Total but not resting energy expenditure is increased in infants with ventricular septal defects

OBJECTIVE: The purpose of this study was to determine the effect of left-to-right shunting on the resting energy expenditure (REE), total energy expenditure (TEE), and energy intake in a group of 3- to 5-month-old infants with moderate to large unrepaired ventricular septal defects (VSDs) compared with age-matched, healthy infants. METHODS: Eight infants with VSDs and 10 healthy controls between 3 to 5 months of age participated in the study. Indirect calorimetry was used to measure REE and the doubly-labeled water method was used to measure TEE and energy intake. An echocardiogram and anthropometric measurements were performed on all study participants. Daily urine samples were collected at home for 7 days. Samples were analyzed by isotope ratio mass spectrometry. Data were compared using analysis of variance. RESULTS: No significant differences were found in REE (VSD, 42.2 +/- 8.7 kcal/kg/d; control, 43.9 +/- 14.1 kcal/kg/d) or energy intake (VSD, 90.8 +/- 19.9 kcal/kg/d; control, 87.1 +/- 11.7 kcal/kg/d) between the groups. The percent total body water was significantly higher in the VSD infants and the percent fat mass was significantly lower. TEE was 40% higher in the VSD group (VSD, 87.6 +/- 10.8 kcal/kg/d; control, 61.9 +/- 10.3 kcal/kg/d). The difference between TEE and REE, reflecting the energy of activity, was 2.5 times greater in the VSD group. CONCLUSIONS: REE and energy intake are virtually identical between the two groups. Despite this, infants with VSDs have substantially higher TEE than age-matched healthy infants. The large difference between TEE and REE in VSD infants suggests a substantially elevated energy cost of physical activity in these infants. These results demonstrate that, although infants with VSDs may match the energy intake of healthy infants, they are unable to meet their increased energy demands, resulting in growth retardation.     

Asparagine synthetase activity in paediatric acute leukaemias: AML-M5 subtype shows lowest activity

Lack of sufficient cellular activity of asparagine synthetase (AS) in blast cells compared with normal tissue is thought to be the basis of the antileukaemic effect of L-asparaginase in acute lymphoblastic leukaemia (ALL). Although L-asparaginase is routinely used in ALL, its role and value in the treatment of acute myelogenous leukaemia (AML) is still being discussed. To evaluate the pharmacological basis for L-asparaginase treatment, we established pretreatment monitoring of the intracellular AS activity in blast cells of patients with AML and ALL. There was no general difference in AS activity between ALL and AML samples. Significantly lower AS activity, however, was found in the B-lineage ALL subgroups as well as AML-M5.     

Pegylated asparaginase in combination with high-dose methotrexate for consolidation in adult acute lymphoblastic leukaemia in first remission: a pilot study

The German Multicentre acute lymphoblastic leukaemia (ALL) study group (GMALL) performed a pilot study using pegylated asparaginase (PEG-ASP) in combination with high-dose methotrexate as consolidation therapy in the 05/93 protocol. The aim of the study was an intra-individual comparison of two different doses of PEG-ASP in 26 patients, with regard to the depletion of asparagine in serum and toxicity. 'Pharmacokinetic' monitoring was performed to evaluate the effect of an intra-individual dose escalation of PEG-ASP from 500 to 1000 U/m2 intravenously in successive doses. Serum asparaginase activity was targeted at > or =100 U/l for 1 week and > or =50 U/l for 10 d. The second course of PEG-ASP was administered to 23 patients. Due to hypersensitivity reactions in five patients, only 18 patients were evaluable for pharmacokinetic monitoring. With respect to the PEG-ASP activity, an effective depletion of asparagine could be postulated in the majority of patients during 10 d after the first administration. The effect of an intraindividual dose escalation form 500 to 1000 U/m2 was evaluable in 17 of 22 patients. An increment in peak PEG-ASP activity >70% was observed in 65% of the patients. PEG-ASP was well tolerated. Despite the long half-life of PEG-ASP, neither pancreatic nor central nervous toxicities occurred among the 26 adult patients treated in this pilot study.     

清开灵与利巴韦林治疗小儿呼吸道合胞病毒肺炎的比较：单盲、随机、平行对照试验

目的:比较清开灵与利巴韦林对呼吸道合胞病毒肺炎患儿治疗效果的差异。方法:选择2005-02/2006-04在北京儿童医院分中心治疗的小儿呼吸道合胞病毒肺炎97例,患儿法定监护人知情同意。采用单盲、随机、平行对照试验的原则,按区组随机化方法分为2组,清开灵注射液组49例,利巴韦林组48例。①清开灵注射液组:清开灵注射液静脉滴注加口服中成药。②利巴韦林组:利巴韦林注射液静脉滴注加口服复方愈创木酚磺酸钾口服液。两组疗程均为10d,比较两组患儿的疗效。结果:清开灵注射液组脱落3例,利巴韦林组脱落1例,进入结果分析清开灵注射液组46例,利巴韦林组47例。①清开灵注射液组发热患儿体温恢复正常时间比利巴韦林组短[(2.72±1.86)d,(6.29±2.41)d(P<0.01)]。②清开灵注射液组患儿咳嗽、痰壅、气促症状积分改善方面优于利巴韦林组(P<0.05～0.01)。③清开灵注射液组的呼吸道合胞病毒转阴时间明显优于利巴韦林组。④咳嗽、痰壅、病毒转阴时间、气促均进入Logistic模型,其中前两个症状的回归系数绝对值较大。结论:清开灵注射液治疗小儿呼吸道合胞病毒肺炎在退热、止咳平喘、呼吸道合胞病毒转阴时间等方面均具有明显优势,咳嗽、痰壅这两个症状更能反映清开灵注射液的疗效优于利巴韦林。     

人表皮细胞与角膜上皮细胞蛋白质组的差异表达初步研究

目的：应用蛋白质组技术比较人表皮细胞与角膜上皮细胞之间的蛋白质表达差异。方法：实验于2005-11，2006-10在中山大学中山眼科中心国家眼科学重点实验室完成。分别培养人表皮细胞与角膜上皮细胞，裂解原代细胞抽提总蛋白，精确定量后进行双向电泳，扫描电泳凝胶获得二维总蛋白图谱。图谱使用软件辅助比较分析，找出差异表达点，从凝胶中抠取差异点，胶内酶解后用基质辅助激光解吸附，电离飞行时间串级质谱法鉴定差异蛋白。结果：人表皮细胞与角膜上皮细胞蛋白质凝胶分析获得600余个清晰的蛋白质斑点，在比较分析出的26个差异点中初步鉴定出4个差异表达蛋白，分别是细胞内氯离子通道1、Psodasin、乳酸脱氢酶B和丝氨酸蛋白酶抑制因子。结论：人表皮细胞与角膜上皮细胞在蛋白质表达上有较高的相似性以及较好的可比性，为探索表皮细胞横向分化成角膜上皮细胞的分子机制做出了有益的尝试，并提供了具有一定可操作性的实验方法。     

A population pharmacokinetic model for pegylated-asparaginase in children

We analysed 1221 serum activity measurements in 168 children from the Berlin-Frankfürt-Münster acute lymphoblastic leukaemia studies, ALL-BFM (Berlin-Frankfürt-Münster) 95 and ALL-BFM REZ, in order to develop a pharmacokinetic model describing the activity-time course of pegylated (PEG)-asparaginase for all dose levels. Patients received 500, 750, 1000 or 2500 U/m² PEG-asparaginase on up to nine occasions. Serum samples were analysed for asparaginase activity and data analysis was done using nonlinear mixed effects modelling (NONMEM Vers. VI, Globomax, Hanouet, MD, USA). Different linear and nonlinear models were tested. The best model applicable to all dosing groups was a one-compartmental model with clearance (Cl) increasing with time according to the formula: Cl=Cl_i * e ^{(0·0793 * t )} where Cl_i = initial clearance and t  = time after dose. The parameters found were: volume of distribution ( V ) 1·02 ± 26% l/m², Cl_i 59·9 ± 59% ml/d per m² (mean ± interindividual variability). Interoccasion variability was substantial with 0·183 l/m² for V and 44·7 ml/d per m² for Cl, respectively. A subgroup of the patients showed a high clearance, probably due to the development of inactivating antibodies. This is the first model able to predict the activity-time course of PEG-asparaginase at different dosing levels and can therefore be used for developing new dosing regimens.     

The effects of coronary artery disease severity on time-dependent changes in platelet activation indices in stored whole blood

Background Platelets play a pivotal role in the pathogenesis of the thrombotic complications in cardiovascular disease (CVD). Abnormal platelet activation indices are evolving as potentially useful markers in CVD risk stratification. Whilst there has been some investigation into the effects of storage time on several of these indices, the effects of underlying disease severity on these temporal changes have not been previously studied. Methods Using the ADVIA^TM120 haematology analyser, we assessed the effects of time-dependent storage of whole blood in EDTA, on a number of platelet activation indices: mean platelet volume (MPV), mean platelet component (MPC, measure of platelet density) and platelet component distribution width (PCDW, a marker of platelet shape change. We studied three age- and sex-matched patient groups: (i) healthy controls (n = 10), (ii) stable patients with coronary artery disease (CAD, n = 9); and (iii) patients with acute myocardial infarction (n = 8). Whole blood samples were processed at exactly 5 min following venesection and at 15, 30, 60 and 120 min later in storage in EDTA tubes at room temperature. Results There was a significant and stepwise increase in MPV (P = 0.01) and decrease in PCDW (P = 0.03), with a non-significant trend to increasing MPM and decreasing MPC with increasing underlying disease (that is healthy, ‘stable’ and ‘acute’ artery disease). There was a significant time-dependent increase in MPV and decrease in MPC and PCDW (all P < 0.05), which were all significant on ‘post-hoc’ analyses by 30 min. There were no significant changes in platelet count or MPM with time. There was no interaction of underlying disease with whole-blood storage time for any of the platelet indices reported (P = NS). Conclusion There is a temporal increase in MPV and decrease in MPC and PCDW in venous blood stored over 2 h in EDTA. These changes are not influenced by the underlying CVD disease severity.     

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.