Complete response of congenital fibrosarcoma to chemotherapy.
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Biomedical subjects
Publications and source records attributed to N Delepine.
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We assessed imaging techniques [nuclear, CT, and magnetic resonance (MR)] in the diagnosis of pheochromocytomas in 10 patients with Sipple disease. Nine patients underwent surgery. Magnetic resonance detected all adrenal and ectopic lesions. Metaiodobenzylguanidine scans had two false-negative results. Computed tomography missed an ectopic lesion that was associated with bilateral medullar hypertrophy and had a false-positive result (a cortical nonhyperfunctioning adenoma). In our opinion MR may replace both CT and nuclear scans in the work up of Sipple disease.
BACKGROUND: We aimed to create a model for Ifosfamide (IFX) pharmacokinetics for drug monitoring in order to improve protocol dose intensity. MATERIAL AND METHODS: We studied ifosfamide pharmacokinetics in 12 patients aged 8-19 years. Sixteen courses were modelled (6 g/m2, on 5 days). The auto-induction of ifosfamide was taken into account in the model. Ifosfamide measurement was performed on serum samples by gas chromatography with thermo-ionic detection. Two pharmacokinetic models were compared. The following parameters were estimated: volume of distribution (Vd), clearance at the beginning of the induction (CLi), clearance extrapolated to infinity (CLf), clearance at the end of infusion (CL120), a rate constant (Kc) indicating the clearance variation with time and the lag time (Lag) indicating the time elapsed between the start of infusion and the start of induction. The Wilcoxon test was used to investigate possible differences between models. We tested the hypothesis that Boddy's model is an acceptable simplification of Levy's model. RESULTS: Four of six parameters were significantly different between the two models (p = 0.05). The best curve fitting was obtained using the Levy's model which provided the following estimates, Cli = 2.46 +/- 0.94 L.h-1.m-2, CLf = 5.22 +/- 1.02 L.h-1.m-2, Kc = 0.024 +/- 0.014 h-1, Vd = 18.84 +/- 5.04 L and Lag = 4.86 +/- 6.61 h. The most important difference is found for the distribution volume. CONCLUSION: Levy's model is more accurate and takes into account the integration of clearance.
A study of ACTH response to orally given metyrapone were carried out with 32 normal subjects aged 18 months to 15. Effectiveness of adrenal inhibition was supported by delta F > 5 microgram or cortisol level after metyrapone < 3 microgram/100 ml. The strong positive correlation between delta F and delta ACTH indicates the high sensibility of delta ACTH as an index of the responsiveness. No correlation was found between delta ACTH and weight, height, or age. Mean level (M +/- 2 SEM) are established: plasma ACTH level at 8 before metyrapone = 32,1 +/- 7,5 pg/ml; plasma ACTH level at 8 after metyrapone = 271,8 +/- 57 pg/ml; delta ACTH = 240 +/- 6 pg. Including these considerations, biological ACTH variability, and reproductibility of determinations, an abnormal response seems to be proved by plasma ACTH level at 8 after metyrapone < 100 pg/ml or/and delta ACTH < 70 pg. A normal response is established by delta ACTH > 150 pg.
Study of ACTH responsiveness to oral metyrapone and insulin hypoglycemia in children with repetitive nervous system manifestations (convulsions, coma, mental confusion apathy, tremor) has led to diagnosis of isolated ACTH deficiency in nine children within a three year period. Hypoglycemia was ascertained in five children; in four cases no hypoglycemia was proved, possibly because of promptly disappearance or because of other mechanisms accounting for clinical symptoms (occurrence of intracellular overhydratation associated with corticol deficiency is considered). The incidence of isolated ACTH deficiency in children is possibly undervalued. Reappraisal of isolated ACTH deficiency in childhood as to be considered in idiopathic spontaneous hypoglycemia and perhaps in some paroxysmal neurologic and/or digestive manifestations without proved hypoglycemia and so far poorly defined or held for epileptic fits. In order to disclose further additional tropic hormone deficiencies, and to differentiate permanent from transient impairment of ACTH responsiveness which often seems to be related to emotional deprivation syndrome, more protracted follow up studies are needed.
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This paper evaluates the influence of pharmacokinetics monitoring of HDMTX in the treatment of localized operable previously untreated high grade osteosarcoma. 44 patients (group 1) received a T10 protocol with dose adapted only to age. 27 other patients (group 2) had a pharmacokinetics monitored dose adaptation of MTX. The pharmacokinetics monitoring leads to higher dosage, higher area under the concentration/time curve and permits higher toxicity to be avoided. The higher dose intensity of MTX gave higher histologic response rate (66% compared to 45%) and higher 5 year disease free survival (92% compare to 76%). HDMTX treatment of osteosarcoma should be dose adapted to indivi-dual pharmacokinetics.