Malignant pelvic paraganglioma: A case report

Pheochromocytomas arising from outside the adrenal glands are called paragangliomas and constitute a rare disease and can occur in the pelvic retroperitoneum. Symptoms of excess catecholamine production, as well as elevated urine vanillylmandelic acid levels and serum and urine norepinephrine levels, are highly diagnostic for paraganglioma. Imaging can be helpful for the diagnostic of these pelvic tumors, differentiating them from other pelvic masses. We hereby present a case of pelvic malignant paraganglioma.     

Botulinum Toxin A for Oral Cavity Cancer Patients: In Microsurgical Patients BTX Injections in Major Salivary Glands Temporarily Reduce Salivary Production and the Risk of Local Complications Related to Saliva Stagnation

In patients suffering from oral cavity cancer surgical treatment is complex because it is necessary to remove carcinoma and lymph node metastasis (through a radical unilateral or bilateral neck dissection) and to reconstruct the affected area by means of free flaps. The saliva stagnation in the post-operative period is a risk factor with regard to local complications. Minor complications related to saliva stagnation (such as tissue maceration and wound dehiscence) could become major complications compromising the surgery or the reconstructive outcome. In fact the formation of oro-cutaneous fistula may cause infection, failure of the free flap, or the patient’s death with carotid blow-out syndrome. Botulinum injections in the major salivary glands, four days before surgery, temporarily reduces salivation during the healing stage and thus could reduce the incidence of saliva-related complications. Forty three patients with oral cancer were treated with botulinum toxin A. The saliva quantitative measurement and the sialoscintigraphy were performed before and after infiltrations of botulinum toxin in the major salivary glands. In all cases there was a considerable, but temporary, reduction of salivary secretion. A lower rate of local complications was observed in the post-operative period. The salivary production returned to normal within two months, with minimal side effects and discomfort for the patients. The temporary inhibition of salivary secretion in the post-operative period could enable a reduction in saliva-related local complications, in the incidence of oro-cutaneous fistulas, and improve the outcome of the surgery as well as the quality of residual life in these patients.     

Protective effect of yacon leaves decoction against early nephropathy in experimental diabetic rats

Nephropathy is the most common cause of morbidity and mortality in diabetic patients. Prevention of this complication has a major relevance. Smallanthus sonchifolius (yacon) leaves have been shown to ameliorate hyperglycemia in streptozotocin-induced diabetic rats. We examined the beneficial effects of yacon leaves decoction on diabetic nephropathy and explored the possible underlying action mechanism.     

Pegylated TRAIL retains anti-leukemic cytotoxicity and exhibits improved signal transduction activity with respect to TRAIL

To improve the pharmacokinetic profile of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) an N-terminal specific pegylation was performed to generate pegylated TRAIL (PEG-TRAIL). In in vitro experiments, we found that although PEG-TRAIL was slightly less efficient than recombinant TRAIL in promoting leukemic cell apoptosis, it showed an improved ability to promote migration of bone-marrow mesenchymal stem cells and to elicit the ERK1/2 intracellular signal transduction pathway. Overall, these data suggest that TRAIL pegylation retains, or even enhances, the biological activities of TRAIL relevant for its therapeutic applications.     

Smoking Cessation Pharmacogenetics: Analysis of Varenicline and Bupropion in Placebo-Controlled Clinical Trials

Despite effective therapies for smoking cessation, most smokers find quitting difficult and most successful quitters relapse. Considerable evidence supports a genetic risk for nicotine dependence; however, less is known about the pharmacogenetics of smoking cessation. In the first pharmacogenetic investigation of the efficacy of varenicline and bupropion, we examined whether genes important in the pharmacodynamics and pharmacokinetics of these drugs and nicotine predict medication efficacy and adverse events. Subjects participated in randomized, double-blind, placebo-controlled smoking cessation clinical trials, comparing varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist, with bupropion, a norepinephrine/dopamine reuptake inhibitor, and placebo. Primary analysis included 1175 smokers of European ancestry, and 785 single nucleotide polymorphisms from 24 genes, representing 254 linkage disequilibrium (LD) bins (genes included nAChR subunits, additional varenicline-specific genes, and genes involved in nicotine or bupropion metabolism). For varenicline, continuous abstinence (weeks 9–12) was associated with multiple nAChR subunit genes (including CHRNB2, CHRNA5, and CHRNA4) (OR=1.76; 95% CI: 1.23–2.52) (p<0.005); for bupropion, abstinence was associated with CYP2B6 (OR=1.78; 95% CI: 1.27–2.50) (p<0.001). Incidence of nausea was associated with several nAChR subunit genes (OR=0.50; 95% CI: 0.36–0.70) (p<0.0001) and time to relapse after quitting was associated with HTR3B (HR=1.97; 95% CI: 1.45–2.68) (p<0.0001). These data provide evidence for multiple genetic loci contributing to smoking cessation and therapeutic response. Different loci are associated with varenicline vs bupropion response, suggesting that additional research may identify clinically useful markers to guide treatment decisions.     

Ranolazine for the treatment of refractory angina in a veterans population

BackgroundPivotal ranolazine trials did not require optimization of conventional medical therapy including coronary revascularization and antianginal drug therapy prior to ranolazine use. This case series describes the use of ranolazine for the treatment of chronic stable angina refractory to maximal medical treatment in a veterans population.ResultsA total of 18 patients with a median age of 66 years were identified. All patients had prior percutaneous coronary intervention and/or coronary artery bypass graft surgery; 83% had three-vessel coronary artery disease, with left main disease present in 39% of patients. Prior to initiating ranolazine, antianginal use consisted of beta blockers (94%), long-acting nitrates (83%) and calcium channel blockers (61%). Median blood pressure (116.2/61.8 mmHg) and pulse (65 beats per min) were controlled. Median preranolazine angina episodes and sublingual nitroglycerin (SLNTG) doses per week were 14 and 10, respectively, with a Canadian Cardiovascular Society (CCS) angina grade of III–IV in 67% of patients. After initiation of ranolazine, median angina episodes per week and SLNTG doses used per week decreased to 0.7 and 0, respectively, with CCS grade of III–IV declining to 17%. Of the 18 subjects enrolled, 44% had complete resolution of angina episodes.ConclusionThe addition of ranolazine to maximally tolerated conventional antianginal drug therapy post coronary revascularization was associated with decreases in angina episodes and SLNTG utilization and improvement in CCS angina grades. Ranolazine may provide an effective treatment option for revascularized patients with refractory angina.     

Posttraumatic Stress Disorder and One‐Year Outcome in Methadone Maintenance Treatment

Background: Although opiate use may be associated with posttraumatic stress disorder (PTSD), it is not clear whether PTSD is associated with retention in methadone maintenance. Objectives: To evaluate among those receiving methadone maintenance at an urban methadone maintenance clinic the frequency of life‐time traumatic experiences, the predictors and prevalence of current PTSD, and whether PTSD affects retention at 1 year. Methods: Eighty‐nine people participated in the study. The Post Traumatic Diagnostic Scale was used to determine the prevalence of PTSD. The Life Stressor Checklist Revised was used to evaluate trauma history. Logistic regression analyses examined associations between demographic characteristics, substance use, trauma‐related variables, and PTSD. Similar logistic regression analyses were used to examine retention in methadone maintenance at 1 year. Results: The mean number of reported lifetime stressful events was 8.0 (SD = 3.7). Twenty‐seven percent were diagnosed with PTSD. Nearly 92% of those with PTSD had co‐occurring depressive symptoms. Female gender (adjusted odds ratio [AOR][95% CI]; 3.89 [1.07–14.01]), number of traumatic events (AOR [95% CI]; 1.34 [1.13–1.61]), and less education (AOR [95% CI]; 4.13 [1.14–14.98]) were significantly associated with PTSD. Those with a toxicology positive screen were 80% less likely to remaine in methadone maintenance at 1 year (OR [95% CI]; 0.20 [0.07–0.52]). PTSD diagnosis was not significantly associated with treatment retention at 1 year (OR [95% CI]; 0.61 [0.23–1.64]). Conclusions and Scientific Significance: Future studies are needed to determine if treatment of PTSD that is integrated into methadone maintenance programs may impact continued substance abuse use and thereby improve retention in care. (Am J Addict 2012;21:524–530)