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Louise T. Henriksen Jacob Nersting Raheel A. Raja Thomas L. Frandsen Steen Rosthj Henrik Schrder Birgitte K. Albertsen 《British journal of haematology》2014,166(2):213-220
L‐asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Cerebrospinal fluid (CSF) asparagine depletion is considered a marker of asparaginase effect in the central nervous system (CNS) and may play a role in CNS‐directed anti‐leukaemia therapy. The objective of this study was to describe CSF asparagine depletion during 30 weeks of pegylated asparaginase therapy, 1000 iu/m2 i.m. every second week, and to correlate CSF asparagine concentration with serum L‐asparaginase enzyme activity. Danish children (1–17 years) with ALL, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, standard and intermediate risk, were included. CSF samples were obtained throughout L‐asparaginase treatment at every scheduled lumbar puncture. A total of 128 samples from 31 patients were available for analysis. Median CSF asparagine concentration decreased from a pre‐treatment level of 5·3 μmol/l to median levels ≤1·5 μmol/l. However, only 4/31 patients (five samples) had CSF asparagine concentrations below the limit of detection (0·1 μmol/l). In 11 patients, 24 paired same day serum and CSF samples were obtained. A decrease in CSF asparagine corresponded to serum enzyme activities above 50 iu/l. Higher serum enzyme activities were not followed by more extensive depletion. In conclusion, pegylated asparaginase 1000 iu/m2 i.m. every second week effectively reduced CSF asparagine levels. 相似文献
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Raheel A. Raja Kjeld Schmiegelow Birgitte K. Albertsen Kaie Prunsild Bernward Zeller Goda Vaitkeviciene Jonas Abrahamsson Mats Heyman Mervi Taskinen Arja Harila‐Saari Jukka Kanerva Thomas L. Frandsen the Nordic Society of Paediatric Haematology Oncology group 《British journal of haematology》2014,165(1):126-133
L‐asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Treatment is associated with several toxicities, including acute pancreatitis. Clinical course, presentation, re‐exposure to L‐asparginase after pancreatitis and risk of recurrent pancreatitis within an asparaginase‐intensive protocol has been poorly reported. Children (1–17 years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase‐associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO ALL toxicity registry. NOPHO ALL2008 includes eight or 15 doses of intramuscular pegylated L‐asparginase (PEG‐asparaginase) 1000 iu/m2/dose at 2–6 weeks intervals, with a total of 30 weeks of exposure to PEG‐asparaginase (clinicaltrials.gov no: NCT00819351). Of 786 children, 45 were diagnosed with AAP with a cumulative risk of AAP of 5·9%. AAP occurred after a median of five doses (range 1–13), and 11 d (median) from the latest administration of PEG‐Asparaginase. Thirteen patients developed pseudocysts (30%) and 11 patients developed necrosis (25%). One patient died from pancreatitis. Twelve AAP patients were re‐exposed to L‐asparginase, two of whom developed mild AAP once more, after four and six doses respectively. In conclusion, re‐exposure to PEG‐asparaginase in ALL patients with mild AAP seems safe. 相似文献
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Bharathi Raja RAJAGANAPATHY Nirmal JAYABALAN Pradeep TYAGI Jonathan KAUFMAN Michael B. CHANCELLOR 《Lower urinary tract symptoms.》2014,6(1):1-10
Radiation treatment for pelvic malignancies is typically associated with radiation injury to urinary bladder that can ultimately lead to radiation cystitis (RC). The late sequelae of radiation therapy may take many years to develop and include bothersome storage symptoms such as hematuria, which may be life‐threatening in severe cases of hemorrhagic cystitis. Although no definitive treatment is currently available, various interventions are used for radiation and hemorrhagic cystitis including blood transfusion, bladder irrigation, intravesical instillation of substances such as alum, silver nitrate, prostaglandins or formalin, and fulguration of intravesical bleeding sites and surgery options such as supravesical urinary diversions and cystectomy. Effects of non‐surgical treatments for radiation and hemorrhagic cystitis are of modest success and studies are lacking to control the effects caused by RC. When such measures have proven ineffective, use of bladder botulinum toxin injection has been reported. New therapy, such as intravesical immunosuppression with local tacrolimus formulation is being developed for the treatment of radiation hemorrhagic cystitis. 相似文献
85.
Halbach M Krausgrill B Hannes T Wiedey M Peinkofer G Baumgartner S Sahito RG Pfannkuche K Pillekamp F Reppel M Müller-Ehmsen J Hescheler J 《Journal of molecular and cellular cardiology》2012,53(3):401-408
Electrophysiological maturation and integration of transplanted cardiomyocytes are essential to enhance safety and efficiency of cell replacement therapy. Yet, little is known about these important processes. The aim of our study was to perform a detailed analysis of electrophysiological maturation and integration of transplanted cardiomyocytes. Fetal cardiomyocytes expressing enhanced green fluorescent protein were transplanted into cryoinjured mouse hearts. At 6, 9 and 12days after transplantation, viable slices of recipient hearts were prepared and action potentials of transplanted and host cardiomyocytes within the slices were recorded by microelectrodes. In transplanted cells embedded in healthy host myocardium, action potential duration at 50% repolarization (APD50) decreased from 32.2±3.3ms at day 6 to 27.9±2.6ms at day 9 and 19.6±1.6ms at day 12. The latter value matched the APD50 of host cells (20.5±3.2ms, P=0.78). Integration improved in the course of time: 26% of cells at day 6 and 53% at day 12 revealed no conduction blocks up to a stimulation frequency of 10Hz. APD50 was inversely correlated to the quality of electrical integration. In transplanted cells embedded into the cryoinjury, which showed no electrical integration, APD50 was 49.2±4.3ms at day 12. Fetal cardiomyocytes transplanted into healthy myocardium integrate electrically and mature after transplantation, their action potential properties after 12days are comparable to those of host cardiomyocytes. Quality of electrical integration improves over time, but conduction blocks still occur at day 12 after transplantation. The pace of maturation correlates with the quality of electrical integration. Transplanted cells embedded in cryoinjured tissue still possess immature electrophysiological properties after 12days. 相似文献
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