Thrombolysis with recombinant tissue-type plasminogen activator in renal venous thrombosis in infancy.
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Humans↗
Biomedical subjects
D Schwabe
Publications and source records attributed to D Schwabe.
Metaiodobenzylguanidine (mIBG) in treatment of 47 patients with neuroblastoma: results of the German Neuroblastoma Trial.
From 1984 to 1989, 47 children with relapsed, refractory, and/or metastasized neuroblastoma were treated with 131I-metaiodobenzylguanidine (mIBG) in several different treatment combinations. At initial diagnosis, 36 children had Evans stage IV and 11 stage III disease. In 16 of the 47 children, tumor recurred after complete remission prior to mIBG treatment, 26 of 47 progressed from residual or nonresponding tumor, and in 5 of 47 tumor progression during chemotherapy was observed. Altogether the children were treated with a total of 112 courses (range 1-6) with a mean dosage of 8.9 +/- 6.7 mCi/kg body weight/treatment course. Total dose was 283.2 +/- 203.7 mCi for stage III and 388.9 +/- 218.6 mCi for stage IV. Nine of 47 children reached a complete or a very good partial remission (CR and VGPR) from mIBG treatment alone, 13 of 47 achieved partial remission (PR). In an early analysis, 10 patients treated with mIBG in the neuroblastoma trial NB 85 of the German Society of Pediatric Oncology showed no significant difference in survival time compared with 30 conventionally treated children. However, the recent therapy series has been done with higher doses of mIBG, and during improved therapeutic scanning many more bone lesions could be detected than during earlier diagnostic scanning. We conclude that mIBG treatment has not yet fulfilled the expectations for it but still seems for certain indications to be a promising tool to treat neuroblastoma in the future. Moreover, the frontier of neuroblastoma detection is still advancing.
3-Iodobenzylguanidine↗
Differences in air ambulance patient mix demonstrated by physiologic scoring.
Severity of illness or injury should be the primary justification for aeromedical transport. To determine whether differences in patient severity were detectable in air transport programs, helicopter-transported patients were examined by three established physiologic scores: the Trauma Score, the Acute Physiology and Chronic Health Evaluation Score, and the Rapid Acute Physiology Score. These scores were obtained prospectively on 1,868 consecutive patient transfer requests from six air medical services for periods ranging from two to six months. A patient meeting strict physiologic criteria was considered critically ill. Overall, 42.6% of the patients (range, 34.8% to 53.3%) were considered critically ill. Patients transported from inpatient hospital units and patients with cardiac disease were less likely to be critically ill than those transported emergently from scenes of accident or from emergency departments. There were also significant differences between programs with regard to the percentage of critically ill patients transported. This study suggests that physiologic scoring may be useful in comparing air ambulance programs and that a majority of patients transported by these services may not be critically ill.
Aircraft↗
APACHE II scoring in the injured patient.
The purpose of this study was to measure the predictive power of Acute Physiology and Chronic Health Evaluation (APACHE II) with respect to mortality in a group of seriously injured patients and to compare this predictive power with that of the Trauma Score (TS) and the Injury Severity Score (ISS). Six hundred ninety-one helicopter-transported patients were studied. Individual logistic regressions demonstrated that all three scores had significant predictive power when considered individually (TS chi 2 = 136, p less than .0001; APACHE II chi 2 = 171, p less than .0001; ISS chi 2 = 109, p less than .0001). In addition, each severity score added significantly to the predictive power in a stepwise logistic regression (TS chi 2 = 15, p less than .0001; APACHE II chi 2 = 45, p less than .0001; ISS chi 2 = 15, p less than .0001). Areas under the receiver operating curves for the three scores were not significantly different (TS 0.8116, SD 0.0245; APACHE II 0.8515, SD 0.0204; ISS 0.7967; SD 0.0223). APACHE II is a good predictor of mortality, and its predictive power is complemented by TS and ISS.
Adolescent↗
Rapid acute physiology scoring in transport systems.
A multi-institutional study was undertaken to define the predictive power for mortality of the Rapid Acute Physiology Score (RAPS) in a large and diverse group of transported patients. RAPS is a truncated version of the Acute Physiology and Chronic Health Evaluation (APACHE II) score that uses definitions and weighting consistent with APACHE II, but is modified to provide a consistent score just before transport, just after transport, and to use the most deranged (worst) physiologic values during the initial 4 h after arrival at the receiving hospital. During an 8-month period, 1,927 patients transported by six helicopter emergency medical service programs were studied. Over 97% (1,881) of the patients had RAPS obtained before and after transport to the receiving hospital and 92.6% (1,785) had APACHE II scoring completed after hospital admission. Receiver operating curves demonstrate similar predictive power for RAPS and APACHE II (both based on the most deranged physiologic values during the initial 24 h after admission). Before- and after-transport RAPS were also highly predictive of mortality. RAPS appears to be a reliable and highly predictive measure of patient severity/physiologic stability before and after transport to critical care.
Adult↗
Determination of m-iodobenzylguanidine in serum and urine by high-performance liquid chromatography.
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3-Iodobenzylguanidine↗
Chromosome translocation (2;13)(q37;q14) in a disseminated alveolar rhabdomyosarcoma.
Chromosome analysis of tumour cells in the bone marrow of a 13.5-year-old girl (without a primary tumour) revealed a pseudo-diploid or pseudo-tetraploid karyotype with a translocation involving the long arms of chromosomes 2 and 13: t(2;13)(q37;q14). This finding enabled the diagnosis of a disseminated alveolar rhabdomyosarcoma (RMS) to be established. The patient was treated by cytotoxic chemotherapy, went into complete remission, but died of relapse 14 months after diagnosis. As several cases with this translocation have been described recently, this additional report confirms that t(2;13) is specific for the alveolar subtype of RMS.
Adolescent↗
MIBG-treatment in neuroblastoma; experiences of the Tübingen/Frankfurt group.
27 children with neuroblastoma were treated with 131I-Metaiodobenzylguanidine (MBIG). They were either refractory to conventional therapy or experienced relapse after initially successful treatment. 7 children revealed stage IV and 20 stage III at the beginning of MIBG-treatment. MIBG was administered by infusion lasting from 30 min to 30 hrs. In most children the dose was split into two portions each infused over a period of 4 hrs with a 24 hrs interval between. Courses were repeated up to 6 times and maximum activity given to one patient cumulatively was 38,221 MBq. 24 patients were evaluable for analysis of results. In 4 children (16.7%) a CR was observed, in 10 (41.7%) a PR, in 5 (20.8%) a disease stabilization and 5 were nonresponders. The 4 CR-patients were initially stage IV. 3 of them were treated in addition by bone marrow transplantation (bmt), one by further chemotherapy. 3 died of a relapse, 1 of complications from bmt. 5 of the 10 PR-patients died of tumor progression, 3 achieved a CR by additional chemotherapy, 1 a PR by bmt and 1 stays in PR without further measures. 2 of the 5 children with a disease stabilization were the first treated patients to whom a fairly low dose was given. In 3 of the 5 nonresponders no uptake of MIBG was observed; they died from tumor progression. 1 of the 2 nonresponders with uptake died of graft-versus-host disease after bmt, 1 other also of tumor progression. Duration of remission was between 1 and 12 months and depended upon uptake and dose of MIBG, interval between administrations and individual tumor behaviour. Side effects were seen as marked bone marrow depression; this was reversible in any case and we did not loose a patient due to MIBG-induced leuko- or thrombopenia. In cases of severely ill children we observed a very fast and dramatical amelioration in clinical conditions. With this method even in neuroblastoma relapse and in nonresponders complete remissions are achievable. Important is the intensification of the therapeutical effect by additional chemotherapy or in combination with bmt. For a definitive evaluation further investigations are necessary to optimize therapeutic strategies.
3-Iodobenzylguanidine↗
131-Metaiodobenzylguanedine therapy of neuroblastoma in childhood. One year of therapeutic experience.
Eleven children with neuroblastoma refractory to conventional therapy or relapse of neuroblastoma were treated with 131-metaiodobenzylguanedine (MIBG). The therapeutic results and the side effects were evaluated. In one patient with disseminated bone marrow involvement complete remission was obtained. Partial remission was observed in six patients and stable disease in another. Three patients did not respond to MIBG, in two of them the tumours did not accumulate a sufficient MIBG dose. Clinical and laboratory examinations revealed an excellent tolerance of MIBG in all patients. First attempts to continue cytostasis after MIBG therapy were made. MIBG has a good therapeutic efficacy is sufficiently incorporated into the tumour cell.
3-Iodobenzylguanidine↗
Immunochemical aspects, molecular and kinetic properties of multiple forms of acetyl-CoA acetyltransferase from rat liver mitochondria.
Acetyl-CoA acetyltransferase (EC 2.3.1.9) from rat liver mitochondria, which catalyzes the first step in the biosynthesis of ketone bodies, exists in two forms, designated transferase A and transferase B. Both transferases showed immunochemical cross-reactivity, but are immunologically unrelated to cytosolic acetyl-CoA acetyltransferase activity and the mitochondrial acetyl-CoA acyltransferase from rat liver. The transferases A and B were estimated to have molecular weights of 151 000 in the absence and 40 000 in the presence of sodium dodecyl sulfate. They differ with respect to charge states and multiplicity of forms as indicated by isoelectric focusing. Transferase A appeared in two forms with isoelectric points of 8.4 and 9.1, whereas transferase B represents a stable protein state with an isoelectric point of 9.0. Kinetic analysis of the reactions leading to acetoacetyl-CoA synthesis revealed saturation curves with multiple intermediary plateaus, indicating a complex kinetic behaviour. The data presented are interpreted as representing a microheterogeneity of forms of the mitochondrial acetyl-CoA acetyltransferase. The kinetic properties exhibited suggest a role for this microheterogeneity in the regulation of ketogenesis.
Acetyl-CoA C-Acetyltransferase↗
Ex vivo expansion of highly purified NK cells for immunotherapy after haploidentical stem cell transplantation in children.
BACKGROUND: Allogeneic natural killer (NK) cells are known to show medium to high cytotoxic activity against HLA-nonidentical leukemia or tumor cells. For a possible benefit of post transplant treatment with NK cells after haploidentical stem cell transplantation (haplo-SCT) we developed a clinical scale procedure for NK cell processing observing Good Manufacturing Practice (GMP). METHODS: Allogeneic donor NK cells were selected from 15 unstimulated leukaphereses using two rounds of immunomagnetic T cell depletion, followed by an NK cell enrichment step. CD56 (+)CD3 (-) NK cells were stimulated and expanded in vitro according to GMP. Quality control of NK cell purity, residual T cells and cytotoxic activity was done by multi-coloured flow cytometric analyses. RESULTS: Purification led to an absolute number of 234-1 237 x 10 (6) CD56 (+)CD3 (-) NK cells from leukapheresis harvests with a median purity of 95 % and a 4 to 6(1/2) log depletion of T cells. After two weeks stimulation with IL-2 a five-fold expansion of NK cells with a T cell contamination below 0.1 % was reached. Median cell viability was 95 % after purification and 99 % after expansion. The IL-2 stimulated NK cells showed a highly increased lytic activity against the MHC-I deficient K562 cells compared to freshly isolated NK cells and a medium cytotoxicity against patients' leukemic cells. CONCLUSIONS: Clinical scale enrichment and activation of allogeneic donor NK cells is feasible. High dose NK cell application may be a new treatment option for pediatric patients with leukemia or solid tumors in case of minimal residual disease or unbalanced chimerism post haplo-SCT as we could show for the first three patients .
Antigens, CD19↗
[High dosage methotrexate in combination with "8 in 1" in therapy of pediatric grade III/IV brain tumors].
20 patients with malignant brain tumors in childhood were treated according to a regimen which included initial surgery, preradiation chemotherapy and subsequent irradiation. The chemotherapy consisted of alternating cycles of high-dose methotrexate (12 g/m2) and "8 drugs in 1 day" (Bleyer, 1983). Each cycle was to be given up to six times, as tolerated. The diagnoses were medulloblastoma in 10 cases, astrocytoma in 5 cases, ependymoma and PNET in 2 patients each, and malignant mesenchymoma in 1 case. 15 patients were previously untreated, 5 patients experienced relapse after a different first line therapy and a longer time interval. 8 patients are in continuous complete remission for 13 to 54 months. The toxicity upon the bone marrow, the kidney and the inner ear was tolerable. Long lasting emesis contributed a marked problem to the patients but did not cause abbreviation of the therapy. The neurotoxicity was notably mild. Three episodes of generalized seizures were seen without subsequent sequelae, four cases of peripheral neuropathy were attributable to vincristine. A leukoencephalopathy was neither detected on clinical grounds nor on neuroradiological imaging. Therapy related deaths were not seen. We conclude that the combination of HD-MTX and "8 in 1" markedly contributes to the intensification of the chemotherapy for malignant brain tumors in childhood. In the setting as preradiation chemotherapy the toxicity is tolerable.
Adolescent↗
[Thrombolysis with rt-PA in children with arterial and venous thromboses--a new therapy concept].
Thrombolytic therapy usually used for thrombosis in the adult has been administered as a therapeutic regiment in pediatric patients (parental consent was sought prior to the treatment with rt-PA). We report our experience with rt-PA in 17 children and adolescents suffering from arterial (n = 4) or venous thrombosis (n = 13) due to local rhabdomyosarcoma, acute lymphoblastic leukemia, chronic myeloblastosis, sickle cell anaemia, parenteral nutrition, haemolytic uremic syndrome, central arterial and venous catheters and septicemia Thrombotic diseases have been diagnosed by Doppler ultrasound, computed tomography, angiography and phlebography. Rt-PA therapy was started immediately after diagnostic procedures had been performed. Rt-PA dose varied from 0.2 mg as a single dose to 0.8 mg/kg bw/d over a three day period in children local thrombolysis was performed. In patients requiring systemic thrombolytic therapy rt-PA was administered from 0.8 mg/kg bw/d in three days to 2.0 mg/kg bw/d over a whole period of three weeks in both groups during thrombolysis low dose heparin was added. When rt-PA infusion was terminated heparin (70 IU - 400 IU/kg bw/d) was administered for 7 to 14 days in order to prevent reocclusion. Later prophylaxis with coumarin derivatives in venous thrombosis and antiplatelet agents in arterial occlusive diseases was performed. In no patient did we see a decrease of fibrinogen and plasminogen during rt-PA therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Prevention of cytomegalic inclusion disease in leukemia patients with a cytomegalovirus hyperimmune globulin preparation].
In a randomised study the efficacy of a cytomegalic hyperimmune globulin preparation (CMV-HIGP) which had been treated with beta-propiolactone was analysed. The study included 85 patients with acute lymphoblastic leukemia (ALL) and Non-B-Non-Hodgkin-lymphoma (NHL) who were treated initially or underwent a relapse therapy. During the intense chemotherapeutical period within leukemia treatment the patients were passively immunised by the intravenous route with CMV-HIGP (1 ml per kilogram of body weight) every two to three weeks at the latest. In the initial stages the basic immunisation protection was achieved by the application of double dose CMV-HIGP. The Frankfurt patients were recruited from the BFM-ALL- and the NHL-study since october 1982. When they were admitted their CMV serostatus was determined by means of the ELA-ELISA or IFA-method. Seronegative patients were given the passive immunisation immediately or 48 hours after the first blood transfusions at the latest. The patients who had become CMV-IgG-positive by passive immunisation were randomised when reaching long-term therapy according to the protocol. Because of a 30% cytomegaly disease incidence rate in our patient population a randomisation was unwarrantable at the beginning of leukemia treatment. During randomisation one group of patients were immunised by the intravenous route with CMV-HIGP (2 ml per kg body weight one time in four weeks), the second group was a control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Child↗
[Initial experiences in the treatment of children with metastatic and recurrent neuroblastoma using meta-iodobenzylguanidine].
At four involved hospitals 16 children were treated with Metaiodobenzylguanidine (131J-MIBG). These children had a relapse of neuroblastoma stage III or IV or did not respond sufficiently to chemotherapy. In 10 children extreme bone pain disappeared and they became free of fever during the MIBG-treatment. 10 children responded to the therapy demonstrated either by decrease of the solid tumor part or by decrease of catecholamines in urine or plasma or by decrease of bone-marrow involvement. One patient reached a complete remission continuing up to present time (longer than 180 days). 9 patients died meanwhile of tumor progression. 131J-MIBG is an effective instrument, to get a decrease of the tumor up to a complete remission in extensively pretreated patients with tumor relapse, which are refractory to chemotherapy.
3-Iodobenzylguanidine↗
Cerebral venous sinus thrombosis in children with acute lymphoblastic leukemia carrying the MTHFR TT677 genotype and further prothrombotic risk factors.
BACKGROUND: The present study was designed to prospectively evaluate the role of prothrombotic risk factors in leukemic children treated according to the ALL-BFM 90/95 study protocols with respect to the onset of cerebral venous sinus thrombosis. PATIENTS: 317 consecutive leukemic children aged 6 months to 18 years were enrolled in this study. 288 of the 317 patients were available for thrombosis-free survival analysis. RESULTS: In 17 (5.9%) of these 288 patients cerebral venous sinus thrombosis occurred. The overall event-free survival of thrombosis in the central nervous system in patients with at least one prothrombotic defect (n = 12) was significantly reduced compared with patients without a prothrombotic defect (p < 0.0001). 15 patients showed acute clinical symptoms at onset of cerebral venous sinus thrombosis, two were asymptomatic. Three of the 17 patients affected (17.6%) died directly associated with the thrombotic event during induction therapy, the remaining 14 patients did not show prolonged clinical symptoms. CONCLUSIONS: Prothrombotic risk factors should be included in a screening program in ALL children treated according to the BFM study protocols. Further prospective studies are recommended to establish adequate prophylactic anticoagulant treatment during ALL (BFM) polychemotherapy.
Adolescent↗
Central nervous system lymphoma in children.
This paper describes the rare MR and CT features of central nervous system (CNS) lymphoma in immunocompetent children and in survivors of childhood acute lymphoblastic leukemia (ALL) and discusses the causative role of cranial irradiation and/or leukoencephalopathy preceding central nervous system (CNS) lymphoma in survivors of childhood leukemia. The authors reviewed MR and CT scans of 3 children with biopsy-proved CNS lymphoma. One child had tumor infiltration within the optic nerve sheaths and optic chiasm by previously known non-Hodgkin lymphoma. In 2 patients, CNS lymphoma developed 8 and 10 years after initial ALL treatment. In both cases CNS lymphoma was preceded by cranial irradiation and leukoencephalopathy. A single lesion was present in 3 out of 4 patients. All lesions were isointense or hypointense on the T1-weighted images relative to gray matter and showed homogeneous enhancement. One lesion was centered in the central gray matter, one lesion was centered within a cerebral hemisphere, one lesion was in optic nerve, and there were 2 parasellar lesions. CNS lymphoma has a variable appearance in children. Knowledge of risk factors in children may help in the early recognition of disease, allowing for timely intervention. This may prompt early biopsy or a conservative management in the appropriate clinical setting.
Adolescent↗
Fatal haemoptysis associated with invasive pulmonary aspergillosis treated with high-dose amphotericin B and granulocyte-macrophage colony-stimulating factor (GM-CSF).
Opportunistic pulmonary infections are a leading cause of morbidity and mortality in patients with chemotherapeutically treated neoplasias. With increasingly aggressive cytotoxic regimens causing prolonged neutropenia, the risk of systemic mycoses and in particular of invasive pulmonary aspergillosis has increased. We review the case of a 10-year-old child suffering from relapsed lymphoblastic leukaemia and from high-dose amphotericin B-treated invasive pulmonary aspergillosis acquired during long-standing neutropenia in the initial phase of remission induction chemotherapy. The patient died in remission after GM-CSF-induced bone marrow recovery and clinical and radiological improvement with stable plasmatic coagulation and normal thrombocyte count. Peracute massive pulmonary bleeding caused by the simultaneous arrosion of a greater pulmonary artery and a lobar bronchus by a liquefactive fungal focus was responsible. In patients with chemotherapeutically induced neutropenia and invasive aspergillosis, bone marrow recovery may lead to the liquefaction of pulmonary foci, and, in view of the well-known vasotropic nature of the infection, to a potentially lethal arrosion bleeding. With the emerging use of colony-stimulating factors for shortening and overcoming neutropenia, this so far rare complication may become of increasing importance.
Amphotericin B↗