Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukopenia or pancytopenia as a result of bone marrow dysfunction are manifestations of various diseases or complications of therapeutic regimens. The spectrum of diseases associated with leukopenia is wide and includes congenital as well as acquired neutropenias secondary to conditions such as myelodysplastic syndromes, AIDS, malignant tumors with or without chemotherapy-enhanced neutropenia, bone marrow transplantation or therapeutic or accidental radiation. The morbidity and mortality of infectious diseases is greatly enhanced during neutropenic phases. Over the last few years attempts have been made to shorten the duration and lessen the severity of neutropenia in patients with the above conditions by administration of Granulocyte Macrophage Colony Stimulating Factor (G-CSF). Both cytokines were successfully tested in phase I and II trials. Treatment with GM-CSF or G-CSF results in a dose-dependent increase of the neutrophil count. GM-CSF also increases the number of eosinophils and monocytes in peripheral blood. The effect of both cytokines on the neutrophil count is transient as long as the underlying disease persists. This prompted the institution of maintenance therapy, which has been successfully used with either cytokine. Long-term treatment is usually well tolerated and results in a reduction in the frequency of infections as well as in the duration of antibiotic treatments. Side effects of GM-CSF or G-CSF are usually mild and include fever, myalgia, bone pain, and erythema. A number of patients developed dyspnea, hypotension, sweating, flushing and erythema after the first dose of GM-CSF in each treatment cycle. This first-dose reaction occurs more frequently after intravenous than reactions were reported with G-CSF. Some patients with myelodysplastic syndrome progressed to acute myeloic leukemia during or after treatment with GM-CSF or G-CSF. Most of these patients presented with an increased fraction of blasts in the bone marrow, which preceded the treatment with the colony stimulating factors. Since GM-CSF and possibly G-CSF may increase the risk of developing acute leukemia in patients with myelodysplastic syndrome, it appears prudent to limit the use of these cytokines in patients with this disease. The subcutaneous route of administration appears to be preferable to intravenous administration, since the incidence and severity of side effects are reduced. While many questions concerning dosage, long-term therapy and combination therapy still remain unanswered, the information presented in this review concerning the clinical use of these cytokines warrants an optimistic outlook.
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PMID:[GM-CSF and G-CSF: cytokines in clinical application]. 170 94

After Phase I studies of benzisoquinolinedione (amonafide) in solid tumors identified myelosuppression as the dose-limiting toxicity, we conducted a Phase I study in patients with relapsed or refractory acute leukemia to define the optimal dose. Amonafide was given i.v. over 2-4 h daily for 5 days. The starting dose was 600 mg/m2/day with subsequent escalation to 750, 900, 1100, 1400, and 1800 mg/m2/day. Thirty-eight courses were administered to 24 patients, of whom 12 participated in concomitant pharmacological studies. Nausea and vomiting, transient orange discoloration of the skin, and tinnitus occurred at all dose levels. The latter symptom, along with lightheadedness and flushing, was related to infusion duration; this was increased to 4 h with doses greater than or equal to 900 mg/m2. The dose-limiting toxicities were mucositis and painful skin erythema which occurred in all 4 patients treated with 1800 mg/m2. No remissions occurred. Clearing of peripheral blood blasts occurred in 67% of patients treated with 1100 mg/m2 and in all patients treated with greater than or equal to 1100 mg/m2/day. A decrease in marrow leukemic infiltrate (% blasts x % cellularity) to less than 10% occurred in 15 and 50% of patients treated at these levels, respectively. There were 10 deaths (42%), which were unrelated to dosage. The harmonic mean terminal plasma half-life was 4.6 h (range, 2.5-35.5 h). Three patients had long drug half-lives of 9.7, 16.4, and 35.5 h and each had initial bilirubin levels greater than 1.0 mg/dl. The average urinary excretion of amonafide over 5 days was 3.5% of the total dose. This establishes 1100-1400 mg/m2/day for 5 days as the maximally tolerated dose of amonafide for studies in acute leukemia.
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PMID:Phase I clinical investigation of benzisoquinolinedione (amonafide) in adults with refractory or relapsed acute leukemia. 198 34

Forty-three children with malignant diseases who received 48 totally implanted venous accesses (TIVA) were retrospectively analyzed. More than half the patients had acute leukemia. Mean age was 6 years 10 months. Mean duration of use of the TIVA was 473 +/- 50 days (range 28 to 1,285 da; median 424 days). Removal of the TIVA was required because of an adverse event in 33% of cases. Main reasons for removal included infection (22.9%), thrombosis (6.25%), and catheter dysfunction (4.16%). Catheter-related infections were most often due to staphylococci (90%), especially S. epidermidis (63%). Infection rate was 0.48 per 1,000 patient-days. Flushing with a vancomycin-heparin solution can be expected to decrease this rate. Selection of the implantation site is discussed. In children under 6 years of age, the cephalic vein and external jugular vein are often frail or absent and are therefore less appropriate than the internal jugular vein or subclavian vein.
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PMID:[Clinical experience with totally implantable venous access systems in pediatric hematology and oncology]. 835 96