Renal complications associated with human parvovirus B19 infection in early childhood.

A previously healthy two-year-old girl presented with proteinuria and macroscopic haematuria. Laboratory findings included haemolytic anaemia with thrombocytopenia. Interestingly, continuing reticulocytopenia was noted. Therefore an acute parvovirus B19 infection was suspected, which could be confirmed by serological and molecularbiological evidence. This case report underlines renal complications of parvovirus B19 infection in early childhood including haemolytic-uraemic syndrome (HUS)-like episodes, and potential pathogenetic mechanisms are discussed.

Multi-organ affecting CMV-associated cryoglobulinemic vasculitis.

We report on a 67-year-old female patient who was admitted to our intensive care unit with acute renal failure and severe hypoxemia. Transiently, the patient had to be treated with kidney replacement therapies and artificial ventilation. The actual illness started with general weakness, recurrent bloody diarrhea and intermittent dermatitis of the lower legs. Skin symptoms were initially observed 2 years before the actual clinical findings. The bloody diarrhea was attributed to an inflammatory stenosis of the sigma. The life-threatening clinical aggravation was due to diffuse alveolar hemorrhage and alveolitis. In the search for the cause of the systemic disease, both a monoclonal y-globulinemia, causing a cryoglobulinemia type II and an acute cytomegalovirus infection were diagnosed. Additionally, the course of the disease was complicated by a secondary antibody deficiency as well as an endocarditis of the aortic valve caused by Enterococcus faecium. A cryoglobulinemic vasculitis type II was histologically found in biopsy specimen of the kidney. Thus, the present case reports on a coincidence of a monoclonal gammopathy causing a cryoglobulinemia type II with extensive organ involvement and a florid CMV infection. We hypothesize that the CMV infection has triggered the cryoglobulinemia and its particular severe organ involvement.

Passenger lymphocyte syndrome with severe hemolytic anemia due to an anti-Jk(a) after allogeneic PBPC transplantation.

BACKGROUND: After allogeneic peripheral blood progenitor cell (PBPC) transplantation, a patient developed a severe hemolytic transfusion reaction due to passenger lymphocyte syndrome. CASE REPORT: A 50-year-old woman with secondary acute myeloid leukemia transforming from a myelodysplastic syndrome received an ABO-compatible PBPC graft from her HLA-identical sister. For prophylaxis of GVHD, the patient was treated with cyclosporine and methotrexate. Eighteen days after the transplant, the patient experienced a severe hemolytic transfusion reaction due to an alloantibody (anti-Jk(a)) produced by donor lymphocytes. RESULTS: The patient was typed as group A, Jk(a+) before transplantation; the donor was typed as group A, Jk(a-). On Day 18 after transplantation, the immunohematologic screening revealed a positive DAT (C3d 3+) and an alloanti-Jk(a). Hemolysis in the patient at that time was indicated by a drop in the Hb and an increase in the LDH level (maximum, 592 IU/L on Day 23). CONCLUSION: The course of hemolysis and the time of appearance of an alloantibody in this patient meet the criteria for passenger lymphocyte syndrome. In most cases, this syndrome is triggered by ABO system antibodies. This is the first reported case of passenger lymphocyte syndrome after PBPC transplantation that was due to an alloantibody that did not belong to the ABO system.

DNA repair and cellular resistance to alkylating agents in chronic lymphocytic leukemia.

The time course of the formation and persistence of repair-induced DNA lesions such as single-strand breaks (SSBs) were determined in isolated lymphocytes derived from 32 patients with chronic lymphocytic leukemia (CLL) using the single-cell gel electrophoresis (SCGE, "comet") assay. After pulse-exposure to N-ethyl-N-nitrosourea (EtNU), the initial amount of SSBs (t0 SCGE values) and the time periods required to reduce DNA damage by 50% (t50% SCGE values) were determined in nuclear DNA of individual cells. The t0 SCGE and t50% SCGE values varied interindividually between CLL specimens by factors of 16.6 and 8.2, respectively. Regarding cell-to-cell variation, no major subpopulations with significantly different DNA repair capacities were observed in cell specimens from a given patient. In addition, a monoclonal antibody-based immunocytological assay was used to determine the elimination kinetics for the cytotoxic alkylation product O6-ethylguanine from nuclear DNA. A strong correlation was observed between the relative times for SSB repair and the elimination of O6-ethylguanine from nuclear DNA. Because SCGE and immunocytological assay measure different steps of DNA repair, this observation suggests coordinated regulation of the respective repair pathways. With regard to chemosensitivity profiles, a "fast" repair phenotype corresponded to enhanced in vitro resistance to EtNU, 1,3-bis(2-chloroethyl)-1-nitrosourea, or chlorambucil. Accelerated SSB repair and pronounced in vitro resistance to chlorambucil, 1,3-bis(2-chloroethyl)-1-nitrosourea, and EtNU were found in lymphocytes from CLL patients nonresponsive to chemotherapy with alkylating agents. Distinct DNA repair processes thus mediate resistance to alkylating agents in CLL lymphocytes.

Chemosensitisation of alkylating agents by pentoxifylline, O6-benzylguanine and ethacrynic acid in haematological malignancies.

The effects of resistance modifiers (RM) on the cytotoxicity of mafosfamide (MAF), bis-chloroethylnitrosourea (BCNU) and dacarbazine (DTIC) were evaluated by the MTT colorimetric assay in isolated lymphocytes and blast cells derived from patients with chronic lymphatic leukaemia (CLL; n = 28) and acute myeloid leukaemia (AML; n = 30), or from healthy donors (n = 19). Pentoxifylline (PTX) has been shown to restore sensitivity to alkylating drugs by interfering with DNA repair. PTX (10 microM) significantly sensitised leukaemic blasts to the cytotoxic effect of MAF. In 8 out of 30 AML samples, sensitisation ratios (SRs; i.e. cytotoxic drug ID50s in the presence or absence of RM) for MAF in the presence of PTX were > 2 ranging up to 4.2. Inhibition of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) by O6-benzylguanine (O6-BG; 50 microM) enhanced the cytotoxicity of DTIC in CLL lymphocytes. SRs > 2 for DTIC in the presence of O6-BG were observed in 7 out of 28 CLL specimens. Sensitisation was generally greater in the more chemo-resistant specimens. Ethacrynic acid (EA; 1 microM), an inhibitor of glutathione-S-transferases (GST), failed to influence the cytotoxicity of alkylating agents in any cell type. Also, all examined RMs did not sensitive leukaemic cells to the cytotoxic effect of BCNU. The data show significant chemosensitisation of leukaemic cells to alkylating agents by PTX and O6-BG, indicating a potential clinical use of these substances as RM in patients.