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  • 1
    Electronic Resource
    Electronic Resource
    Determination of the urinary excretion of ifosfamide and its phosphorated metabolites by phosphorus-31 nuclear magnetic resonance spectroscopy (1993)
    Springer
    Cancer chemotherapy and pharmacology 31 (1993), S. 387-394 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Phosphorus-31 nuclear magnetic resonance spectroscopy was used to analyze urine samples obtained from patients treated with ifosfamide (IF). This technique allows the individual assay of all phosphorated metabolites of IF in a single analysis without the need for prior extraction. In addition to the classic IF metabolites 2-dechloroethylifosfamide (2DECIIF), 3-dechloroethylifosfamide (3DECIIF), carboxyifosfamide (CARBOXYIF), and iso-phosphoramide mustard (IPM), several signals corresponding to unknown phosphorated compounds were observed. Four of them were identified: one is alcoifosfamide (ALCOIF), two come from the degradation of 2,3-didechloroethylifosfamide (2,3-DECIIF), and one results from the decomposition of 2DECIIF. The total cumulative drug excretion as measured over 24 h in nine patients was 51% of the injected IF dose; 18% of the dose was recovered as unchanged IF. The major urinary metabolites were the dechloroethylated compounds, with 3DECIIF excretion (11% of the injected dose) always being superior to 2DECIIF elimination (4% of the injected dose). Degradation compounds of 2DECIIF and 2,3DECIIF represented 0.4% of the injected dose. The metabolites of the dechloroethylation pathway always predominated over those of the activation pathway (CARBOXYIF, ALCOIF, and IPM, representing 3%, 0.8%, and 0.2% of the injected dose, respectively). In all, 14% of the injected dose was excreted as unknown phosphorated compounds. The interpatient variation in levels of IF metabolites was obvious and involved all of the metabolites. Renal excretion was not complete at 24 h, since 11% of the injected dose was recovered in the 24- to 48-h urine samples.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686153
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  • 2
    Electronic Resource
    Electronic Resource
    Phase I and pharmacology study of flavone acetic acid administered two or three times weekly without alkalinization (1994)
    Springer
    Cancer chemotherapy and pharmacology 35 (1994), S. 219-224 
    Details
    ISSN: 1432-0843
    Keywords: Key words Flavone acetic acid ; Phase I trial ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Flavone acetic acid (FAA, NSC 347512) is a synthetic flavonoid compound with a unique form of preclinical antitumor activity, but its mechanism of action is still not known. In an attempt to exploit the remarkable preclinical activity of this compound in such a way as to allow its use as a clinically useful agent, we performed a phase I and pharmacology study with frequent administration and no hyperhydration or alkalinization. Sixteen patients (9 men, 7 women) were given FAA as 6-h i.v. infusions 2 or 3 times a week (10 and 6 patients, respectively), at doses ranging from 2.5 to 8.1 g/m2. A total of 130 doses were administered during this study. Sedation, arterial hypotension, vomiting and diarrhea were the predominant toxicities observed at the highest dose (8.1 g/m2). One patient developed severe but reversible multiple organ failure. No treatment-related deaths occurred. Pharmacokinetics was linear for the doses studied, with peak plasma levels ranging from 39 to 449 μg/ml and a mean terminal half-life of 3.1 h. No drug accumulation was observed with this frequent-administration schedule. No objective response was observed. Three FAA infusions per week at 8.1 g/m2 could be recommended as an optimal and tolerable schedule.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686551
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  • 3
    Electronic Resource
    Electronic Resource
    Chronopharmacokinetics of doxorubicin in patients with breast cancer (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 287-291 
    Details
    ISSN: 1432-1041
    Keywords: Doxorubicin ; breast cancer ; chronopharmacokinetics ; total body clearance ; hepatic clearance ; hepatic blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The chronopharmacokinetics of doxorubicin (DOX) has been studied in 18 patients suffering from breast cancer. They received combined chemotherapy, including DOX (50 mg/m2 as an iv bolus), given at two different times (09.00 h or 21.00 h). The two randomized courses of the protocol were given to each patient at a four week interval. The total body clearance (CL) of DOX was significantly decreased when the drug was administered at 21.00 h, resulting in a longer elimination half-life and an increase in AUC. The renal clearance of DOX did not differ at the different times of administration, and it appears that the decrease in CL was related to a change in hepatic blood flow. The volume of distribution of the drug was not changed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315211
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  • 4
    Electronic Resource
    Electronic Resource
    Flucytosine conversion to fluorouracil in humans: Does a correlation with gut flora status exist? A report of two cases using fluorine-19 magnetic resonance spectroscopy (1991)
    Springer
    Infection 19 (1991), S. 178-180 
    Details
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei zwei Patienten fand sich eine Beziehung zwischen der Zusammensetzung der Darmflora, vor allem dem Anteil gramnegativer Stäbchenbakterien und derIn-vivo-Konversion von Flucytosin zu Fluorouracil, die während Behandlung mit der Kombination Flucytosin (6 bis 9 g pro Tag) plus Amphotericin B (1 mg/kg/Tag) durch Fluor-19 Magnet-Resonanz-Spektroskopie im Urin nachgewiesen wurde. Der Anteil des Fluorouracil-Metabolite war mit weniger als 0,6% der gesamten im Urin ausgeschiedenen fluorierten Verbindungen extrem niedrig solange die Koloniebildnerzahlen der Enterobazillen unter 103 lagen. Der prozentuale Anteil von Fluorouracil stieg auf 3,5 bis 8,8% an während sich die Enterobazillen erholten oder normalisierten und Koloniebildnerzahlen von 105 bis 108 erreichten. Die Kontrolle der Darmflora unter langfristiger Anwendung von Flucytosin ergibt möglicherweise hochinteressante Anhaltspunkte für eine Vorhersage des myelotoxischen Risikos durch den Metaboliten Fluorouracil.
    Notes: Summary A relationship between the gut flora level, particularly gram-negative enterobacilli, and thein vivo flucytosine conversion to fluorouracil has been observed in humans from the fluorine-19 magentic resonance spectroscopy analysis of urine from two patients treated with the flucytosine- (6 to 9 g/day) amphotericin B (1 mg/kg/day) combination. Indeed the percentage of fluorouracil metabolites was extremely low (〈0.6% of total fluorinated compounds excreted) when the number of enterobacillary colonies was low (〈103) and higher (3.5 to 8.8%) when enterobacillary colonies were under reconstitution or in the normal range (105 to 108). The intestinal microflora assessment may therefore be of high interest to predict the risk of an additive flucytosine-induced myelotoxicity suspected to be due to fluorouracil during flucytosine chronic therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01643246
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  • 5
    Electronic Resource
    Electronic Resource
    Dumbbell-shaped spinal epidural cavernous angioma. Case report (1994)
    Springer
    Neurological sciences 15 (1994), S. 429-432 
    Details
    ISSN: 1590-3478
    Keywords: spinal cord tumor ; epidural cavernous angioma ; dumbbell-shaped tumor ; vascular malformation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Sommario L'angioma cavernoso è una lesione frequente nel sistema nervoso centrale. Esso è caratterizzato da un insieme di vasi dilatati rivestiti da un sottile endotelio e non separati da tessuto nervoso normale. Gli angiomi cavernosi si ritrovano più frequentemente a livello encefalico. A livello spinale la localizzazione più comune è quella intravertebrale. Gli angiomi cavernosi intradurali extramidollari e quelli intramidollari sono meno frequenti, mentre la localizzazione extradurale è rara. Gli angiomi cavernosi spinali extradurali “a clessidra” sono molto rari. Per quanto ne sappiamo, ne sono stati riportati solo 6 casi in letteratura. Descriviamo un caso giunto alla nostra osservazione con un quadro RMN che, seppure in accordo con tale tipo di lesione, non permetteva una diagnosi differenziale con il neurinoma, che è una patologia molto più comune. L'exeresi chirurgica rappresenta il trattamento di scelta degli angiomi cavernosi. È necessario comunque uno studio radiologico completo per escludere concomitanti localizzazioni a livello di altri organi.
    Notes: Abstract Cavernous angiomas are common lesions of the CNS characterized by abnormally dilated blood vessels lined by a thin endothelium, closely clustered together and not separated by normal neural tissue. They are more frequently found intracranially. In the spine, a common location is the vertebral bodies. Intradural extramedullary and intramedullary cavernous angiomas are less frequent lesions, while purely epidural locations are uncommon. Spinal dumbbell-shaped epidural cavernous angiomas are exceedingly rare, and only six cases have been reported in the literature. We describe one additional case whose MRI appearance was indistinguishable from that of a neurinoma, which is a much more common lesion. Surgical treatment is advised and complete radiological evaluation is necessary to rule out concomitant localizations in other organs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02339907
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  • 6
    Electronic Resource
    Electronic Resource
    Askin's tumor in children: report of two cases (1992)
    Springer
    Pediatric surgery international 7 (1992), S. 73-75 
    Details
    ISSN: 1437-9813
    Keywords: Askin's tumor ; Peripheral neuroectodermal tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two cases of Askin's tumor of the thoracopulmonary region in children (a 6-year-old female and a 5-year-old male) are presented. Primary surgery was unfeasible and despite aggressive chemotherapy both died within 304 and 300 days, respectively, from the onset of the disease. Although rare, Askin's tumor should be considered in the differential diagnosis of any thoracopulmonary mass in childhood and adolescence through appropriate histology and immunohistochemistry of incisional biopsies. Its prognosis is poor unless radical surgery is performed as soon as possible: unresectable tumors can be treated with chemotherapy, but prolonged chemotherapy yields potentially lethal complications. We conclude that only early diagnosis and cytogenetic recognition can give children with Askin's tumor a chance of curative surgery.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00181010
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