious adverse events and no signal of abuse liability for tramadol.

CONCLUSIONS:

ER tramadol 200mg modestly attenuated opioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal.

We reviewed stable gastric pentadecapeptide BPC 157-NO-system-relation, its close participation in Moncada's (maintained vascular integrity, platelets control) homeostatic healing response of NO-system to injury. Namely, BPC 157 particular healing effect also affects all events after vascular integrity loss (dependent on circumstances, it reduces either thrombosis (abdominal aorta anastomosis) or bleeding/thrombocytopenia (amputation, heparin, warfarin, aspirin)) and in a series of different injurious models, acute and chronic, BPC 157 consistently advances healing after severe injuries in various tissues spontaneously unable to heal; stimulates egr-1 and naB2 genes; exhibits high safety (LD1 not achieved)). Hypothesis, that BPC 157 (since formed constitutively in the gastric mucosa, stable in human gastric juice, along with significance of NO-synthase and the basal formation of NO in stomach mucosa, greater than that seen in other tissues) exhibits a general, effective competing both with L-arginine analogues (i. e. , L-NAME) and L-arginine, and that this has some physiologic importance (NO-generation), later, practically supports its beneficial effects illustrating BPC 157 and NO-system mutual (with L-NAME/L-arginine; alone and together) relations in (i) gastric mucosa and mucosal protection, following alcohol lesions, in cytoprotection course, NO-generation, and blood pressure regulation; (ii) alcohol acute/chronic intoxication, and withdrawal; (iii) cardiovascular disturbances, chronic heart failure, pulmonary hypertension, and arrhythmias; (iv) disturbances after hypokalemia and hyperkalemia, and potassium-cell membrane dysfunction; and finally, in (v) complex healing failure, proved by the fistulas healing, colocutaneous and esophagocutaneous. However, how this advantage of modulating NO-system (i. e. , particular effect on eNOS gene), may be practically translated into an enhanced clinical performance remains to be determined.

Alcohol addiction is a disease that includes a diverse set of phenotypes. Functional alcohol tolerance is an adaptation to the effects of alcohol that restores neuronal homeostatic balance while the drug is present. When the drug is suddenly withheld, these adaptations unbalance the nervous system and are thought to be the origin of some withdrawal symptoms. Withdrawal symptoms, which can be a motivating factor for alcoholics to relapse, are taken as evidence of physiological ethanol dependence. Both tolerance and withdrawal symptoms are diagnostic criteria for alcoholism. Recent studies have demonstrated that the larvae of Drosophila show conserved alcohol tolerance and withdrawal phenotypes indicating that Drosophila genetics can now be used in studying this endophenotype of alcohol addiction.

BACKGROUND:

European Medicines Agency guidelines recognize two different treatment goals for alcohol dependence: abstinence and reduction in alcohol consumption. All currently approved agents are indicated for abstinence. This systematic review aimed to identify drugs in development for alcohol dependence treatment and to establish, based upon trial design, if any are seeking market authorization for reduction in consumption.

METHODS:

We searched PubMed and Embase (December 2001-November 2011) to identify agents in development for alcohol dependence treatment. Additional studies were identified by searching ClinicalTrials.gov and the R&D Insight and Clinical Trials Insight databases. Studies in which the primary focus was treatment of comorbidity, or n≤20, were excluded. Studies were then classified as 'abstinence' if they: described a detoxification/alcohol withdrawal period; enrolled patients who had undergone detoxification previously; or presented relapse/abstinence rates as the primary outcome. Studies in patients actively drinking at baseline were classified as 'reduction in consumption'.

RESULTS:

Of 602 abstracts identified, 45 full-text articles were eligible. Five monotherapies were in development for alcohol dependence treatment: topiramate, fluvoxamine, aripiprazole, flupenthixol and nalmefene. Nalmefene was the only agent whose sponsor was clearly seeking definitive approval for reduction in consumption. Development status was unclear for topiramate, fluvoxamine, aripiprazole and flupenthixol. Fifteen agents were examined in published exploratory investigator-initiated trials; the majority focused on abstinence. Ongoing (unpublished) trials tended to focus on reduction in consumption.

CONCLUSIONS:

While published studies generally focused on abstinence, ongoing trials focused on reduction in consumption, suggesting a change in emphasis in the approach to treating alcohol dependence.

Single-port laparoscopic colectomy was first described in 2008 as a new technique for colorectal surgery. No available reports have stated the intermediate- or long-term outcome. We report our intermediate results for the first 20 single-port laparoscopic right hemicolectomies performed by a single laparoscopically trained surgeon at our institution.Between February 2009 and September 2010, 20 consecutive patients with an indication for right hemicolectomy who were candidates for laparoscopic surgery underwent a single-port laparoscopic approach. The only exclusion was a previous midline laparotomy. The patients were followed for outcomes after a median of 27 months (range: 15 to 35).The mean age was 65 years (range: 59 to 88). The mean body mass index was 28 (range: 20 to 35). Seventy five percent of patients had significant comorbidities, with an American Society of Anesthesiologists class of III or IV. The median estimated blood loss was 25 mL (range: 25 to 250). The mean number of lymph nodes was 13 (range: 0 to 29). There was one conversion to hand-assisted laparoscopic colectomy and one to open colectomy secondary to bleeding. The mean hospital stay was 5 days (range: 3 to 7). Thirty-day postoperative complications included 1 wound infection, 1 patient with alcohol withdrawal, and 1 incidence of colitis caused by Clostridium difficile infection. At a median follow-up of 27 months, there were no local recurrences or distant metastases. One death occurred at 17 months from myocardial infarction. Two patients developed incisional hernias, with one requiring a laparoscopic hernia repair. One patient required a completion proctocolectomy for a pathological diagnosis of hyperplastic polyposis syndrome.Single-port laparoscopic right hemicolectomy has been safely performed in patients who are candidates for conventional laparoscopic hemicolectomy. This small series indicates that intermediate-term results are similar to conventional laparoscopic surgery in efficacy, safety, and oncological outcomes. Larger datasets are necessary to determine cost-effectiveness, differences in postoperative outcomes, and patient satisfaction.