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  • Brain resuscitation  (2)
  • Childhood tumor  (2)
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Cancer immunology immunotherapy 41 (1995), S. 331-338 
    ISSN: 1432-0851
    Schlagwort(e): Chimeric antibody ; Elimination ; Kinetics ; Half-life ; Childhood tumor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A comprehensive analysis of the pharmacokinetics of human-mouse chimeric anti-ganglioside GD2 antibody mAb ch 14.18 was performed during a phase I clinical trial of ten children with neuroblastoma and one adult with osteosarcoma. The patients received a total of 20 courses of ch 14.18 at dose levels from 10 mg/m2 to 200 mg/m2. The plasma clearance of ch 14.18 was biphasic. Following the first course of treatmentt1/2,α was 3.4±3.1 h andt1/2,β 66.6±27.4 h in 9/10 children. Thet1/2,β values were significantly less than those of 181±73 h previously reported in adult melanoma patients (P〈-0.001), and 147.5 h in the adult osteosarcoma patient in our trial. The latter suggests different pharmacokinetics of mAb ch 14.18 in children and adults. After a second course of treatment, administered to 5/10 children,t1/2,β decreased significantly from 72.9±19.8 h to 31.7±18.4 h (P=0.015). We there-fore conclude that the elimination kinetics of mAbs ch 14.18 in children and adults are different, and furthermore that repeated administration of mAb ch 14.18 to children with neuroblastoma leads to accelerated antibody clearance.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Cancer immunology immunotherapy 41 (1996), S. 331-338 
    ISSN: 1432-0851
    Schlagwort(e): Key words Chimeric antibody ; Elimination ; Kinetics ; Half-life ; Childhood tumor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  A comprehensive analysis of the pharmacokinetics of human-mouse chimeric anti-ganglioside GD2 antibody mAb ch14.18 was performed during a phase I clinical trial of ten children with neuroblastoma and one adult with osteosarcoma. The patients received a total of 20 courses of ch14.18 at dose levels from 10 mg/m2 to 200 mg/m2. The plasma clearance of ch14.18 was biphasic. Following the first course of treatment t 1/2, α was 3.4±3.1 h and t 1/2, β 66.6±27.4 h in 9/10 children. The t 1/2, β values were significantly less than those of 181±73 h previously reported in adult melanoma patients (P≤ 0.001), and 147.5 h in the adult osteosarcoma patient in our trial. The latter suggests different pharmacokinetics of mAb ch14.18 in children and adults. After a second course of treatment, administered to 5/10 children, t1/2, β decreased significantly from 72.9±19.8 h to 31.7±18.4 h (P = 0.015). We therefore conclude that the elimination kinetics of mAbs ch14.18 in children and adults are different, and furthermore that repeated administration of mAb ch14.18 to children with neuroblastoma leads to accelerated antibody clearance.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-1238
    Schlagwort(e): Brain resuscitation ; Cardiac arrest ; Cerebral ischemia ; Microcirculation ; Thrombolytic therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Objective Successful resuscitation of the brain requires complete microcirculatory reperfusion, which, however, may be impaired by activation of blood coagulation after cardiac arrest. The study addresses the question of whether postischemic thrombolysis is effective in reducing cerebral noreflow phenomenon. Design 14 adult normothermic cats were submitted to 15-min cardiac arrest, followed by cardiopulmonary resuscitation (CPR) and 30 min of spontaneous recirculation. The CPR protocol included closed-chest cardiac massage, administration of epinephrine 0.2 mg/kg, bicarbonate 2mEq/kg per 30 min, and electrical defibrillation shocks. Interventions During CPR, animals in the treatment group (n=6) received intravenous bolus injections of 100 U/kg heparin and 1 mg/kg recombinant tissue type plasminogen activator (rt-PA), followed by an infusion of rt-PA 1mg/kg per 30 min. Measurements and results Microcirculatory reperfusion of the brain was visualized by labeling the circulating blood with 300 mg/kg of 15% fluorescein isothiocyanate albumin at the end of the recirculation period. Areas of cerebral noreflow — defined as the absence of microvascular filling — were identified by fluorescence microscopy at eight standard coronal levels of forebrain, and expressed as the percentage of total sectional area. One animal in the treatment group was excluded from further analysis because of intracerebral hemorrhage due to brain injury during trepanation. Autopsy revealed the absence of intracranial, intrathoracic, or intra-abdominal bleeding in all the other animals. In untreated animals (n=8), no-reflow affected 28±13% of total forebrain sectional areas, and only 1 out of 8 animals showed homogeneous reperfusion (i.e., no-reflow 〈15% of total forebrain sectional areas). Thrombolytic therapy (n=5) significantly reduced no-reflow to 7±5% of total forebrain sectional areas and all treated animals showed homogeneous reperfusion at the microcirculatory level. Conclusions The present data demonstrate that thrombolytic therapy improves microcirculatory reperfusion of the cat brain when administered during reperfusion after cardiac arrest.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Intensive care medicine 21 (1995), S. 132-141 
    ISSN: 1432-1238
    Schlagwort(e): Brain resuscitation ; Cardiac arrest ; Cerebral ischemia ; Closed chest cardiac massage ; Microcirculation ; No-reflow
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Objective Successful resuscitation of the brain requires unimpaired blood recirculation. The study addresses the question of the severity and reversibility of no-reflow after cardiac arrest. Design Adult normothermic cats were submitted to 5, 15 and 30 min cardiac arrest by ventricular fibrillation. The extent of no-reflow was assessed in each cardiac arrest group after 5 min closed chest cardiac massage in combination with 0.2 mg/kg epinephrine or after successful resuscitation followed by 30 min recirculation. Measurements and results Reperfusion of the brain was visualized by labelling the circulating blood with FITC-Albumin. Areas of no-reflow, defined as absence of microvascular filling, were identified by fluorescence microscopy at 8 standard coronal levels of forebrain, and expressed as percent of total sectional area. During cardiac massage, noreflow affected 21±5%, 42±38% and 70±27% of forebrain after 5, 15 and 30 min cardiac arrest, respectively. After 30 min spontaneous recirculation following successful resuscitation of the heart, no-reflow significantly declined to 7±11% after 5 min cardiac arrest (p〈0.05) but persisted in 30±11% and 65±21% of forebrain after 15 and 30 min cardiac arrest, respectively (n.s.). Conclusion Our observations demonstrate that resuscitation of the heart by closed chest massage causes severe (and after prolonged cardiac arrest irreversible) no-reflow of the brain. This suggests that no-reflow is an important cause of postresuscitation brain pathology.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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