[The hemolytic uremic syndrome: prime reason for acute renal failure in children]. / Le syndrome hémolytique et urémique. Première cause d'insuffisance rénale aiguë de l'enfant.

The Hemolytic Uremic Syndrome (HUS) is the prime cause for acute renal failure in children. The HUS is a combination of hemolytic anemia, thombopenia and acute nephropathy: all signs of a thrombotic microangiopathy. Onset occurs generally in infancy and is often associated with severe bloody diarrhea. Most of those cases are caused by Escherichia coli O157:H7 witch produces an exotoxin responsible for the microangiopathy. We discuss the treatment of HUS based on the experience acquired since 1994 in our Paediatric Intensive Care Unit (PICU), University of Liege. The frequent association of dehydration, multi-systemic impairment and reno-vascular hypertension justifies the early admission for PICU-surveillance. This allows the difficult fluid balance management in a setting of renal and pre-renal failure.

[Clinical case of the month. A recurrent chylothorax in Bourneville tuberous sclerosis]. / Le cas clinique du mois. Un chylothorax récidivant dans un contexte de sclérose tubéreuse de Bourneville.

Bourneville's disease, first described in 1862, is a phacomatosis that is either autosomal dominant or sporadic. Its typical clinical signs include mental retardation, epilepsy and cutaneous adenomas. The pulmonary form is rare, less than 1%, and is secondary to occlusion of the bronchus, vascular and lymphatics by immature smooth muscle cells. Chylothorax may appear in more than 50% of all cases. No guidelines currently exist for treatment of recurrent chylothorax. However, several possibilities are described in the literature.

Long-term results of three randomized trials (58831, 58832, 58881) in childhood acute lymphoblastic leukemia: a CLCG-EORTC report. Children Leukemia Cooperative Group.

We present here the long-term results of three randomized clinical trials conducted on children with newly diagnosed acute lymphoblastic leukemia (ALL) between 1983 and 1998 by the Children Leukemia Cooperative Group (CLCG) from EORTC. In study 58831/32, the overall event-free survival (EFS) rates (+/- s.e.) at 6 and 10 years were 66% +/- 1.8% and 65% +/- 1.8%, respectively, and the risk of isolated central nervous system (CNS) relapse was 6% +/- 1% and 7% +/- 1%, respectively. In patients with a standard risk of relapse the omission of cyclophosphamide had no adverse effect on disease-free survival rates at 10 years (trial 58831). In medium- and high-risk patients the omission of radiotherapy did not increase the risk of CNS or systemic relapse (trial 58832). In study 58881 (1989-1998) the overall EFS rate at 8 years was 68.4% +/- 1.2% and the risk of isolated CNS relapse was 4.2%+/-0.5%. In this trial which adressed three randomized questions, the following results were obtained: the combination of cytarabine at high doses with methotrexate at high doses during interval therapy did not improve prognosis. The addition of 6-mercaptopurine iv during maintenance increased the risk of late relapse. E. coli asparaginase was more toxic and has a higher efficacy than Erwinia asparaginase. Leukocyte counts >100 x 10(9)/l, specific genetic abnormalities, a poor initial response to steroids or a high level of minimal residual disease at early time points were consistently associated with an adverse prognosis in the 58881 trial.

[Treatment of urinary infections in children. Pharmaco-economic aspects]. / Traitement des infections urinaires de l'enfant. Aspects pharmaco-économiques.

The risk factors for urinary tract infections in children are the young age, the severe febrile symptoms, any obstruction or dilatation of the urinary tract, recurrent episodes of acute disease and delay in initiating effective treatment. Today a new risk factor lies in the increasing resistance of germs to usually used antibiotics. The treatment therefore must be adapted to the local patterns of bacterial sensitives. To lower cost of the therapy, different ways may be followed: 1. To try to reduce the time of the inpatient management by using day-care or outpatient management possibilities. 2. To try to switch from the initial, heavy parenteral drugs to antibiotics to which the germ is sensitive and even to an adapted oral medication, when the child is doing well, is well hydrated and can tolerate the treatment. The outpatient management requires more compliance from the child and may be a burden for the parents.

[Chronic visceral leishmaniasis during chemotherapy for metastatic osteosarcoma]. / Leishmaniose viscérale chronique au cours d'une chimiothérapie pour ostéosarcome métastatique.

UNLABELLED: Leishmaniasis refers to a spectrum of diseases caused by Leishmania. Clinically, three types of leishmaniasis can be distinguished: the cutaneous, mucous and visceral leishmaniasis, the latter being caused by Leishmania donovani. CASE REPORT: An 11-year-old Thai, living in Belgium for 6 years, had surgery for a vertebral osteosarcoma with pulmonary metastases, followed by polychemotherapy, then pulmonary metastasectomy. During a post-chemotherapy bone marrow aplasia, febrile episode with a general condition impairment was noted and first treated by broad-spectrum antibiotherapy, then by amphotericin B, in the absence of any accurate etiology. The outcome first was favorable. Nevertheless, 7 months later, the visceral leishmaniasis diagnosis was made because of the recurrence of the same symptoms. Classical treatments by antimony derivatives (Glucantim), then liposomal amphotericin (Ambisome) proved to be inefficient. A liposomal amphotericin-gamma interferon association suppressed the symptoms without eradicating the parasite. The patient was given a maintenance therapy based on liposomal amphotericin. CONCLUSION: The stubborn and recurring nature of this chronic visceral leismaniosis can be due to the immune deficit inherent in the polychemotherapy performed in order to treat the metastatic osteosarcoma which currently is in first full remission.

[Sickle cell anemia in children: value of hydroxyurea in severe forms]. / Anémie falciforme chez l'enfant: intérêt de l'hydroxyurée dans les formes graves.

BACKGROUND: Sickling of red cells in patients with sickle cell anemia causes painful vaso-occlusive crises (VOC). Hydroxyurea (HU) has been shown to increase HbF production and therefore has the potential to prevent these crises in adult patients. This work aimed to confirm its clinical efficiency in children. PATIENTS AND METHODS: Since 1993, eight children and adolescents (5-16 years old) with hemoglobinopathy (HbS > 65%) were given HU (14 to 27 mg/kg/day) for a mean duration of 10 months. We did a retrospective study about different data, especially inpatient days for VOC, pain intensity during these crises, individual transfusion requirements and HbF level. RESULTS: As the HbF levels increased, we observed a reduction of the inpatient days for VOC, of the pain intensity during these crises and of the mean number of units transfused per month. CONCLUSION: HU is the first clinically acceptable drug shown to prevent painful crises in adults but also in children with sickle cell anemia. However, its effects and potential toxicity are still unknown and the other therapeutic possibilities have to be considered before starting a long-term treatment with HU.

Cutaneous involvement in children with acute lymphoblastic leukemia or lymphoblastic lymphoma. The Children's Leukemia Cooperative Group of the European Organization of Research and Treatment of Cancer (EORTC).

OBJECTIVE: Skin involvement in children with acute monocytic leukemia or CD30-positive anaplastic large-cell lymphoma is well-known. In contrast, very little is known about the malignant cutaneous infiltrates in children with acute lymphoblatic leukemia (ALL) or lymphoblastic lymphoma (LBL). This study was designed to determine the frequency of these specific lesions in childhood ALL or LBL and the characteristics of such patients. DESIGN: We studied the clinical and biological findings of children with cutaneous involvement at initial diagnosis of ALL or LBL enrolled between August 1989 and March 1995 in the multicentric trial 58881 of the Children's Leukemia Cooperative Group of the European Organization of Research and Treatment of Cancer (EORTC). RESULTS: Among the 1359 children enrolled in the multicenter trial EORTC 58881, 24 presented with skin involvement at diagnosis. ALL was diagnosed in 15 patients and LBL in 9. In 15 cases, skin lesions were observed within a median time of 6 weeks (range, a few days to 8 months) before the diagnosis of the hematologic disease. Twenty-one children had at least one skin lesion located on the head. Diffuse cutaneous lesions were observed in 7 infants with high-risk ALL. Seventeen of the 24 children remain in the first complete remission (median follow-up of 3 years; range 2 months to 5 years) and 3 are in the second remission with a follow-up of 14 to 24 months. CONCLUSION: The present study demonstrates that cutaneous involvement can be an early manifestation of ALL or LBL. Cutaneous leukemic infiltrates can be observed in children with standard risk as well as in high-risk ALL. Cutaneous involvement in children with LBL is mainly associated with a B-cell precursor immunophenotype of the lymphomatous cells. The most frequent location of skin lesions in children with ALL or LBL is on the head. Further studies are needed to evaluate the prognosis of children with such involvement at diagnosis.

Systemic effect of intrathecal methotrexate during the initial phase of treatment of childhood acute lymphoblastic leukemia. The European Organization for Research and Treatment of Cancer Children's Leukemia Cooperative Group.

PURPOSE: The in vivo response to prephase corticosteroid therapy for 1 week has been described as a major prognostic factor in childhood acute lymphoblastic leukemia (ALL). Patients with less than 1,000 blasts/microL at day 8 are considered responders and have a better prognosis. This prephase therapy is usually considered as an evaluation of glucocorticoid sensitivity. In fact, it also includes one intrathecal (IT) injection of methotrexate (MTX). In this study, we try to clarify the influence of this injection of IT MTX on the response to the prephase therapy. PATIENTS AND METHODS: This retrospective study analyzed the response to prephase therapy in 1,044 children with ALL entered onto the European Organization for Research and Treatment of Cancer (EORTC) trial 58881 of the Children's Leukemia Cooperative Group (CLCG). Analysis was restricted to 732 cases with an initial blast count greater than 1,000/microL. The following variables were tested to analyze response to prephase therapy: age, sex, evaluated risk factor (RF), blast count on day 0, actual dose of prednisolone administered, immunophenotype (T v non-T), and day of IT MTX. For statistical analysis, the variable day of IT MTX (D) was stratified into three groups: group 1 if D less than 2, group 2 if D > or = 2 but < or = 6, and group 3 if D greater than 6. RESULTS: All variables tested had a significant influence on response to the prephase therapy. This was especially true for IT MTX: 90.4% responders in group 1, 76.9% in group 2, and 70% in group 3 (P < .001). Immunophenotype was also a major predictor of response to the prephase: 88% responders in B-lineage ALL versus 56.2% in T-lineage ALL. IT MTX had a significant influence in B-lineage ALL (96% responders in group 1, 90% in group 2, and 79% in group 3; P < .001), whereas the influence could not be detected in T-lineage ALL. CONCLUSION: These results clearly demonstrate a therapeutic systemic effect of low doses of IT MTX in childhood ALL, and response to prephase therapy should not be considered as an in vivo test for cortico-sensitivity only. Earlier use of IT MTX leads to a higher percentage of responders.

Possible pathogenic role of IgE in Henoch-Schönlein purpura.

The incidences of clinical and biological markers of atopy were investigated in 16 children with IgA nephropathy (IgAN) (group A) and in 22 with Henoch-Schönlein purpura nephritis (HSPN) (group B). The incidence of increased plasma IgE levels according to age-matched normal values was significantly higher in group B (17/22, 77%) than in group A (7/16, 44%) (P < 0.05). Although not significant, the incidences of positive RAST tests and of a history of typical atopic symptoms were also higher in group B [10/22 (45%) and 11/22 (50%), respectively] than in group A [4/16 (25%) and 5/16 (31%), respectively]. Moreover, IgE deposits were demonstrated by a peroxidase/anti-peroxidase method on cutaneous Langerhans and mast cells in 4 of 6 patients with HSPN. Thus immunoallergy might account, in some cases, for the cutaneous, intestinal and pulmonary signs observed in HSPN, but not in IgAN. We postulate stimulation of IgE-sensitized mast cells by specific antigens in the presence of IgA circulating immune complexes (CIC), release of vasoactive substances, increased capillary permeability and perivascular deposition of IgA CIC.

Treatment of acute lymphoblastic leukemia in children with the BFM protocol. A cooperative pilot study.

From January 1981 through July 1983, 141 children with newly diagnosed acute lymphoblastic leukemia were registered in a cooperative clinical study whose objective was to evaluate the toxicity and the feasibility of the German Berlin-Frankfort-Münster (BFM) protocol. The results were comparable with those reported by the BFM group. For the 133 patients (94%) who achieved complete remission, the actuarial disease-free survival was 67% at 4 years. These results were obtained in spite of a high rate of deaths in complete remission during the initial year of the study. Subsequently, probably as a result of improved expertise in the handling of the protocol, the proportion of toxic deaths declined sharply. Although the current BFM protocol adjusts for aggressiveness of therapy according to the volume of the liver and spleen, splenomegaly (but not hepatomegaly) remained of prognostic significance. Moreover, for patients with bad risk features, an initial high hemoglobin level was found to represent an additional factor of negative significance.

A Rothmund-Thomson case with hypertension.

An unusual association of Rothmund-Thomson syndrome and hypertension is described. The histologic studies showed large narrowing and calcification of arteries at renal biopsy, thickenings of glomerular basement membranes and nodules of subendothelial basement membrane lamellae in arterioles by means of electron microscopy. The mechanisms of these morphologic alterations are discussed with regard to disturbances of collagenous and fundamental substances of metabolism.

Abnormalities of erythrocyte stromal lipids in atresia of the intrahepatic bile ducts.

Detailed analysis of plasma and erythrocytes lipid composition of patient with intrahepatic biliary atresia is presented. Abnormalities have been outlined and are characterized as following: (1) an increase of total cholesterol compounds and total phospholipids in serum; (2) an increase of free cholesterol and lecithin up to 50 per cent of total phosphatides in red cells; (3) the fatty-acids pattern isolated from total phospholipids of red cells shows a rise of palmitic and palmitoleic acids and a decrease of stearic and longer-chain fatty acids; (4) in PC and PE of red cells, there is an overall tendency for the degree of unsaturation of long-chain fatty acids to increase. In addition to these lipid changes, it was demonstrated by polyacrylamide-gel electrophoresis that the composition of membrane proteins was normal. It is of particular interest to establish whether these abnormalities are either induced by complex metabolic pathways and exchange processes between the lipids of circulating erythrocytes and the altered lipids of serum environment or are the direct result of modified hepatic cellular or enzymatic function.