Biomedical subjects
Publications and source records attributed to M Bonduel.
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To determine guidelines for administering and monitoring acenocoumarol therapy in children, 93 patients (median 5.1 years, range: 0.2-18 years) were prospectively evaluated over a 33-month period. The loading doses used were: <1 year, 0.20 mg x kg-1; >1-5 years, 0.09 mg x kg-1; 6-10 years, 0.07 mg x kg-1; 11-18 years, 0.06 mg x kg-1. In this study, the loading dose and the dose to achieve and maintain target therapeutic range (TTR) for acenocoumarol are age-dependent, with infants having the highest and teenagers having the lowest requirements. The use of a different loading dose according to age has allowed most of the children (80%) in all the age groups to achieve TTR in less than 1 week. No patients had serious bleeding or thrombotic complications. We conclude that there is an age-dependent response to acenocoumarol in pediatric patients. The implementation of an age-adjusted loading dose regimen reduces the length of hospitalization required to achieve effective anticoagulant therapy.
BACKGROUND: T-cell depletion (TCD) of BM allows transplantation across HLA barriers. Although different methods are used throughout the world, the optimal application of TCD still remains unclear, partly due to the lack of thorough analyses of the cellular fractions eliminated or retained in each method, and their possible implications regarding GvHD, GvL, or engraftment. We have analyzed the phenotype of the successive fractions of 19 BM samples depleted by soybean lectin agglutination and sheep erythrocyte rosetting (elimination of T cells that form rosettes through CD2), focusing on the final fraction infused to patients. METHODS: Analysis was performed using three-color flow cytometry and strategies for optimal staining and individualism of the subsets of interest. RESULTS: The relative composition of the lymphoid population varied significantly along the successive steps in TCD: at the agglutination step, B cells and CD4 T cells are greatly reduced, while natural killer cells (NK) and TCRgammadelta+ T are augmented. The rosetting steps imply the relative enrichment of CD2-dim T cells, together with a further rise in the proportion of NK and double-negative T cells frequently TCRgammadelta+. DISCUSSION: The presence of minor subsets of CD2- TCRgammadelta+ and CD2- TCRalphabeta T cells has already been described in the peripheral blood of normal individuals. We report that, by using this method of TCD, CD2-dim T cells, frequently TCRgammadelta+, are retained in the grafts and infused in patients, together with NK cells as the main lymphoid population. We discuss the possible implications of these populations in the biology of the graft, regarding GvHD, GvL and engraftment.
We report two patients who developed atypical skin lesions caused by Curvularia sp. and Pseudallescheria boydii after allogeneic bone marrow transplantation for severe aplastic anemia. The first patient (female, 18-year-old) had multiple hemorrhagic vesicles on day +30 after her second BMT for graft failure. Pseudallescheria boydii was isolated from a skin biopsy. The patient died of respiratory failure probably as a consequence of systemic fungal infection. The second patient (male, 9-year-old) developed an ecthyma gangrenosum-like lesion on his right palm on day +8. Curvularia sp. was isolated from a skin biopsy. Liposomal amphotericin was given to achieve a total dose of 30 mg/kg and followed by oral itraconazole until steroids were discontinued. The infection resolved completely and the patient has remained disease-free. We conclude that emerging fungal organisms such as those described in this report are increasingly recognized in this setting. Early recognition and biopsy of these cutaneous lesions will allow prompt initiation of therapy to prevent systemic infection.
BACKGROUND AND PURPOSE: Moyamoya syndrome is an uncommon chronic occlusive cerebrovascular disease in children. The origin of moyamoya syndrome remains undetermined. The role of the prothrombotic disorders contributing to its pathogenesis has not been completely elucidated. The purpose of this study was to determine the frequency of prothrombotic disorders in a pediatric population with moyamoya syndrome. METHODS: From May 1992 to April 2000, a prospective study of 10 consecutive children with moyamoya syndrome was carried out at a single center. Evaluation included the following assays: protein C, protein S, antithrombin, plasminogen, activated protein C resistance, factor V Leiden, and prothrombin gene mutations. Lupus anticoagulant, anticardiolipin antibodies, and anti-beta(2)-glycoprotein I antibodies assays were also performed. The clinical characteristics, underlying diseases, family history of thrombosis, radiological findings, treatment, and outcome were also recorded. RESULTS: In our series, prothrombotic disorders were detected in 4 patients (40%). Inherited protein S deficiency was found in 1 patient; lupus anticoagulant and anticardiolipin antibodies were detected in the remaining 3 patients. One presented persistent lupus anticoagulant for 2.7 years until his death. In the case of the other 2 patients, 1 has maintained lupus anticoagulant for 9 months, whereas the other has kept anticardiolipin/anti-beta(2)-glycoprotein I antibodies for 10 months. CONCLUSIONS: We report the hemostatic data of the largest prospective pediatric study carried out at a single center in the western hemisphere. In 4 patients (40%), a prothrombotic disorder was detected. It is tempting to speculate that these hemostatic abnormalities may contribute to the pathogenesis of moyamoya syndrome in some of our patients.
BACKGROUND: Arterial ischemic stroke (AIS) and sinovenous thrombosis (SVT) are relatively rare events in children. The contribution of prethrombotic disorders to the etiology of these entities has not been completely elucidated. OBJECTIVES: To determine the frequency of inherited and acquired prethrombotic disorders in a pediatric population with AIS and SVT and to report clinical and radiological features. METHODS: From May 1992 to April 1997, 30 consecutive children with AIS and 10 children with SVT were assisted at a single institution. Hemostatic evaluation was performed for all the children. Evaluation included the following assays: protein C, protein S, antithrombin, plasminogen, activated protein C resistance, factor V Leiden mutation, and the detection of antiphospholipid antibodies. Data concerning baseline demographics, risk factors, presenting features, family history of thrombosis, and radiological findings were also recorded. RESULTS: One or more prethrombotic disorders were present in 9 children (30%) with AIS (inherited protein S deficiency, 2 patients; inherited protein C deficiency, 1 patient; acquired antithrombin deficiency, 2 patients; antiphospholipid antibodies, 3 patients; and antiphospholipid antibodies and plaminogen deficiency, 1 patient) and in 5 children (50%) with SVT (inherited protein S deficiency, 1 patient; acquired antithrombin deficiency, 3 patients; and antiphospholipid antibodies, 1 patient). CONCLUSIONS: Most children studied presented both a variety of risk factors for thrombosis and concomitant prethrombotic disorders. Therefore, a complete hemostatic evaluation for all children with AIS and SVT should be performed, despite the presence of obvious clinical risk factors or lack of family history of thrombosis.
Major histocompatibility complex (MHC) class II deficiency is a rare form of primary combined immunodeficiency that can only be corrected by stem cell transplantation. We report a 4(1/2)-year-old girl with MHC class II deficiency who underwent a related CBT due to graft failure following T cell-depleted non-identical BMT. The patient is alive and well 2 years after the second transplant. A sustained hematopoietic engraftment and a progressive immune recovery have been detected. We conclude that cord blood may be an effective source of hematopoietic stem cells for patients with immuno- deficiency disorders including diseases with a high rate of graft failure.
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Idiopathic myelofibrosis (MF) is a rare disease in childhood. The clinical spectrum is very variable. Familial idiopathic MF has been recorded exceptionally. In previous reports idiopathic MF in childhood has been described in association with congenital anomalies and with chromosome abnormalities, although neither of these features have been reported in a familial context. We report two sisters with idiopathic MF and multiple eruptive hemangiomas. Details of their clinical signs, laboratory findings, and histologic features are described.
Severe aplastic anemia is a hematological disease with a high mortality rate, for which bone marrow transplantation is the treatment of choice, specially in children and young adults. The number of transfusions undergone before the transplant is the most important factor to predict the possibility of graft failure. Twenty patients with severe aplastic anemia, most of them already multiple transfused, were transplanted utilizing cyclophosphamide combined with antilymphocyte globulin as a conditioning regiment. All the evaluable patients engrafted and there were no episodes of graft failure. Three patients died, and 17 (85%) are alive with hematopoietic recovery at a median of 27.7 months post-transplant. Bone marrow transplantation was an excellent therapeutic option in this series of patients with severe aplastic anemia and the conditioning regiment appeared to be sufficiently myeloablative and immunosuppressive to avoid early or late graft failure.
This study was designed to identify the beta-thalassemia mutations in an Argentine population. Seventy-one pediatric patients and 101 available relatives were studied (85 chromosomes). Diagnosis of beta-thalassemia was made by conventional hematological procedures. Molecular studies were carried out by dot-blot and restriction endonuclease analysis on amplified DNA to detect the eight most frequent mutations in the Mediterranean area. We were able to identify 95.3% of the beta-thalassemia mutations in the subjects under study. The four common defects (C-39, 47%; IVS-I nt 110, 22.4%; IVS-I nt 1, 9.4%; and IVS-I nt 6, 5.9%) account for 84.7% of the beta-thalassemia alleles. The alleles and their distributions showed a close similarity to the spectrum of alleles in Italy. The differences might represent the influence of other immigrations, especially from Spain. We conclude that beta-thalassemia in Argentina originated mainly from Italian immigrants. This study will enable us to design an adequate approach to genetic counseling and/or prenatal diagnosis for couples at risk.
A 4-year-old boy with chronic myeloid leukemia (CML) was shown to have a variant Ph t(Y;22)(p11;q11). To our knowledge, this is the first report of a variant Ph translocation involving Y. Molecular analysis showed that the breakpoint on chromosome 22 is in the breakpoint cluster region (bcr), typical of CML with the classic t(9;22), suggesting that it might be a complex Ph translocation with the involvement of 9q34.
We report a 13-year-old boy with hereditary deficiency of protein S, who developed a deep vein thrombosis of the lower limb after a varicella with severe cutaneous lesions. Hereditary protein S deficiency is an established cause of thrombophilia; however thrombotic events are seldom described in pediatric patients. A review of previous literature revealed 35 cases, 16 girls and 19 boys, with a first episode below of the age of 18 years old (x = 10y). The 57% of the patients had venous thrombosis, 20% arterial thrombosis, and 14% both and in 9% the type of thrombosis was not reported. Predisposing factors were referred in only 12 cases. The deficiencies can be classified as type I in 25 patients and type III in 8.
PURPOSE: The aim of this study was to determine the frequency of acquired or inherited prothrombotic disorders in a pediatric population with venous thromboembolism (VTE). PATIENTS AND METHODS: From May 1992 to April 1998, 56 consecutive children with VTE were prospectively studied at a single center. RESULTS: The median age was 8.4 years (range, 0.1-18 years). There was a male predominance. Fifty (89%) children had thrombosis in the lower venous system. Risk factors were detected in 54 (96%) children. Twenty-one (38%) thrombotic episodes were related to central venous lines. Family history of thrombosis was positive in 13 (23%) patients. In 26 (46%) patients, a prothrombotic disorder was detected. Nine of them had inherited disorders (protein C deficiency, 5 patients; protein S deficiency, 3 patients; Factor V Leiden mutation, 1 patient), and 13 children had acquired disorders (antiphospholipid antibodies, 5 patients; antithrombin deficiency, 8 patients). The remaining four showed combined abnormalities (Factor V Leiden mutation associated with inherited protein S deficiency, 1 patient; acquired antithrombin deficiency, 2 patients and inherited antithrombin deficiency, 1 patient). CONCLUSIONS: In the series, a high percentage of prothrombotic disorders was detected; thus, a complete hemostatic evaluation should be performed in all of the children with VTE whether the patients have one or more risk factors.