Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial).

AIMS: Experimental studies have demonstrated that bone marrow (BM) cells can induce angiogenesis in ischaemic myocardium. Recently, several non-randomized pilot studies have also suggested that direct BM cells implantation appears to be feasible and safe in patients with severe coronary artery diseases (CAD). METHODS AND RESULTS: We performed a randomized, blinded, and placebo-controlled trial in 28 CAD patients. After BM harvesting, we assigned patients to receive low dose (1 x 10(6) cells/0.1 mL, n = 9), high dose (2 x 10(6) cells/0.1 mL, n = 10) autologous BM cells or control (0.1 mL autologous plasma/injection, n = 9) catheter-based direct endomyocardial injection as guided by electromechanical mapping. Our primary endpoint was the increase in exercise treadmill time and our secondary endpoints were changes in Canadian Cardiovascular Society (CCS) and New York Heart Association (NYHA) class, and myocardial perfusion and left ventricular ejection fraction (LVEF) assessed by single-photon emission computed tomography and magnetic resonance imaging, respectively. A total 422 injections (mean 14.6 +/- 0.7 per patient) were successfully performed at 41 targeted ischaemic regions without any acute complication. Baseline exercise treadmill time was 439 +/- 182 s in controls and 393 +/- 136 s in BM-treated patients, and changed after 6 months to 383 +/- 223s and 464 +/- 196 s [BM treatment effect +0.43 log seconds (+53%), 95% CI 0.11-0.74, P = 0.014]. Compared with placebo injection, BM implantation was associated with a significant increase in LVEF (BM treatment effect +5.4%, 95% CI 0.4-10.3, P = 0.044) and a lower NYHA class (odds ratio for treatment effect 0.12, 95% CI 0.02-0.73, P = 0.021) after 6 months, but CCS reduced similarly in both groups. We observed no acute or long-term complications, including ventricular arrhythmia, myocardial damage, or development of intramyocardial tumour or calcification associated with BM implantation. CONCLUSION: Direct endomyocardial implantation of autologous BM cells significantly improved exercise time, LVEF, and NYHA functional class in patients with severe CAD who failed conventional therapy.     

Effectiveness of needle and syringe programmes for preventing HIV transmission

Objective: To examine the effectiveness of needle and syringe programmes (NSPs) in preventing HIV transmission among injecting drug users (IDUs).Methods: An ecological study design was used to determine change in HIV prevalence among injecting drug users between cities with and without NSPs. Several data sources, such as electronic journal databases, surveillance reports, websites, and index review of relevant journals, were used to identify studies of HIV seroprevalence among IDUs, and presence of NSPs. The rate of change in HIV prevalence was estimated by regression analysis.Results: There were 778 years of data from 99 cities globally included in the analysis. HIV prevalence decreased by 18.6% per annum in cities that introduce NSPs, and increased by 8.1% in cities that had never introduced NSPs (mean difference −24.7% [95% CI: −43.8, 0.5%], P=0.06). The mean difference was –33% when comparison was weighted to one over the variance of the regression estimator (29% decrease in cities with NSPs and 5% increase in cities without NSPs, P<0.001). When analysis was restricted to cities with first HIV seroprevalence less than 10%, the average annual change in seroprevalence was 18% lower in cities with NSPs (P=0.03).Conclusions: Despite the inherent limitations within an ecological study design, the study provides additional evidence that NSPs reduce transmission of HIV infection. The rapid spread of HIV among IDU populations and increasing rates of injecting in many countries calls for scaling up of NSPs as well as other harm reduction strategies.     

Lymphedema: How Do We Diagnose and Reduce the Risk of This Dreaded Complication of Breast Cancer Treatment?

Lymphedema is an under-recognized, progressive, life-long condition estimated to impact 2-3 million people in the United States. The incidence of breast cancer related lymphedema varies greatly in the literature largely due to different measurement techniques, competing thresholds for defining lymphedema, and variation in length of follow-up. Multiple imaging techniques have become useful for diagnosis. Lymphoscintigraphy is one of the most commonly used, as it can identify pathways of lymphatic drainage, quantify extent of dermal backflow, and help determine functional and morphologic changes in the lymphatic system. Early detection and intervention hold the greatest promise of reducing the incidence of lymphedema. Health care providers involved with cancer patients need to become more educated about lymphedema, aware of current risk-reduction practices, and familiar with methods of diagnosis and assessment, so that patients with early swelling can be referred to lymphedema treatment specialists at a time when treatment is more effective.     

Adding Bupivacaine to High-potassium Cardioplegia Improves Function and Reduces Cellular Damage of Rat Isolated Hearts after Prolonged, Cold Storage

Background: Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone.

Methods: After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 [mu]m bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4[degrees]C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured.

Results: All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline.     

Temporal concordance of anxiety disorders and child sexual abuse: implications for direct versus artifactual effects of sexual abuse.

This study examined the temporal concordance between the onset of childhood anxiety disorders and the points of onset and ending of child sexual abuse (CSA). Sexually abused children (N = 158) were assessed with structured diagnostic interviews. Onset ages for lifetime prevalence anxiety disorders were combined and sequenced with the onset and ending of sexual abuse. Hazard rates were calculated. Departures from the overall linear hazard trajectory for onsets were modeled using piecewise growth curve analyses. Increases from the overall trajectory were found around the point of sexual abuse onset for most childhood anxiety disorders. Decreases were found around the ending of sexual abuse. The risk for developing new anxiety disorders after the onset of sexual abuse showed a positive dose-effect relation with abuse severity. The findings add support to the idea that CSA can have a direct link to childhood anxiety disorders, apart from confounded vulnerability factors, postabuse events, or stable family background factors. The findings are contrasted with those from cross-sectional partial correlation studies that have suggested that there is little direct connection between sexual abuse and mental health outcomes.