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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of dermatology 30 (1991), S. 0 
    ISSN: 1365-4632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The term cutaneous T-cell lymphoma (CTCL) encompasses the spectrum of diseases characterized by a monoclonal proliferation of malignant T lymphocytes predominantly of the mature T-helper cell type. These include mycosis fungoides, which is usually localized to the skin for many years, and the Sezary syndrome, the leukemic variant in which characteristic, bizzare lymphatic cells with deeply indented or cerebriform nuclei, the Sezary cells, infiltrate lymph glands and internal organs such as the spleen, liver, lungs, heart, and bone marrow. The condition is more common in men after their fourth decade. The treatment of CTCL varies depending on the stage of the disease. The skin of the patient is the primary index of effectiveness of therapy. Options range from topical steroids, topical nitrogen mustard, X-irradiation, electron beam irradiation, and 8–methoxypsoralen (8–MOP) combined with ultraviolet A photochemotherapy (PUVA), to leukapheresis and systemic chemotherapy. More recently, extracorporeal photochemotherapy (ECPC) has been introduced. The safety and efficacy of this modality is further investigated in six patients who fullfilled the criteria of diagnosis of CTCL. The problems encountered in objectively evaluating the clincal responses in the patients are outlined and improvements in the protocol to overcome these are suggested. The proposed mechanism of action is an immunostimulatory one and a procedure that is relatively free from side effects; it offers promise as a potential treatment for a difficult cancer.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 732 (1994), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
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    State College, Miss. : Periodicals Archive Online (PAO)
    Mississippi Quarterly. 45:1 (1992) 118 
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  • 4
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Our evidence comes from comparison of the concentrations of high-affinity, saturable binding sites for oestradiol and anti-oestrogens in the same cytosol preparations, and from competition experiments with tritiated anti-oestrogens. Typical results of saturation analysis experiments with ...
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0843
    Keywords: Key words MX2  ;  Pharmacokinetics  ;   Pharmacodynamics  ;  Anthracyclines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the present study was to investigate the pharmacokinetics and pharmacodynamics of the new morpholino anthracycline drug MX2. A total of 27 patients with advanced cancer participated in a dose-escalation study in the first cycle of treatment with drug given i.v. at doses of 10–50 mg/m2 (total dose 16.8–107.5 mg). The mean total systemic plasma clearance (CL) of MX2 was 2.98 ± 1.68 l/min, the mean volume of distribution at steady state was 1460 ± 749 l and mean elimination half-life was 10.8 ± 5.1 h. The area under the plasma concentration-time curve (AUC) of MX2 was linearly related to the dose per kilogram and the dose per body surface area (r 2 = 0.43, P 〈 0.01 and r 2 = 0.44, P 〈 0.01, respectively). CL did not correlate with total body weight, lean body mass or body surface area. The mean elimination half-lives of the metabolites M1, M2, M3 and M4 were 11.8 ± 5.0, 21.9 ± 11.8, 19.0 ± 11.3 and 12.3 ± 6.3 h, respectively. The fractional E max model produced a much better fit to the relative nadir neutrophil count versus dose data (r 2 = 0.42) than to the relative nadir neutrophil count versus AUC or peak concentration (C max) data (r 2 = 0.15 and 0.09, respectively). There seemed to be a threshold dose of about 65 mg of MX2 at or above which a large proportion of patients had a nadir neutrophil count of less than 0.5 × 109/l. This study shows that the pharmacokinetics of MX2 are similar to those of other anthracyclines. With other anthracyclines the degree of myelosuppression seems to depend more on the AUC and C max than on the delivered dose; however, with MX2 the degree of myelosuppression depends more on the dose given than on drug exposure expressed as the AUC or C max.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In all, 18 patients with histologically proven advanced cancer received 400 mg/m2 carboplatin (CBDCA) plus 800 mg/m2 cyclophosphamide (level 1), and 14 others received 550 mg/m2 CBDCA plus 1100 mg/m2 cyclophosphamide (level 2). A maximum of six cycles was given if a response occurred. The dose-limiting toxicity was myelosuppression, with neutropenia being more marked than thrombocytopenia. At level 2, patients experiencing a fibrile-neutropenic event showed a mean 24-h urinary creatinine clearance value of 1.1 ml/s (95% confidence limits 0.8–1.4 ml/s), whereas in those who remained afebrile it was 1.7 ml/s (95% confidence limits, 1.3–2.0 ml/s). This difference was significant (P〈0.01). Other toxicities were only mild. Creatinine clearance is a predictor of febrile episodes after treatment with high doses of CBDCA and cyclophosphamide. We are now conducting a study using human granulocyte colony-stimulating factor to reduce the incidence of neutropenia with escalating doses of these drugs in an attempt to prevent febrile events.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0843
    Keywords: Key words MX2 ; Pharmacokinetics ; Filgrastim G-CSF ; Myelosuppression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To investigate the effect of granulocyte colony-stimulating factor (G-CSF) on the pharmacokinetics and pharmacodynamics of the new morpholino anthracycline drug MX2. Methods: A total of 25 patients with advanced malignant disease participated in a dose-escalation study in the first cycle of treatment given i.v. at doses of 50–80 mg/m2 (74–152 mg) with concomitant filgrastim (G-CSF, 5 μg/kg) given daily beginning at 24 h after the dose of MX2. Results: The mean fast distribution half-life (1.5 ± 1.0 min) and the mean plasma clearance (2.18 ± 0.95 l/min) were significantly lower than the respective mean values found in a previous study in which 27 patients had received MX2 (16.8–107.5 mg) alone (3.3 ± 2.2 min and 2.98 ± 1.68 l/min, respectively; P 〈 0.05). There was no correlation between plasma clearance and the delivered dose for the combined MX2-alone and MX2-filgrastim groups, indicating that the lower clearance observed in the G-CSF group was probably not due to the higher dose. Elimination half-lives of the metabolites M1 and M4 were significantly greater in the filgrastim group (19.8 ± 14.7 and 11.8 ± 5.0 h for M1 and 14.8 ± 4.1 and 12.3 ± 6.3 h for M2, respectively). Unlike the MX2-alone group, there was no relationship in the MX2- filgrastim group between the relative nadir neutrophil count and the dose or between the duration of grade IV neutropenia and the dose of MX2. Conclusions: This study shows that filgrastim decreased the plasma clearance of MX2 by approximately 25%, possibly by inhibition of metabolism.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Carboplatin was given as a 30-min infusion to 11 ovarian cancer patients at doses of 170–500 mg/m2. The ages, weights, and creatinine clearances (Clcr) ranged from 44 to 75 years, from 44 to 74 kg, and from 32 to 101 ml/min, respectively. Plasma, plasma ultrafiltrate (PU), and urine samples were obtained at appropriate times for 96 h and were analyzed for platinum. The PU and urine were also analyzed for the parent compound by HPLC. In patients with a Clcr of about 60 ml/min or greater, carboplatin decayed biexponentially with a mean t1/2α of 1.6 h and a t1/2β of 3.0 h. The mean (±SD) residence time, total body clearance, and apparent volume of distribution were 3.5±0.4 h, 4.4±0.85 l/h, and 16±31l, respectively. Cmax and AUCinf values increased linearly with dose, and the latter values correlated better with the dose in mg than in mg/m2. No significant quantities of free, ultrafilterable, platinum-containing species other than the parent compound were found in plasma, but platinum from carboplatin became protein-bound and was slowly eliminated with a minimal t1/2 of 5 days. The major route of elimination was excretion via the kidneys. Patients with a Clcr of 60 ml/min or greater excreted 70% of the dose as the parent compound in the urine, with most of this occurring within 12–16 h. All of the platinum in 24-h urine was carboplatin, and only 2%–3% of the dosed platinum was excreted from 48 to 96 h. Patients with a Clcr of less than about 60 ml/min exhibited dose-disproportional increases in AUCinf and MRT values. The latter were inversely related to Clcr (r=-0.98). Over a dose range of 300–500 mg/m2, carboplatin exhibited linear, dose-independent pharmaco-kinetics in patients with a Clcr of about 60 ml/min or greater, but dose reductions are necessary for patients with mild renal failure.
    Type of Medium: Electronic Resource
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  • 9
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    New Brunswick, N.J. : Periodicals Archive Online (PAO)
    Journal of American Ethnic History. 2:1 (1982:Fall) 107 
    ISSN: 0278-5927
    Topics: English, American Studies , Ethnic Sciences , History
    Notes: Reviews
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 42 (1999), S. 403-418 
    ISSN: 1530-0358
    Keywords: Rectal cancer ; Adjuvant therapy ; Radiotherapy ; Chemotherapy ; Pelvic floor function ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Although adjuvant chemoradiotherapy may improve outcomes after surgery for high-risk rectal cancer, its toxicities are not well documented. This is a review of complications associated with adjuvant therapy in randomized, controlled trials. METHODS: A MEDLINE and literature search was performed for randomized, controlled trials of adjuvant therapy for rectal cancer. Modalities of adjuvant therapy evaluated included preoperative radiotherapy, preoperative chemoradiotherapy, postoperative radiotherapy, and postoperative chemoradiotherapy. All documented complications were analyzed, including any effect on pelvic floor function and quality of life. RESULTS: Short-term (acute) complications of preoperative radiotherapy include lethargy, nausea, diarrhea, and skin erythema or desquamation. These acute effects develop to some degree in most patients during treatment but are usually self-limiting. With preoperative radiotherapy the incidence of perineal wound infection increases from 10 to 20 percent. The acute toxicities after postoperative radiotherapy for rectal cancer occur in 4 to 48 percent of cases, and serious toxicities, requiring hospitalization or surgical intervention, occur in 3 to 10 percent of cases. Postoperative radiotherapy is associated with more complications than preoperative radiotherapy. The main problems with postoperative radiotherapy are small-bowel obstruction (5–10 percent), delay in starting radiotherapy caused by delayed wound healing (6 percent) and postoperative fatigue (14 percent), and toxicities precluding completion of adjuvant therapy (49–97 percent). The morbidity and mortality of both preoperative and postoperative radiotherapy are higher in elderly patients and when two-portal rather than three-portal or four-portal radiation technique is used. Meticulous radiation technique is important, and multiple fields of irradiation are mandatory. After combined adjuvant chemotherapy and radiotherapy acute hematologic and gastrointestinal toxic effects are frequent (5–50 percent). Delayed radiation toxicities include radiation enteritis (4 percent), small-bowel obstruction (5 percent), and rectal stricture (5 percent). Pelvic floor function and quality of life have not been well evaluated in randomized, controlled trials. CONCLUSION: Adjuvant therapy for rectal cancer has considerable adverse effects. Adverse effects on bowel and sphincter function and quality of life have not been defined.
    Type of Medium: Electronic Resource
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