Impact of a medically supervised safer injecting facility on drug dealing and other drug-related crime

North America's first medically supervised safer injecting facility (SIF) recently opened in Vancouver, Canada. One of the concerns prior to the SIF's opening was that the facility might lead to a migration of drug activity and an increase in drug-related crime. Therefore, we examined crime rates in the neighborhood where the SIF is located in the year before versus the year after the SIF opened. No increases were seen with respect to drug trafficking (124 vs. 116) or assaults/robbery (174 vs. 180), although a decline in vehicle break-ins/vehicle theft was observed (302 vs. 227). The SIF was not associated with increased drug trafficking or crimes commonly linked to drug use.     

HIV seroprevalence among participants at a Supervised Injection Facility in Vancouver, Canada: implications for prevention, care and treatment

North America's first government sanctioned medically supervised injection facility (SIF) was opened during September 2003 in Vancouver, Canada. This was in response to a large open public drug scene, high rates of HIV and hepatitis C transmission, fatal drug overdoses, and poor health outcomes among the city's injection drug users. Between December 2003 and April 2005, a representative sample of 1,035 SIF participants were enrolled in a prospective cohort that required completing an interviewer-administered questionnaire and providing a blood sample for HIV testing. HIV infection was detected in 170/1007 (17%) participants and was associated with Aboriginal ethnicity (adjusted Odds Ratio [aOR], 2.70, 95% Confidence Interval [95% CI], 1.84–3.97), a history of borrowing used needles/syringes (aOR, 2.0, 95% CI, 1.37–2.93), previous incarceration (aOR, 1.87, 95% CI, 1.11–3.14), and daily injection cocaine use (aOR, 1.42, 95% CI, 1.00–2.03). The SIF has attracted a large number of marginalized injection drug users and presents an excellent opportunity to enhance HIV prevention through education, the provision of sterile injecting equipment, and a supervised environment to self-inject. In addition, the SIF is an important point of contact for HIV positive individuals who may not be participating in HIV care and treatment.     

Does routine use of the radial artery increase complexity or morbidity of coronary bypass surgery?

BACKGROUND: Despite increasing data supporting its use, the uptake of radial artery coronary bypass grafting by most surgeons remains low. This may partly be from perceptions that it increases risk or complexity of coronary surgery. METHODS: Data on 151 patients who had radial grafts are compared with 179 concurrent nonrandomized controls that underwent conventional surgery using saphenous vein. Additionally, telephone interviews were conducted on 127 radial recipients to assess subjective outcome. RESULTS: Cardiopulmonary bypass and cross-clamp times were similar in both groups (72 versus 74 minutes and 20 versus 22 minutes). Morbidity was comparable (mortality 1% versus 2%; cerebral vascular accident 1% versus 2%; sternal infection 1% versus 2%; resternotomy 4% versus 6%). Of 127 patients contacted, 41 (32%) reported that they had experienced parasthesia, and 65 (51%) reported numbness related to radial harvest; of these, 75% reported their symptoms as resolved or resolving. Early angiography performed in 36 patients revealed a radial patency rate of 92%. CONCLUSIONS: Concerns about increased morbidity and mortality should not hinder adoption of radial artery grafting.     

Overexpression of connexin 43 in skeletal myoblasts: Relevance to cell transplantation to the heart

OBJECTIVE: Skeletal myoblast transplantation is a promising strategy for treating end-stage heart failure. One potential problem in the development of functional, synchronously contracting grafts is the degree of intercellular communication between grafted myoblasts and host cardiomyocytes. Thus it is expected that enhancement of intercellular gap junction formation would result in improved efficiency of skeletal myoblast transplantation. In this study we investigated whether myoblasts overexpressing connexin 43, a major cardiac gap junction protein, would enhance this intercellular communication. METHODS AND RESULTS: L6 rat skeletal myoblast cell lines overexpressing connexin 43 were generated by means of gene transfection and clonal selection. Connexin 43 overexpression of these myoblasts, which continued both in undifferentiated and differentiated states (up to 17-fold greater protein level in comparison with control-transfected myoblasts, as measured with Western blotting), was observed on cell surfaces where gap junctions should exist. Both dye microinjection and scrape loading with fluorescent dyes showed enhancement in intercellular dye transfer between connexin 43-transfected myoblasts compared with that found in control-transfected cells. Morphologically, these myoblasts fused and differentiated into multinucleated myotubes more rapidly, demonstrating a higher level of cellular creatine kinase activity as a marker of myogenic differentiation throughout the culture period compared with that of control-transfected myoblasts. CONCLUSIONS: We have generated connexin 43-overexpressing skeletal myoblast cell lines that resulted in improved formation of functional intercellular gap junctions, which could be relevant to synchronous contraction of grafted myoblasts in the heart. In addition, these cells demonstrated more rapid differentiation, which would also be advantageous in a graft for transplantation to the heart.     

High prevalence of HIV infection among homeless and street-involved Aboriginal youth in a Canadian setting

Aboriginal people experience a disproportionate burden of HIV infection among the adult population in Canada; however, less is known regarding the prevalence and characteristics of HIV positivity among drug-using and street-involved Aboriginal youth. We examined HIV seroprevalence and risk factors among a cohort of 529 street-involved youth in Vancouver, Canada. At baseline, 15 (2.8%) were HIV positive, of whom 7 (46.7%) were Aboriginal. Aboriginal ethnicity was a significant correlate of HIV infection (odds ratio = 2.87, 95%CI: 1.02 – 8.09). Of the HIV positive participants, 2 (28.6%) Aboriginals and 6 (75.0%) non-Aboriginals reported injection drug use; furthermore, hepatitis C co-infection was significantly less common among Aboriginal participants (p = 0.041). These findings suggest that factors other than injection drug use may promote HIV transmission among street-involved Aboriginal youth, and provide further evidence that culturally appropriate and evidence-based interventions for HIV prevention among Aboriginal young people are urgently required.     

Evidence for endogenous formation of tobacco-specific nitrosamines in rats treated with tobacco alkaloids and sodium nitrite

Carcinogenic tobacco-specific nitrosamines are present in tobacco products and are believed to play a significant role in human cancers associated with tobacco use. Additional amounts of tobacco-specific nitrosamines could be formed endogenously. We tested this hypothesis by treating rats with nicotine and sodium nitrite and analyzing their urine. Initially, we treated groups of rats with (S)-nicotine (60 micromol/kg) and NaNO2 (180 micromol/kg), (S)-nicotine alone, NaNO2 alone or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 12 nmol/kg) by gavage twice daily for 4 days. We collected urine and analyzed for two metabolites of NNK; 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanol and its glucuronide. We did not detect these metabolites in the urine of rats treated with nicotine alone or nicotine plus NaNO2, indicating that endogenous conversion of nicotine to NNK did not occur. However, the urine did contain N'- nitrosonornicotine (NNN), N'-nitrosoanabasine (NAB) and N'- nitrosoanatabine (NAT). Analysis of the (S)-nicotine used in this experiment demonstrated that it contained trace amounts of nornicotine, anabasine and anatabine. In a second experiment, we used an identical protocol to compare the endogenous nitrosation of this (S)-nicotine with that of synthetic (R,S)-nicotine, which did not contain detectable amounts of nornicotine, anabasine or anatabine. NNN (0.53 x 10(-3)% of nicotine dose), NAB (0.68%) and NAT (2.1%) were detected in the urine of the rats treated with the (S)-nicotine and NaNO2. NNN (0.47 x 10(- 3)% of dose), but not NAB or NAT, was present in the urine of the rats treated with synthetic (R,S)-nicotine and NaNO2. NNN probably formed via nitrosation of metabolically formed nornicotine. These results demonstrate for the first time that endogenous formation of tobacco- specific nitrosamines occurs in rats treated with tobacco alkaloids and NaNO2. The potential significance of the results with respect to nitrosamine formation in people who use tobacco products or nicotine replacement therapy is discussed.      

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Is 99Tcm hexamethyl-propyleneamine oxime uptake in the tissues related to glutathione cellular content?

The relationship between the concentration of tissue glutathione (GSH) content and uptake of 99Tcm HMPAO in Sprague Dawley rats was investigated. The GSH content of rat tissue was depleted with diethyl-maleate (DEM) and the ratio of GSH in control to GSH depleted rat was approximately twice that in the brain, liver, kidney, spleen and lung. The GSH content in all the organs studied except the liver had no statistically significant relationship with the uptake of 99Tcm HMPAO. The apparent increase of radioactivity in the liver was due to longer retention of 99Tcm HMPAO. This longer retention was due to stasis of bile flow as confirmed by subsequent experiments in which cholecystokinin (CCK) was administered to GSH depleted rats and compared to the uptake of GSH depleted rats without injection of CCK.