Dialysis-related genotoxicity: sister chromatid exchanges and DNA lesions in T and B lymphocytes of uremic patients. Genomic damage in patients on hemodiafiltration.

BACKGROUND/AIMS: Patients with chronic renal failure show the presence of massive oxidative genome damage but the role played by dialysis is still a controversial issue. The aim of our study was to verify the genomic damage in B- and T-lymphocyte subpopulations of uremic patients after a single hemodiafiltration session. METHODS: We enrolled 30 patients on maintenance acetate-free biofiltration and 25 age-matched healthy volunteers and studied chromosomal alterations. RESULTS: Our data show that the basal levels of DNA damage, the number of sister chromatid exchanges and basal high-frequency cells levels are significantly higher in patients on hemodiafiltration than in controls and in T lymphocytes than in B cells. CONCLUSIONS: These findings suggest that hemodialytic treatment could represent a potential source of damage, maybe through the oxidative action of the extracorporeal circuit components, which might explain the well-known T-specific immunodeficiency correlated with uremia.

[Hypersplenism: current status and perspectives]. / L'ipersplenismo: attualità e prospettive.

The hypersplenism is a syndrome characterized by cytopenia (involving one or several cellular lines of peripheral blood), increased or normal medullar cellularity, elevated turnover of the involved cellular line. Several studies have emphasized the important role of the spleen as an immunocompetent organ, with a microcirculation and typical functional characteristics. The authors attempt to assess relations between the hypersplenism and splenomegaly, as well as indications, risks and complications of splenectomy in pathological conditions. Finally, the alternative procedures to splenectomy are described.

Translocation (5;10)(q13;q26) in acute monoblastic leukemia.

We report a case of acute monoblastic leukemia [French-American-British (FAB) M5a] observed in a 38-year-old man and associated at diagnosis with a t(5;10)(q13;q26) found in cells from a bone marrow culture. The patient survived only 2 months after diagnosis. t(5;10) as a solitary chromosome abnormality has not been previously reported in M5a, and, in the case that we describe, it appears to be correlated with a poor prognosis.

Severe outcome of hepatitis B virus (HBV) infection and lack of HBV e antigen-defective virus emergence in patients homozygous for HLA class I alleles.

In the Mediterranean region almost all patients with hepatitis B virus (HBV)-related cirrhosis are anti-HBV e antigen (anti-HBeAg)-positive and carriers of HBeAg-negative virus mutants. The six members of a family who acquired HBV infection were recently studied: two siblings developed cirrhosis with persistence of HBeAg positivity, whereas their parents and two more siblings cleared the virus. The two cirrhotic patients showed homozygosity for HLA class I by phenotype, which is a rare occurrence in the general population, while the other family members were heterozygous for HLA class I. The sequencing analyses of the entire viral DNAs isolated from both cirrhotic patients showed that the two viral genomes were almost identical and no mutation preventing HbeAg synthesis or viral gene expression was present. These findings might suggest that homozygosity for HLA class I molecules might be responsible for an insufficient response to the virus, favouring chronic outcome of the infection and the long-lasting persistence of HBV populations that produce HBeAg.

Circulating levels of intercellular adhesion molecule-1 (ICAM-1) and soluble interleukin 2 receptors (IL-2R) in patients with B cell chronic lymphocytic leukaemia.

The serum concentrations of circulating ICAM-1 (cICAM-1) and soluble receptors for interleukin-2 (sIL-2R) were evaluated on 48 patients with B-cell chronic lymphocytic leukaemia (B-CLL) and on 15 healthy control subjects. The mean +/- SD concentration of cICAM-1 was significantly higher (p < 0.002) in B-CLL patients (407.7 +/- 164.3 ng/ml) than in healthy controls (245.4 +/- 76.7 ng/ml). Patients with progressive disease had higher cICAM-1 levels than patients with "indolent" disease (440.38 +/- 32.3 ng/ml versus 321.36 +/- 14.45 ng/ml; p < 0.0001). Serum levels of cICAM-1 were also significantly higher (p < 0.0002) in patients with advanced stage (III-IV) than in those with early stage (I-II). The increase of cICAM-1 levels was positively correlated to increases of soluble receptors for interleukin-2 (r = 0.9; p < 0.0001). These results seem to show that the measurement of serum levels of cICAM-1 may be an useful tool for monitoring disease activity and tumoral mass in patients with B-CLL. However, further studies are needed to define the functional role of high cICAM-1 levels in the immunological dysregulation of patients with malignancy.

Isodicentric Philadelphia chromosome in accelerated phase of chronic myeloid leukemia.

We describe a case of chronic myeloid leukemia (CML) associated with the finding of an isodicentric Philadelphia chromosome [idic(Ph)] during the accelerated phase of the disease. Chromosome study was carried out on bone marrow aspirate cells, obtained and cultured 5 months after the clinical diagnosis. The presence of an isodicentric Philadelphia chromosome was found in 90% of the analyzed metaphases; among the remaining observed metaphases, 6% showed two idic(Ph) chromosomes, 2% a t(9;22), and 2% a normal karyotype. The patient died 7 months after the clinical diagnosis, and 2 months after our chromosome study. The observation of idic(Ph) during CML has seldom been reported and the few cases studied have been inconsistently correlated with the course of the disease. In the present case, the finding of an idic(Ph) and the short patient survival from the time of clinical diagnosis may suggest the observed chromosome aberration as a factor associated with a poor prognosis.