[Cardiogenic shock due to acute mitral dysfunction after deep venous thrombosis]. / Schock durch akute Mitralklappendysfunktion mit schwerer Insuffizienz nach Beinvenenthrombose.

Open surgical embolectomy may be life-saving in massive pulmonary embolism. Up to now there are no studies concerning the question whether the foramen ovale should be examined routinely during surgery and whether an open foramen ovale should be closed routinely in the same session. Even case reports regarding this question are missing. We report on a 74-year old female patient who developed pulmonary embolism due to deep venous thrombosis. Six days after successful surgical embolectomy the patient developed cardiogenic shock due to a huge thrombus from the right atrium through the foramen ovale into the left atrium and the left ventricle. Immediate surgical embolectomy of a 40-50 cm huge thrombus was successful. Immediately after surgery upon the cardiac mass the patient showed symptoms of acute right leg ischemia. Thus a second embolectomy was necessary, the surgeon removed a 10 cm thrombus from the right external iliacal artery. There was no evidence of another pulmonary embolism timely related to the paradoxical embolism.

ATM gene and lymphoid malignancies.

Inherited biallelic mutations of the ATM (ataxia-telangiectasia mutated) gene cause ataxia-telangiectasia, a rare autosomal recessive disorder associated with a high incidence of childhood leukaemias and lymphomas, suggesting that ATM gene alterations may be involved in lymphomagenesis. Loss of heterozygosity at 11q22-23 (location of the ATM gene) is a frequent event in sporadic lymphoid tumours, and several studies have reported a high prevalence of ATM gene alterations in diverse sporadic lymphoproliferative disorders, adding evidence to the postulated contribution of ATM in the pathogenesis of these tumours. This mini-review will summarize the recently published data concerning the ATM gene in sporadic lymphoid malignancies and will discuss the apparent paradox between the predominance of nonsense mutations observed in patient with ataxia-telangiectasia and the high proportion of missense alterations found in sporadic lymphoid tumours.

ALK-positive anaplastic large-cell lymphoma: strong T and B anti-tumour responses may cause hypocellular aspects of lymph nodes mimicking inflammatory lesions.

The anaplastic large cell lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma which occurs in children mostly. The ALK protein is highly immunogenic and elicits both humoral and cellular immune responses. A 15-yr-old child presented with fever and adenopathy and did not respond to antibiotics. Biopsy of the enlarged lymph node contained almost no lymphoid element except for a few CD8-positive T cells, plasma cells and isolated CD30-positive blasts. The patient's condition improved following lymphadenectomy but relapse occurred 3 months later with multiple nodes, high fever and an abdominal mass. This time an ALK-positive ALCL was diagnosed and the retrospective analysis of the initial biopsy revealed rare, isolated ALK+ cells. Molecular analysis showed T-cell clones and oligoclonal B cells in both biopsies and peripheral blood of the patient. The tumour cells harbour a t(2;5) translocation, revealing a null phenotype by immunohistochemistry and no evidence for T-cell clonality by Southern blotting. The patient's serum contained anti-ALK antibodies. Our findings suggest that the T-cell clones and anti-ALK antibodies in this patient constitute an anti-tumour response that caused the hypocellularity of the initial lymph node. Hypocellular and oedematous lymph nodes occurring in a child with evocative symptoms should be tested for the presence of ALK.

Intellectual outcome in children and adolescents with acute lymphoblastic leukaemia treated with chemotherapy alone: age- and sex-related differences.

One of the most relevant concerns in long-term survivors of paediatric acute lymphoblastic leukaemia (ALL) is the development of neuropsychological sequelae. The majority of the published studies report on patients treated with chemotherapy and prophylactic central nervous system (CNS) irradiation, little is known about the outcome of patients treated with chemotherapy-only regimens. Using the standardised clinical and neuropsychological instruments of the SPOG Late Effects Study, the intellectual performance of 132 paediatric ALL patients treated with chemotherapy only was compared to that of 100 control patients surviving from diverse non-CNS solid tumours. As a group, ALL and solid tumour survivors showed normal and comparable intellectual performances (mean global IQ 104.6 in both groups). The percentage of patients in the borderline range (global IQ between 70 and 85) was comparable and not higher as expected (10% cases and 13% controls, expected 16%). Only 2 (2%) of the former ALL and 1 (1%) of the solid tumour patients were in the range of mental retardation (global IQ<70). Former known risk factors described in children treated with prophylactic CNS irradiation, like a younger age at diagnosis of ALL and female gender, remained valid in chemotherapy-only treated patients. The abandonment of prophylactic CNS irradiation and its replacement by a more intensive systemic and intrathecal chemotherapy led to a reduction, but not the disappearance of late neuropsychological sequelae.

Analysis and quantification of prescribing and transcription errors in a paediatric oncology service.

OBJECTIVE: To analyse and quantify the omission errors linked to physicians' prescribing and errors linked to nurses' transcription and to identify the type and frequency of factors associated. No pharmacological factors are taken into account. DESIGN: Analysis of physicians' prescriptions and nurses' transcriptions in chemotherapeutic treatments (20 patient files) and non-chemotherapeutic treatments (20 patient files); retrospective study. SETTING: Paediatric onco-haematology unit. MAIN OUTCOME MEASURES: Categorisation of physicians' prescriptions as complete or incomplete, categorisation of the various nurses' transcriptions as correct or incorrect. RESULTS: Physicians' prescriptions were complete for 61.6% of non-chemotherapy treatments. As each prescription is transcribed twice, two nurses' transcription sheets are filled in by the nurses. At the first transcription 79.3% of non-chemotherapy prescriptions and 88.2% of chemotherapy prescriptions were transcribed correctly, while in the second sheet these percentages were respectively 96.2% and 93.7%. CONCLUSIONS: Too many sheets of paper generate confusion and increase the risk of errors. The several transcriptions are, in both types of treatment, sources of errors. The problems identified in this study allowed us to open a discussion as how to improve the physicians prescriptions and the nurses' transcription sheets.

Successful treatment of neonatal rhesus hemolytic anemia with high doses of recombinant human erythropoietin.

The authors report the use of high-dose recombinant erythropoietin (r-HuEPO) in a full-term newborn baby with severe postnatal rhesus hemolytic anemia (RHA). Hemoglobin (Hb) value and reticulocyte count at day 13 of life were 59 g/L and 234 x 10(9)/L, respectively. Three days after the r-HuEPO (870 U/kg/d) administration, reticulocyte count had increased more than 4-fold and Hb rose to 73 g/L. r-HuEPO was gradually decreased after 18 days of treatment. No major side effect was observed. In selected cases of severe anemia due to hemolytic disorders, transfusions may be avoided by the use of high doses of r-HuEPO.

Cidofovir for cytomegalovirus infection and disease in allogeneic stem cell transplant recipients. The Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

A retrospective study was performed to collect information regarding efficacy and toxicity of cidofovir (CDV) in allogeneic stem cell transplant patients. Data were available on 82 patients. The indications for therapy were cytomegalovirus (CMV) disease in 20 patients, primary preemptive therapy in 24 patients, and secondary preemptive therapy in 38 patients. Of the patients, 47 had received previous antiviral therapy with ganciclovir, foscarnet, or both drugs. The dosage of CDV was 1 to 5 mg/kg per week followed by maintenance every other week in some patients. The duration of therapy ranged from 1 to 134 days (median, 22 days). All patients received probenecid and prehydration. Ten of 20 (50%) patients who were treated for CMV disease (9 of 16 with pneumonia) responded to CDV therapy, as did 25 of 38 (66%) patients who had failed or relapsed after previous preemptive therapy and 15 of 24 (62%) patients in whom CDV was used as the primary preemptive therapy. Of the patients, 21 (25.6%) developed renal toxicity that remained after cessation of therapy in 12 patients. Fifteen patients developed other toxicities that were potentially due to CDV or the concomitantly given probenecid. No toxicity was seen in 45 (61.6%) patients. Cidofovir can be considered as second-line therapy in patients with CMV disease failing previous antiviral therapy. However, additional studies are needed before CDV can be recommended for preemptive therapy.

Hypothesis for generation of the unstable Hb Bucuresti (beta 42 Phe-->Leu) mutation.

INTRODUCTION: Unstable hemoglobin disorders are characterized by a congenital, mostly familial chronic hemolytic anemia with episodes of severe hemolysis during febrile illnesses. Usually, isopropanol and heat stability tests lead to the diagnosis which is confirmed by protein and gene sequencing. Generation of the mutations is still a subject of controversy. PATIENT, MATERIALS AND METHODS: We describe a 6-year-old Swiss child with congenital hemolytic anemia and a negative family history. Hemoglobin was studied by IEF, HPLC reverse phase chromatography, heat stability and isopropranol tests. DNA was sequenced in both coding and non-coding strands. RESULTS: An unstable Hb was diagnosed on the basis of positive heat stability and isopropranol tests. The TTT-->TTG mutation at codon 42 corresponding to a Phe-->Leu substitution was found on DNA sequencing. Paternity was confirmed indicating that we are dealing with a new mutation. CONCLUSION: So far, three different mutations at codon 42 of the beta-chain, and two at the corresponding position of the alpha-chain have been described, all leading to a hemolytic anemia. These mutations can either represent random phenomena occurring at an important location in the heme pocket, or may be secondary to the two highly homologous zones present in this region. These homologous zones may indicate a hot spot for point mutations created by abnormal crossing over or formation of loops, and an imperfect DNA repair process.

Fatal myocardial aspergillosis in an immunosuppressed child.

A girl with resistant acute myeloid leukemia (AML) had a stem cell transplantation. Preceding transplantation, she had recurrent pneumonitis. No causative agent was identified. Despite several antibiotics including high-dose liposomal amphotericin-B, pulmonary infection progressed. Aspergillosis, always considered, could not be documented. She died from cardiac arrest on the second day after transplantation, with no forewarning of previous heart disease. Pericardial and myocardial aspergillosis was an autopsy finding. Pericardial and myocardial aspergillosis, rare manifestations of systemic aspergillosis, should be considered in any immunocompromised patient with long-lasting pulmonary infection, even in the absence of specific cardiac findings.

Trimethoprim-sulfamethoxazole salvage for refractory listeriosis during maintenance chemotherapy for acute lymphoblastic leukemia.

A 5-year-old boy with acute lymphoblastic leukemia (ALL) and intolerance to oral trimethoprim-sulfamethoxazole (TMP/SMX) had Listeria monocytogenes bacteremia and meningitis develop during maintenance chemotherapy. Despite prompt administration of IV amoxicillin/gentamicin and microbiologic clearance of the bloodstream, the patient had no response to therapy after a course of 7 days. Intravenous TMP/SMX (10 mg/kg per day of TMP) was added to the antibiotic regimen after desensitization. Fever and meningeal signs rapidly resolved, and the patient was ultimately cured. Amoxicillin and gentamicin, although highly active and synergistic in vitro against L. monocytogenes, have limited intracellular penetration and activity. In contrast, TMP/SMX has bactericidal extracellular and intracellular activity against Listeria and excellent central nervous system penetration, and thus may be effective for the treatment of refractory listeriosis.

Prognostic value of cerebrospinal fluid cytology in pediatric medulloblastoma. Swiss Pediatric Oncology Group.

BACKGROUND: Although the demonstration of leptomeningeal dissemination is the most important predictor of poor outcome in children with medulloblastoma, there is lack of consensus on the prognostic value of a positive cerebrospinal fluid (CSF) cytology (i.e., stage M1). PATIENTS AND METHODS: Eighty-six pediatric medulloblastoma patients treated in Switzerland between 1972-1991 were retrospectively studied regarding the influence of M-stage on prognosis. 39 were M0, 13 M1, 15 Mx, 17 M2, and 2 M3. RESULTS: Five- and 10-year overall survival rates were 76% and 54% for M0, 68% and 50% for Mx, 36% and 25% for M1, and 22% and 22% for M2-3 (P < 0.001), respectively. No significant survival differences were observed between M1 and M2-3 patients. Among 26 patients with only postoperative CSF cytologies, seven were positive. Their outcome was similar to that of six preoperatively staged M1 and significantly different from that of M0 patients (P = 0.001). In 14 patients both pre- and postoperative CSF cytology was performed. Total agreement was observed between the pre- and postoperative results (six positive and eight negative). Among the 19 M2-3 patients CSF cytology was positive in eight, negative in five, and unknown in six. CONCLUSIONS: A positive CSF cytology either pre- or postoperatively predicts for a poor outcome, similar to that observed in stage M2-3 patients. A postoperative cytology is likely to be concordant with cytologic results obtained preoperatively, and seems to have the same prognostic significance. A negative cytology, however, does not exclude a more advanced stage.

[Common anemias in neonatology]. / Häufige Anämien in der Neonatologie.

We describe the four most common groups of neonatal anemia and their treatments, with particular emphasis on erythropoietin therapy. The hemolytic anemias include the ABO incompatibility (much more frequent, nowadays, than the Rh incompatibility, which has nearly disappeared following the use of anti-D immunoglobulin in postpartum Rh-negative mothers), hereditary spherocytosis and G-6-PD deficiency. Among hypoplastic anemias, that caused by Parvovirus B19 predominates, by far, over Diamond-Blackfan anemia, alpha-thalassemia and the rare sideroblastic anemias. "Hemorrhagic" anemias occur during twin-to-twin transfusions, or during feto-maternal transfusions. Finally, the multifactorial anemia of prematurity develops principally as a result of the rapid expansion of the blood volume in this group of patients. Erythropoietin therapy, often at doses much higher than those used in the adult, should be seriously considered in most cases of non-hypoplastic neonatal anemias, to minimise maximally the use of transfusions.