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Postprandial response curves of [beta]-carotene and retinyl esters in a triglyceride-rich lipoprotein (TRL) fraction were evaluated as a potential measure of [beta]-carotene uptake and cleavage. [Beta]-Carotene, retinyl ester, and triglyceride concentrations in the TRL fraction (density < 1.006 kg/L) and plasma were measured in 10 men for 8 or 16 h after an oral dose of 15 mg [beta]-carotene. The [beta]-carotene response, unlike the triglyceride and retinyl ester response, can be evaluated in the TRL fraction but not in plasma. Intraindividual variations in the triglyceride-adjusted response of [beta]-carotene and retinyl palmitate in TRL fractions were 23% and 20% and interindividual variations were 42% and 36%, respectively. A low [beta]-carotene response was associated with a high ratio between retinyl palmitate and [beta]-carotene responses (r = -0.56, P = 0.013). In conclusion, the measurement of [beta]-carotene and retinyl esters in the TRL fraction after a dose of [beta]-carotene with a vitamin A-free meal may be an appropriate method to study [beta]-carotene uptake and cleavage.

Children developing an isolated central nervous system (CNS) relapse as first recurrence of their acute lymphoblastic leukemia (ALL) are considered to have a systemic relapse as well. They are mostly treated with intensive chemotherapy and craniospinal irradiation. In most treatment schedules, irradiation is given early after induction treatment. Because craniospinal irradiation affects a large portion of hematopoietic bone marrow systemically, treatment is often delayed owing to aplasias. Also, dose reductions are frequently needed. Children receiving simultaneously irradiation and chemotherapy are prone to (often severe) neurotoxicity. This study reports on children with a first isolated CNS relapse of their ALL receiving chemotherapy for 40 weeks. Treatment ends with the administration of irradiation given after cessation of chemotherapy. Fourteen children, with blasts and >5 cells/mm³ in two consecutive samples of cerebrospinal fluid and a blast per-centage &lt;5% in their bone marrow were treated according to an intensive systemic and site-specific chemotherapy. Craniospinal irradiation was administered after cessation chemotherapy. Event-free-survival was 57% (confidence interval 35–89%), freedom from relapse was 61.5%; follow-up ranges from 2.0 to 15.1 years (median 11.7 years). One child died from septicemia during induction. Five children experienced a second relapse and died from their malignancy. Two children [with a t(9;22) or a rearranged MLL gene] relapsed prior to radiotherapy. Outcome was related to duration of first remission, age at relapse, and identification as a high-risk patient at initial diagnosis. No neurologic complications were noted during and after treatment. Delayed irradiation for isolated CNS relapse in children with ALL gives favorable survival rates, without significant toxicity. Neurotoxicity was absent. Med. Pediatr. Oncol. 34:402–406, 2000. © 2000 Wiley-Liss, Inc.

Bcl-2 over-expression has been shown to inhibit apoptosis induced by a variety of stimuli, whereas a predominance of Baxα to Bcl-2 accelerates apoptosis upon apoptotic stimuli. We sought to study the relevance of these apoptotic regulating gene products in leukaemia. In a panel of leukaemia and lymphoma cell lines (HL60, DoHH2, CEM C7, L1210 and S49), the Baxα-to-Bcl-2 ratio as assessed by Western-blot analysis correlated with sensitivity to dexamethasone treatment. In addition, in HAbaxα-transfected CEM C7 clones, a similar correlation was found for dexamethasone and thapsigargin sensitivity. In bone-marrow aspirates from patients with childhood acute lymphoblastic or myelocytic leukaemia (ALL, n = 48; AML, n = 8), the Bcl-2 and Baxα levels were highly variable, but well within the range found in the Baxα transfectants and in the established cell lines. Bcl-2 levels were lower in T- than in B-lineage ALL, which could be ascribed to simultaneous inverse relation between Bcl-2 and WBC. By contrast, Baxα:Bcl-2 was independent of any presenting feature and was largely dependent on Baxα levels. Results suggest that Baxα:Bcl-2, rather than Bcl-2 alone is important for the survival of drug-induced apoptosis in leukemic cell lines and ALL. Int. J. Cancer 71: 959-965, 1997. © 1997 Wiley-Liss Inc.

Since the introduction of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, children with Hodgkin's disease (HD) have been treated with chemotherapy alone. The occurrence of side effects related to irradiation (especially secondary solid tumors) is less likely to occur. Alkylating agents in the MOPP chemotherapy combinations are, however, known for their late effects, i.e., gonadal dysfunction and secondary malignancies. Combination with non-alkylating and non-cross-resistant drugs (as in the adriamycin, bleomycin, vinblastine, and dacarbazine [ABVD] combination) may give superior treatment results and possibly a decrease in the occurrence of side effects. From 1988 to 1993 all children presenting with HD were treated with alternating MOPP and ABVD courses (3 × MOPP, 3× ABVD). Twenty-one children (7 females, 14 males), ages 5–18 years (median 14 years) were included; their clinical stages were 1, 7 patients; II, 8 patients; III, 5 patients; IV, 1 patient. Their pathology revealed 2 lymphocytic predominance, 17 nodular sclerosis, 1 mixed cellularity. In 1 patient only cytology was done and thus histopathologic subclassification was not possible. Two children have relapsed; disease-free survival is 90%. Analysis of toxicity revealed no decrease in cardiac function by ultrasound examination and no pulmonary effects noted by carbon monoxide diffusion. In 1 of the 10 children tested, mild hypogonadism was noted. No secondary tumors occurred. From this small population of children with HD we conclude that treatment with MOPP/ABVD for 6 cycles without radiotherapy may be adequate. The occurrence of gonadal dysfunction may be less frequent than with 6 cycles of MOPP. However, more patients and further follow-up are needed. Med. Pediatr. Oncol. 29:23–27, 1997. © 1997 Wiley-Liss, Inc.

Accumulating evidence indicates that oxidative modification of low-density lipoproteins is atherogenic and that antioxidants may play a role in protection of LDL against oxidation. Several studies have reported a seasonal fluctuation in antioxidant levels, but to date nothing is known about seasonal fluctuations in parameters of oxidizability. We collected blood from 10 volunteers at four different periods over one year (February, May, September and December), and measured the amount of plasma lip ids, plasma antioxidants, lipid and fatty acid composition of the LDL particle, LDL antioxidant content, LDL particle size and oxidation parameters (lag time and propagation rate). No seasonal fluctuation for lag time and propagation rate of copper ion-induced LDL oxidation was found. Small seasonal fluctuations were observed for some determinants of LDL oxidation, e.g. plasma and LDL vitamin E and LDL particle size, and for plasma lipids, plasma and LDL lutein and LDL p-carotene. Fatty acid composition of LDL did not change during the year. The main determinant of oxidation susceptibility was the fatty acid composition of LDL. We conclude that LDL oxidation parameters do not change over the year.

For T-malignancies in children a poor prognosis is reported. In these malignancies a combination of lymphoma and leukemia is commonly seen at presentation and most patients are treated according to protocols for acute lymphoblastic leukemia (ALL). These protocols are often designed for the majority of ALL cases, i.e., progenitor-B-ALL. In pediatric lymphoblastic non-Hodgkin's lymphoma without bone marrow infiltration various protocols have been used. The most frequently reported regimens show variable survival rates between 40 and 75%. From 1989 we have treated 32 consecutive patients with T-cell malignancies, irrespective of localization, with a protocol consisting of a 4-agent induction treatment followed by high doses of methotrexate, and cytosine-arabinoside and intensified bleomycin, adriamycin, cyclophosphamide, vincristin, prednisone (BACOP) courses. Treatment duration for each patient was 1 year. Twenty-one of the 32 patients had stage IV disease. Follow-up ranged from 1.6 to 7.6 years (median 4.2 years). Overall event-free survival (EFS) was 72%, while in those with stage IV disease it was 67%. No therapy-related deaths occurred. Neither stage, initial leukocyte value, mediastinal involvement, bone marrow involvement, nor the presence of CD1, CD3, CD4, CD8, or CD10 epitopes was prognostically significant. Evaluation of toxicity revealed a minimal decrease of carbon monoxide diffusion and cardiac shortening fraction. A relatively short but intensive chemotherapy can be used in T-cell malignancies. The EFS is satisfying, but larger studies are needed. Med. Pediatr. Oncol. 30:46–51, 1998. © 1998 Wiley-Liss, Inc.

A relatively simple and widely applied method for quantitating the total antioxidant capacity of body fluids and drug solutions based on the absorbance of the ABTS radical cation was evaluated. In this assay, the end-point is an antioxidant-induced decrease in absorbance at a fixed time. This decrease is used as an index of total antioxidant capacity. It is shown that Trolox, potassium cyanide and quercetin all decrease the absorbance of ABTS radical cations at a fixed time, but by different mechanisms. Trolox scavenges the ABTS radical, potassium cyanide inhibits radical formation, while quercetin acts by both mechanisms. Using this method antioxidant capacity may be overestimated, due to both a scavenger effect and an effect on the rate of ABTS oxidation. To distinguish between these effects, a post-addition assay was used in which the sample is added when the formation of radicals is stable. Using post- addition assay conditions enables discrimination between effects on radical scavenging and on the radical formation, two major mechanisms for antioxidant action. In extrapolating the results to an ill vivo situation it should be questioned: (i) whether the peroxidase process does indeed mimic the process of radical formation in vivo, and (ii) whether the ABTS radicals do resemble the radical species involved in an in vivo situation. Results obtained in the ABTS radical-based methods should therefore be reviewed critically before the antioxidant capacity can be assessed.

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