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A nationwide study of intracellular drug metabolite concentrations in children prescribed 6-mercaptopurine for the treatment of lymphoblastic leukaemia was carried out to assess interpatient variability at a standardised dose. Nine children (2% of the total) had completely undetectable metabolites, indicative of non-compliance. Five were adolescents, but otherwise they had no obvious distinguishing characteristics. Not taking any 6-mercaptopurine at all is uncommon, but the problem cannot be predicted. The total number of children who do not comply cannot be determined from this study, but the nine children described represent only a fraction of these. 相似文献
73.
H E Elphick G A Lancaster A Solis A Majumdar R Gupta R L Smyth 《Archives of disease in childhood》2004,89(11):1059-1063
OBJECTIVE: To investigate the validity and reliability of computerised acoustic analysis in the detection of abnormal respiratory noises in infants. METHODS: Blinded, prospective comparison of acoustic analysis with stethoscope examination. Validity and reliability of acoustic analysis were assessed by calculating the degree of observer agreement using the kappa statistic with 95% confidence intervals (CI). RESULTS: 102 infants under 18 months were recruited. Convergent validity for agreement between stethoscope examination and acoustic analysis was poor for wheeze (kappa = 0.07 (95% CI, -0.13 to 0.26)) and rattles (kappa = 0.11 (-0.05 to 0.27)) and fair for crackles (kappa = 0.36 (0.18 to 0.54)). Both the stethoscope and acoustic analysis distinguished well between sounds (discriminant validity). Agreement between observers for the presence of wheeze was poor for both stethoscope examination and acoustic analysis. Agreement for rattles was moderate for the stethoscope but poor for acoustic analysis. Agreement for crackles was moderate using both techniques. Within-observer reliability for all sounds using acoustic analysis was moderate to good. CONCLUSIONS: The stethoscope is unreliable for assessing respiratory sounds in infants. This has important implications for its use as a diagnostic tool for lung disorders in infants, and confirms that it cannot be used as a gold standard. Because of the unreliability of the stethoscope, the validity of acoustic analysis could not be demonstrated, although it could discriminate between sounds well and showed good within-observer reliability. For acoustic analysis, targeted training and the development of computerised pattern recognition systems may improve reliability so that it can be used in clinical practice. 相似文献
74.
Magang Shou Wei Lu Prasad H Kari Cathie Xiang Yuexia Liang Ping Lu Dan Cui W Bart Emary Kimberly B Michel Jennifer K Adelsberger Janice E Brunner A David Rodrigues 《European journal of pharmaceutical sciences》2005,26(2):151-161
Enterohepatic recirculation (EHR) occurs via biliary excretion and intestinal reabsorption of a drug. Drug recycling through EHR can lead to a change in pharmacokinetic (PK) properties, such as reduced clearance (CL), extended half-life (T(1/2)) and increased plasma exposure (AUC). As a result, EHR may prolong the pharmacological effect of drugs. In the present study, the compound (Cpd A) was found to exhibit EHR in Rhesus monkeys associated with a reduction in CL (from 3.8 to 0.33 Lh(-1), IV; from 2.3 to 0.4 Lh(-1), PO), and an increase in T(1/2) (from 0.9 to 18 h, IV) and in AUC (from 1.5 to 17.4 microg h/mL, IV; from 2.8 to 16.3 microg h/mL, PO), by comparing the PK in the monkeys via the interruption of EHR (bile-duct cannulation) with that in the intact monkeys. A population four-compartment model was constructed based on recirculation loops incorporating all possible inputs (bile secretion, a lag-time model for gall bladder emptying, routes and amounts of a single dose administration) to fully evaluate the EHR of Cpd A. The plasma concentrations versus time profiles predicted from the model had a good fit to the values observed in the subjects and were further simulated with 90% confidence interval to demonstrate its utility. Thus, the model could be applied as a useful tool to evaluate the drugs or compounds that undergo EHR in different species. 相似文献
75.
Justo Lorenzo Bermejo Kari Hemminki 《Cancer epidemiology, biomarkers & prevention》2005,14(7):1738-1740
BACKGROUND: Tobacco smoking is the principal cause of lung cancer. The risk of lung cancer in the offspring of lung cancer patients is about twice higher than the risk in the general population. The present study investigated the contribution of shared smoking habits to the familial clustering of lung cancer. METHODS: We estimated the relative risk of lung cancer attributable to smoking according to the extent to which smokers transmit their smoking habits to the offspring (heritability of smoking), the prevalence of smoking in the general population, and the risk of lung cancer for smokers compared with nonsmokers. FINDINGS: The relative risk of lung cancer for the offspring of lung cancer patients attributable to smoking was 1.19 when published data on smoking practice were modeled (i.e., assuming that the heritability of smoking was 0.5, the smoking prevalence 40%, and the odds ratio of lung cancer for smokers versus nonsmokers was 20). INTERPRETATION: Most familial cases of lung cancer cannot be attributed to shared smoking habits. The example of smoking can be used for other familial cancers, for which no strong environmental risk factors are usually known, to infer the primary role for heritable genes. 相似文献
76.
Familial aggregation and heterogeneity of non-Hodgkin lymphoma in population-based samples. 总被引:4,自引:0,他引:4
Lynn R Goldin Ola Landgren Mary L McMaster Gloria Gridley Kari Hemminki Xinjun Li Lene Mellemkjaer J?rgen H Olsen Martha S Linet 《Cancer epidemiology, biomarkers & prevention》2005,14(10):2402-2406
The importance of genetic factors in the etiology of non-Hodgkin lymphoma (NHL) is suggested by case-control and cohort studies. Most previous studies have been too small to estimate accurately risks of specific categories of lymphoproliferative malignancies in relatives of NHL cases or to quantify the contribution of NHL case characteristics to familial risk. We have overcome sample size limitations and potential recall bias by using large databases from Sweden and Denmark. Diagnoses of lymphoproliferative malignancies were compared in 70,006 first-degree relatives of 26,089 NHL cases (including 7,432 with subtype information) versus 161,352 first-degree relatives of 58,960 matched controls. Relatives of NHL cases were at significantly increased risk for NHL [relative risk (RR), 1.73; 95% confidence interval (95% CI), 1.39-2.15], Hodgkin lymphoma (RR, 1.41; 95% CI, 1.0-1.97), and nonsignificantly for chronic lymphocytic leukemia (CLL; RR, 1.31; 95% CI, 0.93-1.85). No increased risk was found for multiple myeloma among case relatives. Findings with respect to siblings compared with parents and offspring or with respect to age at diagnosis of proband were inconsistent. In both populations, relatives of cases with an aggressive NHL subtype were at substantially increased risk of NHL (combined RR, 3.56; 95% CI, 1.80-7.02). We conclude that NHL has an important familial component, which is shared with Hodgkin lymphoma and CLL. We estimate that the absolute lifetime risk for a first-degree relative of an NHL case to develop NHL is 3.6% (compared with a population risk of 2.1%) and higher if the index case had an aggressive subtype of NHL. 相似文献
77.
Ronald Allen Coss Christopher W. Storck Tiffany C. Wells Kari A. Kulp Miriam Wahl Dennis B. Leeper 《International journal of hyperthermia》2014,30(1):75-78
Purpose: This study tested the ability of lonidamine (LND), a clinically applicable inhibitor of monocarboxylate transporters (MCT), to thermally sensitise human melanoma cells cultured at a tumour-like extracellular pH (pHe) 6.7.Materials and methods: Human melanoma DB-1 cells cultured at pHe 6.7 and pHe 7.3 were exposed to 150?µM LND for 3?h, beginning 1?h prior to heating at 42?°C (2?h). Intracellular pH (pHi) was determined using 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) and whole spectrum analysis. Levels of heat shock proteins (HSPs) were determined by immunoblot analysis. Cell survival was determined by colony formation.Results: Treatment with LND at pHe 6.7 reduced pHi to 6.30?±?0.21, reduced thermal induction of HSPs, and sensitised cells growing at pHe 6.7 to 42?°C. When LND was combined with an acute acidification from pHe 6.7 to pHe 6.5, pHi was reduced to 6.09?±?0.26, and additional sensitisation was observed. LND had negligible effects on cells cultured at pH 7.3.Conclusions: The results show that LND can reduce pHi in human melanoma cells cultured at a tumour-like low pHe so that the 42?°C induction of HSPs are abrogated and the cells are sensitised to thermal therapy. Cells cultured at a normal tissue-like pHe 7.3 were not sensitised to 42?°C by LND. These findings support the strategy that human melanoma cells growing in an acidic environment can be sensitised to thermal therapy in vivo by exposure to an MCT inhibitor such as LND. 相似文献
78.
Patricia Leahy‐Warren PhD MSc BSc Hdip PHN RPHN RM RGN Mary Rose Day DN MA BSc Hdip PHN RPHN RM RGN Kari Glavin PhD M.Sc PHN RN MEANS Edith Roth Gjevjon PhD MSc RN MEANS Anne Kjersti Myhrene Steffenak PhD MSc PHN RN Live S. Nordhagen MSc PHN RN Hilde Egge MSc PHN RN Elizabeth Healy MSc PHN RGN 《Public health nursing (Boston, Mass.)》2018,35(4):307-316
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