Decrease of dual hepatitis B and C virus infections in children with cancer: changes in risk factors over 30 years.
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Child↗
Biomedical subjects
Robert Debski
Publications and source records attributed to Robert Debski.
Autoimmune hemolytic anemia with giant cell hepatitis: case report and review of the literature.
Autoimmune hemolytic anemia (AIHA) with giant cell hepatitis (GCH) is an uncommon disease in children and is associated with an aggressive and often fatal course. The authors describe a 4-month-old girl who presented with AIHA and elevated liver enzymes. A liver biopsy was consistent with GCH. She was successfully treated with anti-CD20 antibody (rituximab)-containing therapy after failing initial immune suppression therapy. The authors also review the literature for similar cases.
Anemia, Hemolytic, Autoimmune↗
Ex vivo drug resistance profile in childhood acute myelogenous leukemia: no drug is more effective in comparison to acute lymphoblastic leukemia.
Therapy results in childhood acute myelogenous leukemia (AML) differ from those of acute lymphoblastic leukemia (ALL). Cellular drug resistance might be one of the reasons of therapy failure in AML. The aim of the study was the analysis of ex vivo drug resistance profile in childhood initial and relapsed AML in comparison to initial ALL. Fifty-three AML samples were tested for chemosensitivity and results were compared with those of 106 initial ALL samples. Ex vivo drug resistance was tested by means of the MTT assay. Up to 29 cytotoxic drugs were tested for each patient. When compared to de nova ALL samples, myeloblasts from initial AML samples were significantly more resistant to most tested drugs, except cytarabine, mercaptopurine and thioguanine. Relapsed AML samples, in relation to initial AML samples, showed comparable sensitivity to cytarabine, idarubicin, fludarabine and cladribine. Patients, who have died due to refractory or relapsing disease, were already on first diagnosis 2-fold more resistant to cytarabine, 6.4-fold more resistant to cisplatin and 3-fold more resistant to carboplatin, when compared to those who stay in remission. Resistance to prednisolone was observed in 85% initial and all relapsed AML samples, in comparison to 33% of ALL samples. Resistance to cytarabine occurred in 2.1% of ALL and 12% of AML cases while a patient with Down syndrome presented the most sensitive drug resistance profile. In conclusion this study shows that no drug was found which, on average, was more effective in AML than in ALL samples. The sensitivity of myeloblasts to platinum derivatives might have prognostic value.
Carboplatin↗
Course of viral hepatitis B and combined B and C hepatitis in children treated for neoplastic diseases.
BACKGROUND: Viral hepatitis C in children is milder than in adults. Patients with tumors, because of immune deficits, seem to be at risk of rapid liver disease progression. Little is known about the course of HCV and dual HBV-HCV infections in such patients. MATERIAL/METHODS: The study assessed clinical courses of HCV and dual HBV-HCV infections in 249 children with tumors aged 1-18 years, divided into four groups: with HCV infection - 53, HBV-HCV infection - 53, HBV only - 33 and infection-free - 110. RESULTS: Hepatitis C was often chronic - in 83.3% of patients with HCV and 77.3% of those with dual infection. Over 80% had no jaundice. Mean AlAT activity was the highest in the HCV group (149.2I202.7 IU/l), lower in the dual infection group (123.3I148.1 IU/l; p<0.02), and the lowest in HBV (92.7I152.9 IU/l). Transaminasemia course in patients with HCV and dual HBV-HCV infections was most frequently fluctuating (50.9% and 45.3%, respectively). 52.8% of children with HCV demonstrated no advanced inflammatory lesions with invasion of the lamina limitans, no marked fibrosis, and minimum changes in descriptive classification. In 92.3% of children with dual infections, inflammatory activity was mild or mean, with no fibrosis in 61.5%, and persistent chronic inflammation predominant in descriptive classification (46.1%). CONCLUSIONS: HCV and HBV-HCV infections in children with neoplastic diseases tend to take chronic forms, but their clinical course is mild with signs of severe inflammatory activity or hepatic stroma remodeling observed on histopathology.
Adolescent↗
In vitro activity of oxazaphosphorines in childhood acute leukemia: preliminary report.
Glufosfamide (beta-D-glucosyl-ifosfamide mustard) is a new agent for cancer chemotherapy. Its pharmacology is similar to commonly used oxazaphosphorines, but it does not require activation by hepatic cytochrome P-450 and preclinically demonstrates lower nephrotoxicity and myelosuppression than ifosfamide. The aim of the study was a comparison of the drug resistance profiles of glufosfamide and other oxazaphosphorines in childhood acute leukemias. Leukemic cells, taken from children with ALL on diagnosis (n = 41), ALL on relapse (n = 12) and AML on diagnosis (n = 13) were analyzed by means of the MTT assay. The following drugs were tested: glufosfamide (GLU), 4-HOO-ifosfamide (IFO), 4-HOO-cyclophosphamide (CYC) and mafosfamide cyclohexylamine salt (MAF). In the group of initial ALL samples median cytotoxicity values for GLU, IFO, CYC and MAF were 15.5, 33.8, 15.7 and 7.8 microM, respectively. In comparison with initial ALL samples, the relative resistance for GLU and IFO in relapsed ALL samples was 1.9 (p = 0.049) and 1.3 (ns), and in initial AML samples 31 (p < 0.001) and 5 (p = 0.001), respectively. All oxazaphosphorines presented highly significant cross-resistance. Glufosfamide presented high activity against lymphoblasts both on diagnosis and on relapse.
Adolescent↗
Cross-resistance to five glucocorticoids in childhood acute lymphoblastic and non-lymphoblastic leukemia samples tested by the MTT assay: preliminary report.
In vitro antileukemic activity of five glucocorticoids and their cross-resistance pattern in childhood acute lymphoblastic and non-lymphoblastic leukemia were determined by means of the MTT assay in 25 leukemia cell samples of childhood acute leukemias. The equivalent antileukemic concentrations of the drugs tested were: 34 microM hydrocortisone (HC), 8 microM prednisolone (PRE), 1.5 microM methylprednisolone (MPR), 0.44 microM dexamethasone (DX) and 0.22 microM betamethasone (BET). In comparison with initial ALL cell samples, the relapsed ALL group was more resistant to PRE (38-fold, p = 0.044), DX (> 34-fold, p = 0.04), MPR (38-fold), BET (45-fold) and HC (33-fold). The AML cell samples were even more resistant to: PRE (> 85-fold, p = 0.001), DX (> 34-fold, p = 0.004), MPR (> 69-fold, p = 0.036), BET (> 69-fold, p = 0.038) and HC (54-fold, p = 0.059) when compared with ALL on initial diagnosis. A significant cross-resistance among all the glucocorticoids used was found. Only in some individual cases the cross-resistance was less pronounced.
Adolescent↗
The influence of intracellular idarubicin and daunorubicin levels on drug cytotoxicity in childhood acute leukemia.
Uptake and efflux of two anthracyclines, idarubicin (IDA) and daunorubicin (DNR), was studied in childhood acute leukemia samples. A comparison of IDA and DNR transport phenomena in relation to drug cytotoxicity and expression of P-glycoprotein (PGP) was made. Intracellular content of IDA/DNR was determined by flow cytometry using the fluorescent properties of the drugs. In vitro drug cytotoxicity was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. PGP expression was analysed by flow cytometry. The uptake and efflux rates were non-significantly higher for IDA than DNR. There were no differences between three types of leukemia with respect to drug content during accumulation and retention. After correction for the cell volume, intracellular concentration of both drugs in each moment of uptake and efflux was significantly lower in relapsed ALL and AML samples in comparison with initial ALL cells. Efflux, but not uptake, of both drugs was inversely correlated with PGP expression and IDA, but not DNR, cytotoxicity. The cytotoxicity was correlated with drug accumulation for both drugs and with drug retention for IDA. In conclusion, it seems that (1) intracellular content was related to the lipophilic properties of the drugs rather than to the type of leukemia, (2) decreased intracellular concentration of both drugs might have an impact on compromised therapy results in AML and relapsed ALL children, (3) IDA presents higher cytotoxicity, which possibly might be decreased by the presence of PGP. These results might have a practical impact on the rational design of new chemotherapy protocols.
ATP Binding Cassette Transporter, Subfamily B, Mem↗