Publications by authors named "Helen Dodds"

4 Publications

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Meeting the needs of young people in hospital.

Authors:
Helen Dodds

Paediatr Nurs 2010 Nov;22(9):14-8

Queen's Medical Centre, Nottingham.

A critical review of the literature about the primary needs of young inpatients was conducted following principles delineated by Polit and Hungler (1997). Three were identified: privacy, independence and psychosocial support. The author concludes that adjustments to existing ward facilities are a more viable option than the provision of universally established 'adolescent units'. Success in meeting the challenges is ultimately determined by the nurses providing care on the front line.
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http://dx.doi.org/10.7748/paed2010.11.22.9.14.c8063DOI Listing
November 2010

The relative contributions of carboxylesterase and beta-glucuronidase in the formation of SN-38 in human colorectal tumours.

Oncol Rep 2003 Nov-Dec;10(6):1977-9

Department of Pharmacology, University of Sydney, New South Wales, Australia.

Irinotecan (CPT-11) is a prodrug that is used to treat metastatic colorectal cancer. It is activated to the topoisomerase poison SN-38 by carboxylesterases. SN-38 is subsequently metabolised to its inactive glucuronide, SN-38G, which can however be reactivated to SN-38 by beta-glucuronidase. The purpose of this study was to examine the role of carboxylesterases and beta-glucuronidase in the in vitro production of SN-38 in human colorectal tumours. The production of SN-38 from CPT-11 and SN-38G was measured by HPLC in human colorectal tumour homogenates. Carboxylesterase and beta-glucuronidase activities were found to be lower in tumour tissues compared to matched normal colon mucosa samples. In colorectal tumour, beta-glucuronidase and carboxylesterase-mediated SN-38 production rates were comparable at clinically relevant concentrations of SN-38G and CPT-11, respectively. Therefore, tumour beta-glucuronidase may play a significant role in the exposure of tumours to SN-38 in vivo, particularly during prolonged infusions of CPT-11.
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June 2004

High-performance liquid chromatographic assay with fluorescence detection for the simultaneous measurement of carboxylate and lactone forms of irinotecan and three metabolites in human plasma.

J Chromatogr B Analyt Technol Biomed Life Sci 2003 May;788(1):65-74

Department of Pharmaceutical Sciences, Mail Stop 313, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105-2794, USA.

Irinotecan (CPT-11), a camptothecin analog, is metabolized to SN-38, an active topoisomerase I inhibitor, and inactive metabolites, including APC and SN-38 glucuronide (SN-38G). A high-performance liquid chromatographic assay method to simultaneously measure the lactone and carboxylate forms of CPT-11, SN-38, SN-38G, and APC in human plasma was developed. Chromatography was accomplished with a reversed-phase C(8) column and fluorescence detection. A gradient mobile phase system was used. The buffer for mobile phase A consisted of 0.75 M ammonium acetate, 5 mM tetrabutylammonium phosphate (pH 6.0), and acetonitrile (86:14, v/v). The buffer for mobile phase B was identical to mobile phase A with the exception of the concentration (50:50, v/v). Precipitation of plasma proteins was performed with cold methanol. The linear range of detection of the lactone and carboxylate forms of SN-38, SN-38G, and APC was 2-25 ng/ml, and 5-300 ng/ml for CPT-11. The limit of quantitation for the analytes ranged from 0.5 to 5 ng/ml. Analysis of patients' plasma samples obtained before and after CPT-11 administration showed that the assay is suitable for measuring lactone and carboxylate forms of CPT-11, SN-38, SN-38G, and APC in clinical studies.
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http://dx.doi.org/10.1016/s1570-0232(02)01016-4DOI Listing
May 2003

The importance of tumor glucuronidase in the activation of irinotecan in a mouse xenograft model.

J Pharmacol Exp Ther 2002 Nov;303(2):649-55

Department of Pharmacology, University of Sydney, New South Wales, Australia.

The anticancer drug irinotecan (CPT-11) is activated to the potent topoisomerase I inhibitor, SN-38 (7-ethyl-10-hydroxycamptothecin), by esterases. SN-38 is in turn conjugated to the inactive SN-38 glucuronide (SN-38G). The reverse reaction is mediated by beta-glucuronidases. Hence, production of SN-38 may occur through either pathway. In this study we conducted in vitro studies to examine these two reactions in neuroblastoma xenograft tumors (NB1691) and compared the rates of SN-38 production with those observed in the liver and plasma of the host SCID (severe-combined immunodeficient) mice. The rate of formation of SN-38 from CPT-11 by esterases slowed considerably during a 60-min incubation, consistent with the known deacylation-limited nature of this reaction. For xenograft tumor tissue, K(m) and V(max) values of 1.6 microM and 4.4 pmol/min/mg of protein, respectively, were observed. By comparison, these parameters were estimated to be 6.9 microM and 9.4 pmol/min/mg for mouse liver and 2.1 microM and 40.0 pmol/min/mg for mouse plasma, respectively. The formation of SN-38 from SN-38G was very pronounced in both liver and xenograft tumor tissue, in which it was nonsaturable (0.125-50 microM) and time-independent (0-60 min). The derived values of V(max)/K(m) were 0.65 microl/min/mg for the tumor and 2.12 microl/min/mg for the liver preparations. Microdialysate experiments revealed the concentrations of SN-38G and CPT-11 in tumor to be comparable. At equal substrate concentrations, production of SN-38 from SN-38G in tumor extracts was comparable with that from CPT-11. Therefore, reactivation of SN-38 in the tumor by beta-glucuronidases may represent an important route of tumor drug activation for CPT-11.
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http://dx.doi.org/10.1124/jpet.102.039040DOI Listing
November 2002