Biomedical subjects
Publications and source records attributed to F Millot.
The authors review 29 toes transfers on 24 patients with injury of long fingers between 1985 and 1990. The series contains 16 complete toes and 13 partial toes transfers. The results, inconvenience and indications are discussed.
A multicenter prospective study was conducted in 114 children with acute lymphoblastic leukemia receiving 4 intravenous methotrexate (MTX) courses (5 g/m2 as a 24 hour-infusion) to determine the diffusion of MTX in cerebrospinal fluid (CSF) and to correlate the drug levels to central nervous system (CNS) relapse occurrence. Serum and CSF levels were measured at the end of 446 MTX courses. A significant correlation was found between CSF and serum MTX concentration. CSF MTX level was greater than 1 mumol/l in 66% of the courses. Twelve patients (11%) failed to achieve this potentially cytotoxic drug level at the end of the 4 consecutive MTX courses: only one CNS relapse was observed and the mean age of these children was lower than that of the others. To date 9 (7.8%) children had CNS relapse and no difference was observed in terms of CSF MTX levels when compared to data of children free of CNS relapse. With a median follow up of 32 months, pharmacokinetic data during high-dose MTX therapy do not seem to be an exclusive predictive factor of CNS relapse.
The authors report on 6 cases for which an emergency toe partial transfer was performed for the reconstruction of a thumb or long finger digital segment. In most cases, toe pulp transfer was involved, but also partial composite pulp-bone-nail transfers. Such technique, whose indications seldom apply in an emergency, gives better results than conventional techniques (such as homo- and hetero-digital flaps or distant flaps).
Concentrations of 2,4-diamino-7-hydroxy-pteridines in plasma and cerebrospinal fluid (CSF) are reported for the 0.5-8 g/m2 dose range of methotrexate in children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma. This experiment has revealed that: (1) there is a wide inter-individual but relatively narrow intra-individual variability of the maximal concentrations of 2,4-diamino-7-hydroxy-pteridines in plasma during consecutive methotrexate cycles; (2) the increase in the level of the metabolites in plasma was related to increments of the methotrexate dose, but not above 5 g/m2: this can be explained by a saturable conversion of methotrexate to 2,4-diamino-7-hydroxy-pteridines; (3) significant correlations were found between simultaneous values of 2,4-diamino-7-hydroxy-pteridines in plasma and CSF; (4) the formation of 2,4-diamino-7-hydroxy-pteridines did not depend on the ages of patients receiving the same dose of methotrexate. The presence of these compounds in plasma and CSF in significant amounts creates the potential for a number of competitive interactions with pteridine-dependent metabolism which may open up new possibilities for understanding the metabolic side-effects of methotrexate therapy.
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Cerebrospinal fluid (CSF) neopterin levels were determined by high-pressure liquid chromatography in 48 normal children and in 15 children with meningeal relapse of hematologic malignancies (13 acute lymphoblastic leukemia and 2 high-grade lymphomas). When meningeal relapse was diagnosed, all patients had CSF neopterin levels higher than mean normal value +2 standard deviations. No significant correlation between the blast count in the CSF and neopterin levels was observed. CSF data before relapse were available in 10 children: the neopterin values at relapse were significantly higher than values observed at diagnosis. In 3 patients, elevated neopterin levels preceded the occurrence of neurologic signs and the detection of blast cells in CSF by 15 to 30 days. In the absence of infection, the rise of CSF neopterin levels in patients with hematologic malignancies indicates an active phase of the disease. This could reflect a cell-mediated immunologic process induced by malignant cells. The measurement of CSF neopterin should be helpful in the monitoring of patients to detect early meningeal relapse.
The pronator quadratus m. can be raised as a flap on its main anterior interosseous pedicle, whose characteristics are as follows: diameter of the artery 2.1 mm, diameter of the each of both veins 2.4 mm, length of useful pedicle 70-80 mm, after possible intraneural dissection of the nerves to the flexor pollicis longus m.
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A transient acute neurologic syndrome occurred in a 15-year-old boy receiving high-dose methotrexate (MTX) for acute lymphoblastic leukemia. Cerebrospinal fluid analysis revealed a decrease of homovanillic acid and 5-hydroxyindoleacetic acid concentrations with a rise of biopterin levels. These findings suggest that MTX can induce a transient alteration of the metabolism of tetrahydrobiopterin leading to the defect of biogenic amine neurotransmitter synthesis.
BACKGROUND: Cardiac metastases from malignant tumors are rare in children and are usually found only at necropsy. CASE REPORT: A girl aged 6 months developed a swelling in the area of her left shoulder. Surgical excision was incomplete and pathological examination indicated neuroectodermic soft-tissue tumor. Chemotherapy with cyclophosphamide, doxorubicin then vincristine and actinomycin D was instituted, followed by second course of cyclophosphamide-doxorubicin. Three months after cessation of chemotherapy, the child developed manifestations of congestive cardiac failure that could not be induced by anthracycline (total cumulative dose: 275 mg/m2). Cardiac ultrasonography showed a metastatic tumor (diam = 3 cm) on the wall of the right ventricle and atrium, which was pedunculated inside the infundibular chamber. It was partly excised, and the patient was treated with etoposide and carboplatin. But a second metastatic tumor formed in the paravertebral area. CONCLUSION: This is the first description, to our knowledge, of cardiac metastases from neuroectodermic tumor. They were diagnosed by cardiac ultrasonography, as this imaging technique differentiates this complication from the anthracycline-induced cardiomyopathy usually seen in children developing cardiac failure under chemotherapy.
Methotrexate remains a commonly used drug in the chemotherapy of various malignancies. The known catabolites are 7-hydroxy-methotrexate, formed in the liver, and diamino-methyl-pteroic acid formed in the gut. We report for the first time evidence that 2,4-diamino-7-hydroxy-pteridine derivatives are present in the biological fluids of patients on high-dose methotrexate protocols. So far, two major derivatives have been identified as 2,4-diamino-6-hydroxymethyl-7-hydroxy-pteridine and 2,4-diamino-6-methyl-7-hydroxy-pteridine. In regard to the actual knowledge of the catabolism of pteridines, these compounds are presumably formed by intestinal bacteria during enterohepatic circulation of the drug. Their slow clearance from the body raises the question of possible interference of these compounds on pteridine-dependent enzymes, which might explain in part some of the toxic effects of methotrexate.
Plasma and follicular fluid (FF) hormone assays for follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), oestradiol (E2), progesterone (P), delta-4-androstenedione (A4) and testosterone (T) were performed on the day of oocyte retrieval in two groups of normo-ovulatory women enrolled in an in-vitro fertilization (IVF) programme: 24 were treated using the decapeptyl agonists DTRP6, of luteinizing hormone-releasing hormone (LHRH) in the long protocol associated with human menopausal gonadotrophin (HMG) (49 FF) and 14 were stimulated with HMG alone (33 FF). In both FF and plasma the mean concentration of P was greater, and the E2/P ratios as well as the LH levels were lower in the agonist-treated group. In this group the follicular concentration of P was greater and the E2/P ratio lower when pregnancy occurred following IVF. The hormonal modifications may be due to greater functional maturity of the granulosa cells.
A case of acute non lymphoblastic leukemia in a 9 year-old girl is reported. This case presented with intracranial hypertension with exophthalmos and parietal subcutaneous tumor; imaging techniques showed their subcutaneous, orbital and intracranial localizations. Complete remission was obtained within 7 months with polychemotherapy. The rare cases of granulocytic sarcoma of central nervous system in children are reviewed.
The occurrence of increased levels of blood phenylalanine after therapeutic administration of folate analogues has been occasionally reported and attributed to the inhibition of dihydropteridine reductase, an enzyme maintaining the cofactor of phenylalanine hydroxylase in its active tetrahydrogenated form (tetrahydrobiopterin). To study further this metabolic effect, 46 patients receiving high dose methotrexate (5 to 8 g/m2) infusions have been studied. Significant increase in serum phenylalanine was observed in 95% of methotrexate cycles, occurring at the end of infusion. In contrast to the large inter-individual variations, maximal phenylalanine concentrations were of the same magnitude in each individual, suggesting individual predispositions. The hypothesis of an inhibition of dihydropteridine reductase by methotrexate was supported by the parallel course of serum biopterin and phenylalanine levels, but in some way contradicted by the rapid return to baseline values of both, 24 hours after the end of methotrexate infusion. This transient and often moderate hyperphenylalaniemia is probably harmless except if it reflects a more general inhibition of pteridine-dependent hydroxylases. Especially, such an inhibition of cerebral tyrosine- and tryptophan-hydroxylase activities might be the reason for transient neurological disturbances observed in some patients on high-dose methotrexate treatment.
We report a patient who developed a bone and adjacent soft tissue malignancy 22 months after bone marrow transplantation (BMT) for Philadelphia chromosome positive chronic myelogenous leukemia (CML). Concomitant bone marrow was cytologically and cytogenetically normal. Cytogenetic study of tumoral tissue was unsuccessful but DNA analysis revealed BCR-AB1 rearrangement similar to that observed in hematopoietic cells prior to BMT. The present case demonstrates that molecular analysis is helpful in the diagnosis of unusual relapse of CML.
Thirty cases of digital avulsions caused by a ring have were reviewed after a period of eighteen months. The average age of the patients was 30 years, ranging from 5 to 60 years. Fourteen vascular survivals were obtained. In this series the ring finger was the most frequently affected one (21 cases). In 20 cases, the people involved were long distance lorry drivers. The operating techniques were direct micro arterial and venous anastomosis in 2 cases, and isolated arterial bypass grafts in 6 cases, combined arterial and venous bypass graft in 18 cases. No surviving finger was amputated, but 3 patients, including 2 women, asked the amputation of an unsightly stump. This series confirms the extreme seriousness of digital avulsion caused by rings and the value of a microsurgical treatment of vascular lesions by anastomosis or by arterial and venous bypass grafts from stage 2 onwards.
Acute monocytic leukaemia (AMoL) was diagnosed in 99 adults, aged 18-85 years (median 56) over a period of 10 years. Sixty-five patients had extramedullary leukaemia, 13 had clinical signs of leucostasis, and 19 had disseminated intravascular coagulation. Four patients died before receiving any treatment, 12 received supportive care only and seven received low dose AraC, but only one of them responded. Seventy-six patients received intensive chemotherapy, 72 of them with an anthracycline-AraC based regimen, with or without an epipodophyllotoxin. Fifteen patients died within 7 d of diagnosis, due to leucostasis in nine cases. Predictive factors for early death were advanced age, leucostasis, fever, leucocytes above 100 x 10(9)/l, and renal failure. Fifty (66%) of the patients treated intensively reached complete remission (CR). Advanced age, fever and complex cytogenetic abnormalities were significantly associated with a lower CR rate. Median actuarial disease-free survival was 20.5 months, and was not significantly influenced by any pretreatment parameter. Five patients relapsed in the central nervous system (CNS), in spite of systematic CNS prophylaxis. No differences in CR rates were seen with the three anthracycline-AraC based regimens used in our patients. Significant differences in disease-free survival were seen between them, however, suggesting that early consolidation chemotherapy and, more hypothetically, epipodophyllotoxin agents could prolong remission duration in AMoL.
The lateral brachial flap is a septo-cutaneous flap raised from the lateral surface of the arm. It is a thin and reliable flap with a neurovascular pedicle and its donor site can be self-closing in the case of small flaps. The authors report six cases of closure of hand defects by means of this flap, including one case of emergency repair. Due to its simplicity, the lateral brachial flap now constitutes one of the alternatives for cover of hand defects and its pedicled version may be useful cover of the elbow region.