To evaluate if dissolution of asparaginase in lidocaine can relieve pain of an intramuscular injection in children without changes in bioavailability.
The study was designed as a double-blinded study, randomizing 12 children with acute lymphoblastic leukemia (ALL) to four different combinations of injections, including two injections where asparaginase was dissolved in a lidocaine solution and two in sterile water. Seventeen treatment courses of asparaginase, each consisting of four injections, were evaluated. Pain intensity (Pain Visual Analog Scale, VAS-score) and pharmacokinetics of the drug was evaluated.
The pain scores showed a significant difference between the two solutions of asparaginase (+/-lidocaine) (P value < 0.0001). Lidocaine did not influence the pharmacokinetics of the drug.
Asparaginase with addition of lidocaine significantly decreases the pain as measured by the visual analog scale without changing the bioavailability or the absorption rate of the enzyme.
[Show abstract][Hide abstract] ABSTRACT: Treatment decisions are difficult in clinically localised prostate cancer and further biomarkers of aggressive behaviour are required. We investigated the hypothesis that the tissue expression of three cell cycle markers, Rb, p21 and p16, would provide helpful prognostic information in a well characterised series of prostate cancers which were clinically localised and treated conservatively.
The immunohistochemical staining expression of these markers was assessed in tissue microarrays and correlated with 10 year prostate cancer survival and overall survival and then compared with pathological data including contemporary Gleason score, age, measures of tumour extent and initial serum prostate specific antigen (PSA) level.
Rb overexpression did not show any significant association with Gleason score or prostate cancer survival. p21 protein expression showed a significant association with prostate cancer survival (p = 0.02) and overall survival (p = 0.01) in a univariate model but not in a multivariate model with pathological and serum PSA data. There was a significant association between p16 cytoplasmic expression and prostate cancer survival (HR = 2.52, 95%CI = 1.79-3.55, p < 0.001) and overall survival (HR = 1.54, 95% CI = 1.20-1.98, p = 0.001) in a univariate model. p16 expression remained an independent prognostic factor for prostate cancer survival (HR = 1.50, 95%CI = 1.05-2.14, p = 0.03).
We conclude that p16 cytoplasmic expression can be used as a predictor of outcome in conservatively treated prostate cancer. Rb and p21 show no independent association with outcome and therefore further research is not warranted.
[Show abstract][Hide abstract] ABSTRACT: l-asparaginase has been an element in the treatment for acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma since the late 1960s and remains an essential component of their combination chemotherapy. Among the major toxicities associated with l-asparaginase therapy are pancreatitis, allergic reactions, thrombotic events, hepatotoxicity and hyperlipidaemia. Acute pancreatitis is one of the most common reasons for stopping treatment with l-asparaginase. Short-term complications of asparaginase-associated pancreatitis include development of pseudocysts and pancreatic necrosis. Long-term complications include chronic pancreatitis and diabetes. The pathophysiology of asparaginase-associated pancreatitis remains to be uncovered. Individual clinical and genetic risk factors have been identified, but they are only weak predictors of pancreatitis. This review explores the definition, possible risk factors, treatment and complications of asparaginase-associated pancreatitis.
British Journal of Haematology 08/2012; 159(1):18-27. DOI:10.1111/bjh.12016 · 4.71 Impact Factor
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