Painful vaso-occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso-occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso-occlusive crisis occurrence, we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso-occlusive crisis and steady-state conditions. Compared to steady-state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxidase, RBC caspase-3 activity, as well as the concentrations of total, neutrophil- and RBC-derived microparticles were increased during vaso-occlusive crises, whereas the reduced glutathione content was decreased in RBCs. In addition, natural anti-band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products and RBC caspase-3 activity. These data showed an exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates.

Three major types of mRNA can be expressed as a result of the Philadelphia translocation, dependent on the position of the break within the BCR gene on chromosome 22. In addition, alternative splicing of the mRNA transcribed from the BCR/ABL fusion gene has been reported and it has been suggested that this may play a role in the generation of the acute phase of Philadelphia positive chronic myeloid leukaemia (CML). We have examined the fusion RNA present in 24 cases of chronic phase CML and 21 cases of patients with CML in blast crisis using the polymerase chain reaction. In no case was it possible to detect the presence of the e1a2 junction which encodes the p190 hybrid protein product. We conclude that the acquisition of the p190 does not play a significant role in the generation of the blast crisis of CML. Neither could we detect a significant difference in the number of cases which simultaneously express both b2a2 and b3a2 junction products in samples isolated from chronic phase and blast crisis. In the series analysed by ethidium bromide stained gels, there was, however, an increase in the percentage of cases expressing the b3a2 junction in the mononuclear cells of blast crisis patients as compared to the white blood cells of patients in chronic phase.

We performed Southern-blot analysis of the p53 gene in 41 consecutive patients with typical chronic myelocytic leukemia (CML). In two of them, we were able to study cells during both the chronic and the accelerated phases. Only one of the 29 chronic-phase samples had rearrangement of the p53 gene, whereas three of the nine accelerated-phase samples and one of the five patients in blast crisis exhibited rearrangements. Gene deletion was observed in two patients, one in accelerated phase and the other in blast crisis. One patient with a nonrearranged p53 gene in chronic phase showed rearrangement after progression to the accelerated phase. On the other hand, one patient in accelerated phase exhibited rearrangements which disappeared after reversion to chronic phase with successful treatment. Our findings support the opinion that alterations of the p53 gene may play an important role in CML evolution.

Cytogenetic and molecular techniques were performed on samples obtained from 29 patients with chronic myelocytic leukemia (CML); 27 were in the chronic phase and two were in blast crisis. A further five cases were also analyzed, two with atypical CML (aCML), one with chronic neutrophilic leukemia (CNL), and two with juvenile CML (JCML). Most of the cases with typical CML were Philadelphia chromosome (Ph) positive and had a rearrangement within the major breakpoint cluster region (M-bcr). One of these cases was shown to be Ph positive but showed no rearrangement within the M-bcr. Two cases with clinical features typical of CML were Ph negative. One of these showed a rearrangement within the M-bcr, but no rearrangement was demonstrated in the other. Both patients in blast crisis were Ph positive and M-bcr positive. One showed a second Ph. Patients with aCML were Ph negative and had no M-bcr rearrangement. A polymorphism within the M-bcr was found with BglII in one case. No Ph chromosome or M-bcr rearrangement was found in CNL or JCML. These data support the molecular heterogeneity reported in CML.

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Molecular characterization of the alpha-thalassemia mutations present in nine HbH subjects from Cuba was achieved by digestion with Bam HI, Bgl II, and Apa I and hybridization with alpha- and zeta-specific probes. The results show that the molecular basis of the genetic defect is quite homogeneous, all the subjects carrying the - alpha 3.7 type I/--SEA genotype. Variations are observed in the size of the zeta polymorphic fragments.

Resumen: El desarrollo del Sistema Nervioso (SN) está afectado en los pacientes con Anemia Drepanocítica (AD). La Resolución Temporal Visual (RTV) es considerada como una medida de la velocidad de procesamiento y de activación cortical. Se utiliza como indicador general del funcionamiento del SN y puede evaluarse mediante la Frecuencia Crítica de Fusión (FCF). Se midió la FCF en 84 pacientes sin antecedentes de eventos neurológicos, en edades entre 8-68 años, y en controles sanos. Se midió el valor de la hemoglobina (Hb) de los pacientes al momento de la evaluación neuropsicológica. La FCF de los pacientes fue significativamente más baja. La edad correlacionó inversamente con la FCF; no se hallaron associaciones estatisticamente significativas entre los valores de la Hb y los resultados de la FCF. Se concluye que la RTV está disminuida en los pacientes con AD, lo que sugiere la existencia de afectación del neurodesarrollo como resultado de la enfermedad.Palabras clave: anemia drepanocítica; neurodesarrollo; neurocognición; resolución temporal visual. VISUAL TEMPORAL RESOLUTION IN PATIENTS WITH SICKLE CELL ANEMIA Abstract:The Nervous System (NS) is affected in patients with Sickle Cell Anemia (SCA). The Visual Temporal Resolution (VTR) is considered as a measure of processing speed and cortical activation. It is used as general indicator of NS functioning, and it can be tested by Critical Frequency Fusion (CFF). The CFF was examined in 84 patients without previous neurologic events and the same amount in healthy subjects. The participants were ranging in age from 8 to 68. The patients' hemoglobin level was measured at the moment of the neuropsychological assessment. The patients' CFF was significantly lower than healthy people. Age correlated inversely with CFF, and statistically 1 Endereço para correspondência: Raúl Martinez Triana.