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2.
J Med Case Rep ; 15(1): 536, 2021 Oct 25.
Article in English | MEDLINE | ID: mdl-34696819

ABSTRACT

BACKGROUND: In this case report, we describe a very rare case of severe limb ischemia due to an arterial embolus caused by an aneurysm of the oval foramen in a term-born infant that occurred in the first few hours after birth. CASE PRESENTATION: A newborn male Caucasian patient presented on the maternity ward with ischemia of the right foot. Ischemia was treated with nitroglycerin spray and low-molecular-weight heparin in therapeutic dosage. An aneurysm of the oval foramen was found during postnatal echocardiography screening. This was thought to be the source of an embolus causing limb ischemia. At birth and upon follow-up, no clotting disorders were found. A large part of the right forefoot was ischemic, leading to loss of digits 1, 2, and 3. No significant loss of function was found in the first year of life. CONCLUSION: Severe limb ischemia can be caused by an embolus arising from an aneurysm of the oval foramen and can be treated with heparin.


Subject(s)
Aneurysm , Arterial Occlusive Diseases , Foramen Ovale , Aneurysm/complications , Aneurysm/diagnostic imaging , Female , Heparin/therapeutic use , Humans , Infant, Newborn , Ischemia/diagnostic imaging , Ischemia/etiology , Male , Pregnancy
3.
J Glob Antimicrob Resist ; 22: 354-357, 2020 09.
Article in English | MEDLINE | ID: mdl-32251868

ABSTRACT

OBJECTIVES: In the pre-azole era, central nervous system (CNS) infections with Aspergillus had a dismal outcome. Survival improved with voriconazole but CNS infections caused by azole-resistant Aspergillus fumigatus preclude its use. Intravenous liposomal-amphotericin B (L-AmB) is the preferred treatment option for azole-resistant CNS infections but has suboptimal brain concentrations. METHODS: We describe three patients with biopsy-proven CNS aspergillosis where intraventricular L-AmB was added to systemic therapy. Two patients with azole-resistant aspergillosis and one patient with azole-susceptible CNS aspergillosis were treated with intraventricular L-AmB at a dose of 1mg weekly. RESULTS: We describe three patients successfully treated with a combination of intravenous and intraventricular L-AmB. All three patients survived but one patient developed serious headaches, most likely not related to this treatment. CONCLUSIONS: Intraventricular L-AmB may have a role in the treatment of therapy-refractory CNS aspergillosis when added to systemic therapy.


Subject(s)
Amphotericin B , Aspergillus fumigatus , Amphotericin B/pharmacology , Amphotericin B/therapeutic use , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Azoles/pharmacology , Azoles/therapeutic use , Drug Resistance, Fungal , Humans
6.
Int J Pediatr ; 2011: 217564, 2011.
Article in English | MEDLINE | ID: mdl-21876707

ABSTRACT

Objective. To determine the incidence, management, complications, and outcome in neonates with thrombotic events. Study Design. We performed a retrospective study of all neonates with thrombotic events admitted to our neonatal intensive care unit from January 2004 to July 2010. Results. Thrombotic events were identified in 32 of 4734 neonates (0.7%). Seven neonates were managed expectantly and 25 neonates received anticoagulant treatment. Complete resolution of the clot within 3 months of age was found in 68% (17/25) of the treated and in 86% (6/7) of the nontreated neonates. Major complications due to anticoagulant therapy occurred in 3/25 cases (12%) and included severe hemorrhage (n = 2) and abscess at the injection site (n = 1). Conclusion. Complete or partial clot resolution in neonatal thrombosis occurred in both the treated group and nontreated group. Randomized controlled trials are warranted to determine the optimal management in neonatal thrombosis.

7.
J Thromb Haemost ; 9(3): 502-9, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21166992

ABSTRACT

BACKGROUND: Von Willebrand disease (VWD) is the most frequent inherited bleeding disorder. Whether VWD is associated with health-related quality of life (HR-QoL) in children is unknown. OBJECTIVES: This nationwide cross-sectional study measured HR-QoL in children with moderate or severe VWD. Our primary aim was to compare HR-QoL of VWD patients with that of reference populations. Additionally, we studied the impact of bleeding phenotype and VWD type on HR-QoL. METHODS: HR-QoL was assessed with the Infant/Toddler QoL Questionnaire (0-5 years) and Child Health Questionnaire (6-15 years), and compared with reference population scores. Multivariate analysis was used to evaluate the influence of type of VWD and bleeding phenotype on HR-QoL scores. RESULTS: Preschool children (0-5 years, n = 46) with VWD had lower HR-QoL scores for general health perceptions and parental time than reference populations. School children (6-15 years, n = 87) with VWD had lower scores for physical functioning, role functioning - emotional/behavioral, general health perceptions, and physical summary. Type of VWD was associated with HR-QoL in school children for bodily pain, general health perceptions, parental emotion, family activities, and physical summary. Scores of children with type 3 VWD were, on average, 15 points lower than those of the reference population on the above-mentioned scales. A more severe bleeding phenotype was associated with a lower score on 11/15 physical, emotional and social scales. CONCLUSION: HR-QoL is lower in VWD children than in reference populations, in particular in school children. The negative impact of VWD is sensitive to type of VWD and bleeding phenotype; as well as physical scales, emotional and social scales are affected.


Subject(s)
von Willebrand Diseases/physiopathology , von Willebrand Diseases/psychology , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Emotions , Female , Hemorrhage/blood , Humans , Infant , Infant, Newborn , Male , Netherlands , Outcome Assessment, Health Care , Phenotype , Quality of Life , Sociology , Surveys and Questionnaires , von Willebrand Diseases/blood , von Willebrand Diseases/classification
9.
Bone Marrow Transplant ; 31(12): 1081-7, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12796787

ABSTRACT

We reviewed the results of the Dutch paediatric bone marrow transplant (BMT) program for children receiving HLA-identical BMT for beta-thalassaemia major over an 18-year period. In all, 19 patients underwent a total of 21 transplants in our treatment centre between July 1984 and February 2002. Eight females (age 0.3-12 years; median 5 years) and 11 males (age 0.8-18 years; median 6 years) were included. Information, prospectively collected, included molecular defects, donor genotype, beta/alpha-globin expression rates, serum ferritin levels, hepato-splenomegaly, chelation history, virology screening, liver pathology together with post-transplant outcome inclusive of leucocyte chimerism. In total, 11 patients received standard busulphan/cyclophosphamide (Bu/Cy) conditioning, with or without ATG. Stable engraftment was seen in 5/11 with late rejection occurring in six patients. Of these, two children underwent a second successful SCT. For this group, overall event-free survival (EFS) and disease-free survival (DFS) were 90 (10/11) and 64% (7/11), respectively. The probability of rejection was 55%. Subsequent addition of melphalan to the conditioning regimen resulted in long-term stable engraftment in all patients with an EFS/DFS for this group of 90% (9/10). Treatment-related mortality, irrespective of conditioning, was low at 5% (1/19 patients). Veno-occlusive disease (VOD) occurred in 19% (4/21 transplants) and acute GvHD in 19% (4/21 transplants). Post-BMT beta/alpha synthetic ratio measurement monitored donor erythroid engraftment and predicted rejection with a return to transfusion dependency. Maintained full donor chimerism is indicative of stable engraftment both for leucocyte and erythroid lineages, whereas mixed donor chimerism is not. Our results emphasise the importance of the conditioning regimen and post-transplant chimerism surveillance predictive of rejection or long-term stable engraftment.


Subject(s)
Bone Marrow Transplantation , beta-Thalassemia/therapy , Adolescent , Bone Marrow Transplantation/adverse effects , Child , Child, Preschool , Chimera , Disease-Free Survival , Female , Graft Rejection , Graft Survival , Graft vs Host Disease/etiology , Homozygote , Humans , Infant , Male , Netherlands , Transplantation Conditioning/adverse effects , Transplantation, Homologous , beta-Thalassemia/genetics
10.
Leukemia ; 10(8): 1317-25, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8709637

ABSTRACT

Interleukin-7 (IL-7) stimulates the proliferation of normal and leukemic B and T cell precursors and T lymphocytes. Activation of the JAK/STAT pathway has been implicated in IL-7R signaling. We investigated which STAT complexes are formed upon stimulation of B cell precursor acute lymphoblastic leukemia (BCP-ALL) cells with IL-7. Gel retardation assays with STAT-binding oligonucleotides showed that IL-7 induces the formation of two major STAT complexes in BCP-ALL cells. Supershifts with anti-STAT antibodies identified these as STAT1 and STAT5 complexes. This pattern of STAT activation was seen in all BCP-ALL cases that respond to IL-7 in proliferation assays. IL-7 also induced STAT/DNA binding in BCP-ALL cases that failed to proliferate in response to IL-7, suggesting that the ability of IL-7R to activate the JAK/STAT pathway per se is not sufficient for proliferation induction. To determine the contribution of the cytoplasmic domain of the IL-7 receptor alpha chain (IL-7R alpha) to activation of STAT proteins, transfectants of the murine pro-B cell line BAF3 were made that express chimeric receptors consisting of the extracellular domain of human granulocyte colony-stimulating factor receptor (G-CSF-R) and the transmembrane and intracellular domains of human IL-7R alpha. Activation of the chimeric G-CSF-R/IL-7R alpha with G-CSF resulted in a full proliferative response and induced the phosphorylation of JAK1 but not JAK2. Major STAT complexes activated by G-CSF-R/IL-7R alpha contained STAT1 or STAT5, while some formation of STAT3-containing complexes was also seen. These findings establish that STAT1 and STAT5, and possibly STAT3, are activated upon stimulation of precursor B cells with IL-7. The data further indicate that the IL-7R alpha chains are directly involved in the activation of JAKs and STATs and have a major role in proliferative signaling in precursor B cells.


Subject(s)
Antigens, CD/physiology , B-Lymphocytes/physiology , DNA-Binding Proteins/metabolism , Interleukin-7/pharmacology , Milk Proteins , Precursor Cell Lymphoblastic Leukemia-Lymphoma/physiopathology , Proto-Oncogene Proteins , Receptors, Interleukin/physiology , Signal Transduction , Trans-Activators/metabolism , Animals , Antigens, CD/biosynthesis , Antigens, CD/chemistry , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Base Sequence , Burkitt Lymphoma/immunology , Burkitt Lymphoma/physiopathology , Cell Line , DNA Primers , Enzyme Activation , Humans , Janus Kinase 1 , Janus Kinase 2 , Kinetics , Macromolecular Substances , Mice , Molecular Sequence Data , Polymerase Chain Reaction , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Protein-Tyrosine Kinases/metabolism , Receptors, Granulocyte Colony-Stimulating Factor/biosynthesis , Receptors, Interleukin/biosynthesis , Receptors, Interleukin/chemistry , Receptors, Interleukin-7 , Recombinant Fusion Proteins/biosynthesis , STAT1 Transcription Factor , STAT5 Transcription Factor , Signal Transduction/drug effects , Thymidine/metabolism , Tumor Cells, Cultured
11.
Br J Haematol ; 93(1): 125-30, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8611444

ABSTRACT

Activation of CD20, a cross-membrane ion channel, induces cell cycle progression from G0 to G1 in B lymphocytes. Subsequent activation of CD40, a membrane receptor of the nerve growth factor receptor superfamily, transits the B cells to the S phase. CD40 may also act synergistically in combination with IL-4 (B lymphocytes) or IL-3/IL-7 (B-cell precursors). We investigated the proliferative responses of B-lineage acute lymphoblastic leukaemia (ALL) cells to CD20/CD40 activation. In 18/56 ALL cases, CD20 activation resulted in significant increases in DNA synthesis. Similar, although more moderate, effects were seen of activation of CD40 in 10/44 cases. Responses to CD20 or CD40 activation were independent of co-stimulation with IL-3, IL-4 or IL-7, and various cocktails of the different growth stimuli did not act synergistically.


Subject(s)
Antigens, CD20/immunology , Burkitt Lymphoma/immunology , CD40 Antigens/immunology , DNA/biosynthesis , Cell Division/immunology , Flow Cytometry , Humans , Interleukin-3/pharmacology , Interleukin-4/pharmacology , Interleukin-7/pharmacology , Tumor Cells, Cultured
12.
Leukemia ; 9(6): 1039-45, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7596167

ABSTRACT

Interleukin 7 (IL-7) stimulates proliferation of normal human and murine B cell precursor (BCP) cells in a distinct fashion, depending on the stage of maturation of the cells. For instance, the productive rearrangement of the immunoglobulin heavy chain gene has been demonstrated to be essential for the response of BCP cells to IL-7 as the single proliferation stimulus. IL-7 activates a receptor that consists of the IL-7R protein and the common gamma chain (gamma c). BCP acute lymphoblastic leukemia (BCP-ALL) cells variably respond to IL-7. Among 72 cases of BCP-ALL IL-7 activated DNA synthesis in 34. In four cases inhibition of DNA synthesis was seen. In the remaining 38 cases IL-7 exerted no effects. We determined whether this heterogeneity in IL-7 response could be correlated with parameters that could influence the IL-7 response. Firstly we show that, in contrast to the murine BCP cells, the IL-7 response of human BCP-ALL cells did not correlate with the status of IgH chain gene rearrangement and expression, nor with the rearrangement of IgL chain genes. Subsequently, it is demonstrated that IL-7R protein and transcripts as well as gamma c transcripts are equally present in the IL-7 responsive and nonresponsive BCP-ALL samples, indicating that the defective expression of these chains could not be held responsible for IL-7 response failures. Finally, we observed that kit ligand (KL), known to synergize with IL-7 in the most primitive stages of normal B cell development, did not enhance the IL-7 responses of BCP-ALL cells.


Subject(s)
Antigens, CD/biosynthesis , Burkitt Lymphoma/genetics , Burkitt Lymphoma/immunology , Gene Expression , Genes, Immunoglobulin , Interleukin-7/pharmacology , Receptors, Interleukin-2/biosynthesis , Receptors, Interleukin/biosynthesis , Animals , Base Sequence , Bone Marrow/pathology , Burkitt Lymphoma/pathology , Cell Division/drug effects , DNA Primers , Gene Rearrangement , Humans , Macromolecular Substances , Mice , Molecular Sequence Data , Polymerase Chain Reaction , Receptors, Interleukin-4 , Receptors, Interleukin-7 , Transcription, Genetic , Tumor Cells, Cultured
13.
Biochem Biophys Res Commun ; 209(3): 989-95, 1995 Apr 26.
Article in English | MEDLINE | ID: mdl-7537502

ABSTRACT

The lactase-phlorizin hydrolase gene is widely used as a marker of intestinal differentiation. Recent evidence demonstrating that transcription plays a major role in the regulation of this gene suggests that study of the 5'-flanking region will allow an understanding of how the expression of this gene is controlled. However, sequence, restriction, and primer extension analysis of a rat genomic clone has revealed that previously published data are incomplete. In the present study, we used a directed sequencing strategy to carefully analyze this region. Our expanded analysis of the 5'-flanking region of the lactase-phlorizin hydrolase gene should facilitate future studies of its structure and function.


Subject(s)
Genes, Regulator , Jejunum/enzymology , Lactase-Phlorizin Hydrolase/genetics , Promoter Regions, Genetic , Rats/genetics , Animals , Base Sequence , DNA Primers , Genomic Library , Lactase-Phlorizin Hydrolase/biosynthesis , Molecular Sequence Data , RNA/genetics , Restriction Mapping , TATA Box , Transcription, Genetic
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