Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition.

Evidence shows that the endocannabinoid system modulates the addictive properties of nicotine. In the present study, we hypothesized that spontaneous withdrawal resulting from removal of chronically implanted transdermal nicotine patches is regulated by the endocannabinoid system. A 7-day nicotine dependence procedure (5.2 mg/rat/day) elicited occurrence of reliable nicotine abstinence symptoms in Wistar rats. Somatic and affective withdrawal signs were observed at 16 and 34 hours following removal of nicotine patches, respectively. Further behavioral manifestations including decrease in locomotor activity and increased weight gain also occurred during withdrawal. Expression of spontaneous nicotine withdrawal was accompanied by fluctuation in levels of the endocannabinoid anandamide (AEA) in several brain structures including the amygdala, the hippocampus, the hypothalamus and the prefrontal cortex. Conversely, levels of 2-arachidonoyl-sn-glycerol were not significantly altered. Pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the intracellular degradation of AEA, by URB597 (0.1 and 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety as assessed by the elevated plus maze test and the shock-probe defensive burying paradigm, but did not prevent the occurrence of somatic signs. Together, the results indicate that pharmacological strategies aimed at enhancing endocannabinoid signaling may offer therapeutic advantages to treat the negative affective state produced by nicotine withdrawal, which is critical for the maintenance of tobacco use.

Prevention of the renarrowing of coronary arteries using drug-eluting stents in the perioperative period: an update.

The management of patients scheduled for surgery with a coronary stent, and receiving 1 or more antiplatelet drugs, has many controversies. The premature discontinuation of antiplatelet drugs substantially increases the risk of stent thrombosis (ST), myocardial infarction, and cardiac death, and surgery under an altered platelet function could also lead to an increased risk of bleeding in the perioperative period. Because of the conflict in the recommendations, this article reviews the current antiplatelet protocols after positioning a coronary stent, the evidence of increased risk of ST associated with the withdrawal of antiplatelet drugs and increased bleeding risk associated with its maintenance, the different perioperative antiplatelet protocols when patients are scheduled for surgery or need an urgent operation, and the therapeutic options if excessive bleeding occurs.

Transcatheter aortic valve replacement for degenerative bioprosthetic surgical valves: Results from the global valve-in-valve registry.

BACKGROUND Transcatheter aortic valve-in-valve implantation is an emerging therapeutic alternative for patients with a failed surgical bioprosthesis and may obviate the need for reoperation. We evaluated the clinical results of this technique using a large, worldwide registry. METHODS AND RESULTS The Global Valve-in-Valve Registry included 202 patients with degenerated bioprosthetic valves (aged 77.7±10.4 years; 52.5% men) from 38 cardiac centers. Bioprosthesis mode of failure was stenosis (n=85; 42%), regurgitation (n=68; 34%), or combined stenosis and regurgitation (n=49; 24%). Implanted devices included CoreValve (n=124) and Edwards SAPIEN (n=78). Procedural success was achieved in 93.1% of cases. Adverse procedural outcomes included initial device malposition in 15.3% of cases and ostial coronary obstruction in 3.5%. After the procedure, valve maximum/mean gradients were 28.4±14.1/15.9±8.6 mm Hg, and 95% of patients had ≤+1 degree of aortic regurgitation. At 30-day follow-up, all-cause mortality was 8.4%, and 84.1% of patients were at New York Heart Association functional class I/II. One-year follow-up was obtained in 87 patients, with 85.8% survival of treated patients. CONCLUSIONS The valve-in-valve procedure is clinically effective in the vast majority of patients with degenerated bioprosthetic valves. Safety and efficacy concerns include device malposition, ostial coronary obstruction, and high gradients after the procedure.

Role of the paclitaxel-eluting stent and tirofiban in patients with ST-elevation myocardial infarction undergoing postfibrinolysis angioplasty: the GRACIA-3 randomized clinical trial.

BACKGROUND A catheter-based approach after fibrinolysis is recommended if fibrinolysis is likely to be successful in patients with acute ST-elevation myocardial infarction. We designed a 2x2 randomized, open-label, multicenter trial to evaluate the efficacy and safety of the paclitaxel-eluting stent and tirofiban administered after fibrinolysis but before catheterization to optimize the results of this reperfusion strategy. METHODS AND RESULTS We randomly assigned 436 patients with acute ST-elevation myocardial infarction to (1) bare-metal stent without tirofiban, (2) bare-metal stent with tirofiban, (3) paclitaxel-eluting stent without tirofiban, and (4) paclitaxel-eluting stent with tirofiban. All patients were initially treated with tenecteplase and enoxaparin. Tirofiban was started 120 minutes after tenecteplase in those patients randomly assigned to tirofiban. Cardiac catheterization was performed within the first 3 to 12 hours after inclusion, and stenting (randomized paclitaxel or bare stent) was applied to the culprit artery. The primary objectives were the rate of in-segment binary restenosis of paclitaxel-eluting stent compared with that of bare-metal stent and the effect of tirofiban on epicardial and myocardial flow before and after mechanical revascularization. At 12 months, in-segment binary restenosis was similar between paclitaxel-eluting stent and bare-metal stent (10.1% versus 11.3%; relative risk, 1.06; 95% confidence interval, 0.74 to 1.52; P=0.89). However, late lumen loss (0.04+/-0.055 mm versus 0.27+/-0.057 mm, P=0.003) was reduced in the paclitaxel-eluting stent group. No evidence was found of any association between the use of tirofiban and any improvement in the epicardial and myocardial perfusion. Major bleeding was observed in 6.1% of patients receiving tirofiban and in 2.7% of patients not receiving it (relative risk, 2.22; 95% confidence interval, 0.86 to 5.73; P=0.14). CONCLUSIONS This trial does not provide evidence to support the use of tirofiban after fibrinolysis to improve epicardial and myocardial perfusion. Compared with bare-metal stent, paclitaxel-eluting stent significantly reduced late loss but appeared not to reduce in-segment binary restenosis. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov. Unique identifier: NCT00306228.

Fracturas femorales periprotésicas de rodilla tratadas con clavo intramedular retrógrado y osteosíntesis con placa: comparación de resultados a medio-largo plazo

INTRODUCTION: The femoral periprosthetic fracture of the knee is one of the most feared complications because of its repercussions. Incidence are more and more likely due to the increase of total implanted arthroplasty of the knee, due to the increasing lifespan among the general population. The objective of this study is to analyze some of the perioperative aspects of the treatment of these fractures, comparing the use of osteosynthesis with plates and the retrograde nailing in those patients with femoral periprosthetic knee fractures with a stable implant. MATERIAL AND METODS: The study retrospectively examines 18 cases treated consecutively in our hospital (3 men and 15 women, average age of 72.7 years) between the years of 2000 and 2009. All fractures were located in the distal femur and on a stable implant. Eight were treated through retrograde nailing (Group I) and ten with plates (Group II). The cases are analyzed through the tests of the University of Mann-Withney and the exact Fischer test, with significant values of p≤0.05, the variables of median hospital stay, necessity of transfusion indicated with values of hemoglobin less than 8 mg/ml, preoperative radiological alignment and postoperative alignment of the total knee prosthesis (TKR), measured following the anatomical tibiofemoral axis, time of consolidation and incidence of localized complications in both groups. RESULTS: We did not find any statistically significant differences between the two groups in any of the variables analyzed. Localized complications are more frequent in Group I (62.5 percent of patients) than in Group II (10 percent of patients). The need for transfusion is greater in Group II (40 percent) than in Group I (12.5 percent). CONCLUSIONS: The type of implant used in treatment of femoral periprosthetic knee fracture does not significantly influence perioperative factors. The treatment for this type of fractures should be individually chosen in relation to the type of fracture, characteristics of the patient and stability and prosthesis model of the primary knee.

Prótesis unicompartimental como opción quirúrgica en la gonartrosis medial en el adulto joven

OBJECTIVE: Assess the degree of satisfaction in a series of patients between 50 and 60 years of age who underwent surgery in our unicompartmental prosthesis unit (UPU) for monocompartmental gonarthrosis. Likewise, the definition based on current literature is assessed, as well as our experience in the indications, inconveniences and results of the internal knee unicompartmental arthroplasty discussed with supra-tuberosity tibial osteotomy, which was the common surgical option in these cases.MATERIAL AND METHOD: This study included 19 patients between 50 and 60 years of age (average age 56.7 years) (Interval of 51-60 years) intervened between 7/2007 and 11/2011 by the same surgeon (GDFB). Functional assessment used the Oxford Knee Score (OKS) questionnaire. A bibliographic search was performed in the MEDLINE, COCHRANE and EMBASE databases from 1988 to 2012. RESULTS: With an average follow-up of 29.4 months, 16 of 19 patients stated that they were satisfied with the results obtained and would repeat the intervention. One patient sufered a prosthetic infection and was reviewed for total knee replacement with good results. CONCLUSIONS: the medial, unicompartmental arthroplasty of the knee is a valid surgical option and reproducible in the medium term treatment of monocompartmental gonarthrosis in patients between 50 and 60 years of age.

Recambios en un solo tiempo de prótesis de cadera y rodilla sobre terreno contaminado: nuestra experiencia

Objective: Evaluate the results obtained in the simultaneous replacement of a septic arthroplasty or a second septic replacement (implanting the prosthesis in a contaminated eld). Material and method: Series of 17 cases, with a mean age of 66.8 years and average follow-up of 49 months. The exclusion criteria were serious immunological depression and unknown germ or not sensitive to at least three antibiotics. After the intervention, the corresponding antibiotics were administered between six weeks and three months. Recovery was established as the normality for infection indicator variables at least nine months after the replacement. Results: 14 patients developed towards total recovery (follow-up at least 9 months and maximum 84 months). 3 cases presented relapse, all three carriers of Staphylococcus epidermidis (at 1, 3 and 7 months of follow-up respectively). The success percentage is 82.41% (average follow-up of 49 months). Conclusions: Simultaneous replacements is an interesting option for patients with plural pathologies as it o"ers a single operation, less morbidity, quicker return to activities to restore normal function and less associated costs

Thorax, pelvis and hip pattern in the frontal plane during walking in unilateral transtibial amputees: biomechanical analysis.

BACKGROUND Lower limb amputees exhibit postural control deficits during standing which can affect their walking ability. OBJECTIVES The primary purpose of the present study was to analyze the thorax, pelvis, and hip kinematics and the hip internal moment in the frontal plane during gait in subjects with Unilateral Transtibial Amputation (UTA). METHOD The participants included 25 people with UTA and 25 non-amputees as control subjects. Gait analysis was performed using the Vicon(r) Motion System. We analyzed the motion of the thorax, pelvis, and hip (kinematics) as well as the hip internal moment in the frontal plane. RESULTS The second peak of the hip abductor moment was significantly lower on the prosthetic side than on the sound side (p=.01) and the control side (right: p=.01; left: p=.01). During middle stance, the opposite side of the pelvis was higher on the prosthetic side compared to the control side (right: p=.01: left: p=.01). CONCLUSIONS The joint internal moment at the hip in the frontal plane was lower on the prosthetic side than on the sound side or the control side. Thorax and pelvis kinematics were altered during the stance phase on the prosthetic side, presumably because there are mechanisms which affect postural control during walking.

Prótesis unicompartimental lateral de rodilla. Indicaciones, técnica y resultados a mediocorto plazo

Objectives: In patients with lateral osteoarthritis of the knee, use of external unicompartmental knee arthroplasty it is a well known surgical alternative, used by the minor trauma involved, short hospital stay and rapid recovery. The purpose of this study is to show the clinical outcomes to short-medium term of patients undergoing this procedure. Methods: we describe the technique used and the peculiarities of the prosthesis (A Mobile-bearing lateral unicompartmental knee replacement, Oxford Domed ®). This is an observational retrospective longitudinal study, of 15 arthroplasties performed in 13 women and 2 men, between 2010 and 2013, with a mean age of 60’7 years, with a diagnosis of lateral osteoarthritis of the knee, without involvement of the medial or patellofemoral compartment and cruciate ligaments functionally intact, with a mean follow up of 25 months. All patients complete the Oxford Knee Score and Visual Analog Scale (VAS) during the study. Results: The results are favorable, with an improvement of 6.60 points on the EVA, 3.73 for 1 in the postoperatory funcionality, the OKS very satisfactory with an average of 38 points over 50 and without any postoperative function surgical revision. Anserine tendinitis was observed in 20% of cases. Conclusions: The benefits of this surgery against their alternatives are assessed, and their potential drawbacks. External unicompartmental knee arthroplasty is an effective alternative in cases of knee osteoarthritis of the lateral compartment with no other associated injuries.

Edge vascular response after polymer-free vs. polymer-based paclitaxel-eluting stent implantation.

BACKGROUND It is unknown if lack of polymer can provoke a different edge response in drug-eluting stents. The aim of this study was to compare edge vascular response between polymer-free paclitaxel-eluting stent (PF-PES) and polymer-based paclitaxel-eluting stents (PB-PES). METHODS AND RESULTS: A total of 165 eligible patients undergoing percutaneous coronary intervention were prospectively randomized 1:1 to receive either PF-PES or PB-PES. Those patients with paired intravascular ultrasound (IVUS) after procedure and at 9-month follow-up were included in this analysis.Seventy-six patients with 84 lesions, divided into PB-PES (38 patients, 41 lesions) and PF-PES groups (38 patients, 43 lesions) had paired post-procedure and 9-month follow-up IVUS and were therefore included in this substudy. There was a significant lumen decrease at the proximal edge of PF-PES (from 9.02±3.06 mm(2)to 8.47±3.05 mm(2); P=0.040), and a significant plaque increase at the distal edges of PF-PES (from 4.39±2.73 mm(2)to 4.78±2.63 mm(2); P=0.004). At the distal edge there was a significant plaque increase in the PF-PES compared to PB-PES (+8.0% vs. -0.6%, respectively; P=0.015) with subsequent lumen reduction (-5.2% vs. +6.0%, respectively; P=0.024). CONCLUSIONS PF-PES had significant plaque increase and lumen reduction at the distal edge as compared to PB-PES, probably due to difference in polymer-based drug-release kinetics between the 2 platforms.