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  • 1
    ISSN: 1432-1440
    Keywords: Digitoxin poisoning ; Immunoassay ; Digitalis antibody Fab-fragment therapy ; Serum ; Urine ; Dialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 36 year old male was admitted to the intensive care unit with acute digitalis intoxication after ingestion of 350 digitoxin tablets (=35 mg digitoxin). He was treated with Fab fragments of a digitalis antiserum raised in sheep, the concentrations of digitoxin in serum, urine and dialysates being measured with two automated digitoxin immunoassays based on fluorescence labelling techniques. Whereas one assay reflected the total digitoxin concentrations, including that bound to the antidote, the other measured only the bioactive “free” form of the drug. This article examines the use and limitations of both assay systems in assessing and monitoring cases of digitalis poisoning.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0843
    Keywords: Key words Fractionated ifosfamide therapy ; Urinary ifosfamide metabolites ; Urinary mesna excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The oxazaphosphorine antineoplastic ifosfamide (IF) is metabolized by two different initial pathways: ring oxidation (“activation”), forming 4-OH-IF (“activated IF”), and side-chain oxidation with liberation of chloroacetaldehyde (CAA), forming the inactive metabolites 3-dechloroethylifosfamide or 2-dechloroethylifosfamide (3-DCE-IF, 2-DCE-IF). 4-OH-IF and 4-OH-IF-derived acrolein are thought to be responsible for IF-induced urotoxicity (hemorrhagic cystitis), whereas CAA may be involved in IF-associated nephrotoxicity (renal tubular damage). The thiol compound 2-mercaptoethane sulfonate sodium (mesna) has proved to inactivate sufficiently the urotoxic metabolites of oxazaphosphorine cytostatics and is therefore routinely given to patients receiving IF chemotherapy. The cumulative urinary excretion of IF, 4-OH-IF, 3-DCE-IF, 2-DCE-IF, mesna, and its disulfide dimesna was studied in 11 patients with bronchogenic carcinoma receiving IF on a 5-day divided-dose schedule (1.5 g/m2 daily) with concomitant application of mesna (0.3 g/m2 at 0, 4, and 8 h after IF infusion). On day 1 the mean cumulative 24-h urinary recoveries (percentage of the IF dose) recorded for IF, 4-OH-IF, 3-DCE-IF, and 2-DCE-IF were 13.9%, 0.52%, 4.8%, and 1.5%, respectively. On day 5 the corresponding values were 12.2%, 0.74%, 9.9%, and 3.6%, respectively. This time-dependent increase in urinary excretion of IF metabolites, which is caused by rapid autoinduction of hepatic oxidative metabolism, may result in a higher probability for the development of urotoxic and nephrotoxic side effects during prolonged IF application. The mean 24-h urinary recoveries (percentage of the daily mesna dose) recorded for mesna/dimesna on day 1 (day 5) were 23.8%/45.2% (21.2%/39.8%), respectively. The mean molar excess of urinary reduced (“free”) mesna over 4-OH-IF ranged from 11 to 72 on day 1 and from 6 to 40 on day 5. This indicates that although urinary excretion of 4-OH-IF rises with repeated IF application, mesna in standard doses should sufficiently inactivate the urotoxic IF metabolites.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1238
    Keywords: Sepsis ; Hemolysis ; Clostridium perfringens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 61-year-old man developed a pyrescia accompanied by a massive intravascular hemolysis after abdominal surgery (Whipple's operation) of a pancreatic adenocarcinoma. Abdominal ultrasound and the abdominal CT-scan showed marked aerobilia and multiple liver abscesses. Laboratory tests demonstrated the presence of the Thomsen-Friedenreich cryptantigen (TCA) on the membranes of the patient's erythrocytes. The enzymatic cleavage of N-acetyl-neuraminic acid usually covering the TCA may lead to a life threatening intravascular hemolysis. Since Clostridial bacteriae typically synthesize neuraminidase, the presumptive diagnosis of Clostridial sepsis complicated by massive hemolysis was made. Immediate antibiotic therapy including penicillin G and metronidazole stopped hemolysis within a few hours and the patient servived. On the following day, microbiological examination identifiedClostridium perfringens in the patient's blood cultures. Clostrial sepsis should be suspected in patients with underlying infections and/or malignant diseases, particularly of the gastrointestinal or genitourinary tract, who present with septic shock and acute intravascular hemolysis. Whereas microbiological specification of the organism is time consuming, the relatively simple agglutination test with anti-TCA peanut lectin can provide a rapid presumptive diagnosis. The immediate onset of an appropriate antimicrobial therapy is of central importance and might be life-saving.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Intensive care medicine 18 (1992), S. 439-442 
    ISSN: 1432-1238
    Keywords: Digitoxin ; Intoxication ; Antibody fragments ; Fab treatment ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A massive digitoxin (DGTX) intoxication in a 36-year-old man (35 mg DGTX) was treated by prolonged and repeated i.v.-infusions of Fab fragments of anti-digitalis antibodies (FAB). Blood and urine samples were collected over a 98 h period for monitoring the efficacy and adequacy of FAB treatment. DGTX concentrations were determined after protein precipitation (release of FAB-bound and protein-bound DGTX) in unprocessed serum and urine samples, and after aliquots of these samples had been dialysed in vitro against DGTX-free buffer (elimination of DGTX not bound to FAB). The difference in DGTX concentration between the unprocessed and dialysed samples was the amount of DGTX bound to plasma proteins and the small fraction of unbound DGTX being relevant for the therapeutic and toxic effects of the drug. Before FAB therapy was started, the total serum DGTX concentration was 535 nmol/l. The first FAB infusion (320 mg) was started 11 h after drug ingestion. Since this amount of FAB was insufficient to bind all DGTX present in the serum, cardiac DGTX toxicity (total AV-block) persisted. During a second FAB infusion (400 mg) the patient reverted to regular AV-conduction. At this time most of the DGTX in serum was FAB-bound. Toxic symptoms (sinus arrest) reappeared twice and were accompanied by increasing amounts of non-antibody-bound DGTX in the serum. Additional application of FAB (2×80 mg) resulted in the immediate disappearance of arrhythmia. During FAB-treatment total DGTX serum concentrations and renal DGTX clearance rose, indicating redistribution of drug from tissue to serum and urinary elimination of FAB-bound DGTX, respectively. At 98 h after onset of therapy the DGTX serum level was within the therapeutic range. This case confirms that cardiac toxicity of DGTX can be successfully treated with FAB antidote. The amount of FAB given as a loading dose must be sufficient to bind all DGTX present in the serum and FAB infusions have to be continued over several hours to inactivate DGTX as it leaves the tissue compartment during redistribution.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 117 (1991), S. S148 
    ISSN: 1432-1335
    Keywords: Ifosfamide ; Activated ifosfamide ; Chloroacetaldehyde ; Metabolism ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The initial metabolism of ifosfamide (IF) consists of two different pathways: enzymatic hydroxylation at carbon-4 forms the cytostatically active metabolite 4-OH-IF (“activated ifosfamide”) whereas side-chain oxidation results in the liberation of chloroacetaldehyde, a compound with possible neurotoxic properties. The pharmacokinetics of ifosfamide and its activated form were investigated in 12 cancer patients, who received both oral and i.v. treatment in a randomized sequence on days 1 and 3 at a dose of 1 g/m2 (n=7) or 1.5 g/m2 (n=5). In 3 patients the pharmacokinetics of chloroacetaldehyde were also investigated. After oral application, ifosfamide absorption proceeded rapidly, the oral bioavailability was 0.92. Independent of the route of ifosfamide application on day 1, the terminal half-life on day 3 (when the drug was given by the alternative route) was decreased in 6 out of the 12 patients, thus indicating self-induction of hepatic metabolism. 4-OH-IF was already present 20 min after ifosfamide administration. In the individual patient the concentrations of 4-OH-IF were always higher after oral than after i.v. IF application: the mean p.o.:i.v. ratios forc max and the area under the concentration/time curve were 2.3 and 1.7 respectively (P〈0.05). In a first series of 3 patients the chloroacetaldehyde concentrations measured after oral ifosfamide application were about twice as high as those when the drug was given intravenously. These results indicate that (in comparison to the i.v. route) orally administered ifosfamide may be more cancerotoxic but also leads to higher levels of chloroacetaldehyde. This would explain the neurotoxic sideeffects previously seen after oral administration of comparatively low ifosfamide doses.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1435-1285
    Keywords: Schlüsselwörter Instabile Angina – Myokardinfarkt – Prädiktoren – Quantitative Koronarangiographie – Restenose ; Key words Myocardial infarction – predictors – quantitative coronary¶angiography – restenosis –¶unstable angina
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Angioplasty in acute coronary syndromes is complicated by a high rate of early vessel reocclusion and restenosis. Therefore, it is recommended to achieve a „stent-like” result by percutaneous transluminal coronary angioplasty (PTCA) or otherwise use coronary stenting (provisional stenting).¶   This study sought to determine angiographic and patient-related factors that are associated with early target vessel reocclusion or luminal renarrowing after coronary intervention in acute coronary syndromes (ACS).¶   In an observational prospective study we investigated 161 patients with ACS (acute myocardial infarction and unstable angina) submitted to PTCA. In 140 patients a follow-up angiography after 10 days was obtained. All angiograms were quantitatively evaluated by computerized measurements.¶   Target vessel reocclusion and early luminal renarrowing was observed in 10 patients (7.1%) and 19 patients (13.6%), respectively. Using univariate analysis, significant risk factors (P 〈0.05) for early reocclusion and renarrowing were diabetes mellitus (relative risk [RR] 6.1 and 5.0), arterial hypertension (RR 7.7 and 3.3), postprocedural lesion length ≥2.5mm (RR 6.8 and 7.1), postprocedural minimal lumen diameter ≤2.5 mm (RR9.0 and 5.8), residual stenosis ≥25% (RR 4.8 and 3.5) and absence of stents (RR 4.1 and 3.2). Moreover, in multivariate analysis hypertension and postprocedural lesion length could be identified as independent risk factors for reocclusion and renarrowing. Diabetes mellitus was found to be an independent risk factor for renarrowing.¶   Conclusions: In a consecutive series of patients with ACS undergoing PTCA with provisional stenting the occurrence of early target vessel reocclusion and luminal renarrowing is lower than previously reported for this subset of patients treated by PTCA alone. Adverse outcome is related to absence of stents, angiographic factors (residual stenosis, lesion length, minimal lumen diameter after procedure) and patient-related factors such as diabetes and hypertension.
    Notes: Zusammenfassung Die Angioplastie beim akuten Koronarsyndrom wird durch eine hohe Rate früher Gefäß-Reokklusionen und Restenosen kompliziert. Daher wird bei der perkutanen transluminalen Koronarangioplastie (PTCA) im klinischen Alltag oft ein „stent-gleiches“ Ergebnis angestrebt und andernfalls eine intrakoronare Stentimplantation durchgeführt (provisional stenting).¶   Diese Studie sollte angiographische und patientenbezogene Risikofaktoren aufzeigen, die für Frühverschluss oder Lumeneinengung des Zielgefäßes nach Koronarintervention bei akutem Koronarsyndrom (AKS) prädisponieren.¶   In einer prospektiven Verlaufsbeobachtung untersuchten wir 161 Patienten mit AKS (akuter Myokardinfarkt und instabile Angina pectoris), die mittels PTCA behandelt wurden. Bei 140 Patienten konnte eine Verlaufsangiographie nach 10 Tagen durchgeführt werden. Alle Angiogramme wurden quantitativ durch computerunterstützte Auswertung analysiert.¶   Reokklusion und Lumeneinengung des Zielgefäßes traten bei 10 Patienten (7,1%) bzw. 19 Patienten auf (13,6%). Als signifikante Risikofaktoren (p 〈0,05) für Frühverschluss und Lumeneinengung zeigten sich in der univariaten Analyse Diabetes mellitus (relatives Risiko [RR] 6,1 und 5,0), arterieller Hypertonus (RR 7,7 und 3,3), postinterventionelle Läsionslänge ≥2,5 mm (RR 6,8 und 7,1), postinterventioneller minimaler Lumendiameter ≤2,5 mm (RR 9,0 und 5,8), Reststenose ≥25% (RR 4,8 und 3,5) und das Fehlen eines Stents (RR 4,1 und 3,2). Außerdem konnten in der multivariaten Analyse Hypertonus und postinterventionelle Läsionslänge als unabhängige Risikofaktoren für Reokklusion und Lumeneinengung identifiziert werden. Zusätzlich fand sich Diabetes mellitus als unabhängiger Risikofaktor für eine Lumeneinengung.¶   Schlussfolgerungen: In einer Verlaufsserie von Patienten mit AKS, die mittels PTCA und provisional stenting behandelt wurden, ist die Inzidenz für Frühverschluss und Lumeneinengung des Zielgefäßes niedriger als bisher für dieses Patientenkollektiv bei alleiniger PTCA beschrieben. Die genannten Komplikationen sind verknüpft mit dem Fehlen eines Stents, angiographischen Faktoren (Reststenose, postinterventionelle Läsionslänge und minimaler Lumendiameter) und patientenbezogenen Faktoren wie Diabetes oder Hypertonus.
    Type of Medium: Electronic Resource
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