Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Soft tissue infections were seen in 25 patients with underlying malignancy and immunosuppressive disease. The primary disease included leukemia, lupus, aplastic anemia, lymphoma, carcinoma and myeloma. Infectious sites included the perianal area, gluteal, chest wall, extremity and the vulva. Eighty per cent of the infectious episodes occurred in patients who were granulocytopenic. Initial presentation was of local tenderness and redness. Fluctuation and discoloration were present in nine patients who were also hypotensive. Local drainage in five patients resulted in the death of two (20%). Overall, the mortality was 3/25 (12%). Wide debridement and drainage and appropriate antibiotic therapy resulted in the death of 1/20 (5%) patients. Hypotension, discoloration and fluctuation were found to be late signs in these patients. Soft tissue infections in the compromised host present subtly and progress to death if treatment is delayed. Temperature elevation and localized tenderness and erythema are indications for broad spectrum antibiotics and extensive intraoperative drainage and debridement.
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PMID:Soft tissue infections in the compromised host. 338 98

The effect of 3-deazauridine (DAUR) on the intracellular purine and pyrimidine nucleotide pools and on the metabolism of azacitidine (aza-CR) in L1210 cells, sensitive (L1210/0) and resistant (L1210/ara-C) to cytarabine (ara-C), was examined. The consequences of such a modulation were correlated with the therapeutic efficacy of this combination in mice bearing L1210 leukemia. In vitro and in vivo treatment of both L1210 sublines with DAUR produced a dose- and time-dependent reduction in the CTP and dCTP pools and an increase in the UTP pool. In addition to these changes in the pyrimidine nucleotide pools, DAUR produced a modest increase in the GTP pool and a marked expansion of the ATP pool in L1210/ara-C 12 hrs following in vivo drug treatment. These perturbations in nucleoside triphosphate pools were more pronounced in L1210/ara-C cells. Treatment of mice bearing L1210/ara-C with 100 mg/kg of DAUR reduced the CTP and dCTP pools in the leukemic cells by greater than 90% within 1-3 hrs after administration of the drug, with complete recovery of these pools occurring within 12 hrs. Fluctuation of the pyrimidine nucleoside pools after DAUR treatment was correlated with the subsequent increase in aza-CR metabolism and its incorporation into RNA and with the potentiation of the in vivo toxicity of aza-CR. In mice bearing L1210/0 or L1210/ara-C tumors, DAUR or aza-CR produced a less than or equal to 23% increase in life-span (ILS). Administration of aza-CR 3 hrs after DAUR, however, produced about an 80% ILS among mice bearing L1210/ara-C tumors, but no more than an approximately 20% ILS among mice bearing L1210/0 tumors. These data suggest that the therapeutic activity of the sequential combination of DAUR and aza-CR against mice bearing L1210/ara-C cannot be explained, per se, on the basis of the initial intracellular modulation of nucleotide pools, since DAUR affected these pools of the two tumors to approximately the same degree. What appears to be important, however, is that such a modulation by DAUR preferentially affected the metabolism of aza-CR in leukemic cells resistant to ara-C which are devoid of deoxycytidine kinase activity.
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PMID:Effect of 3-deazauridine on the metabolism, toxicity, and antitumor activity of azacitidine in mice bearing L1210 leukemia sensitive and resistant to cytarabine. 619 May 58

To assess the immunopathological significance of the increased replication of human T-cell leukemia virus type I (HTLV-I) in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) we investigated the dynamics of HTLV-I proviral DNA in peripheral blood mononuclear cells (PBMC) of HAM/TSP patients at different clinical stages. We compared the dynamics to those of asymptomatic HTLV-I carriers (AC). The estimation of the amount of HTLV-I proviral DNA was carried out by quantitative polymerase chain reaction of serially diluted DNA samples where it was feasible to titrate 0.04-80 copies per 100 PBMC. The proviral DNA quantified in six patients with HAM/TSP was 2-20 copies per 100 PBMC, while that in eight cases of AC was 0.04-8 copies per 100 PBMC. Thus, the amount of HTLV-I proviral DNA in HAM/TSP patients was 3-50 times as high as that of AC. When we followed up HAM/TSP patients for 1-3 years, the amount of HTLV-I proviral DNA fluctuated from 4 to 10-fold. These data suggest that the rate of HTLV-I replication increases in HAM/TSP and the amount of HTLV-I proviral DNA fluctuates in their clinical course. Fluctuation in the amount of HTLV-I proviral DNA may reflect dynamics of HTLV-I infected cell proliferation and immunological suppression in vivo in HAM/TSP patients.
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PMID:Fluctuation of HTLV-I proviral DNA in peripheral blood mononuclear cells of HTLV-I-associated myelopathy. 842

Many adult T-cell leukaemia/lymphoma (ATLL) patients who respond to induction treatment, then relapse. Knowing the clonality pattern of residual tumourous clones during treatment could help understand disease evolution and aid therapeutic decisions. We developed a sensitive and semi-quantitative molecular analysis of these clones in ATLL patients. DNA samples from PBMCs derived from eight ATLL patients were studied over time by quadruplicate linker mediated PCR (LMPCR) amplification of HTLV-1 integration sites. Patients were treated with combination chemotherapy, zidovudine-interferon-alpha and/or by peripheral stem cell transplantation or allogeneic bone marrow transplantation. Persistence of tumourous clones at a high frequency (>1/300 PBMCs) was frequently observed, even in complete responders, and was invariably correlated with relapse and/or poor outcome. Fluctuation in the frequency of some tumourous clones was observed with evidence for clonal change under treatment in one patient, indicating that treatment of ATLL can result in the selection of resistant clones. Finally, allogeneic bone marrow transplantation (BMT) using an HTLV-1 infected sibling as donor was found to be associated with long-lasting disappearance of tumourous clones and a possible cure of the disease. Long-term persistent clonal expansion of circulating HTLV-1 bearing T cells which derived from the donor bone marrow was evidenced in this patient. In conclusion, variable success in treatment of ATLL is probably due to the clonal heterogeneity which results in the selection of resistant clones. Semi-quantitative assessment of residual disease (RD) through LMPCR may predict treatment failure. Accordingly, additional therapy may be tailored to the clonality pattern observed after first-line therapy.
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PMID:Semiquantitative analysis of residual disease in patients treated for adult T-cell leukaemia/lymphoma (ATLL). 1035 40