PURPOSE: To evaluate the prognostic significance of five scoring systems applied with predictive trends to myelodysplastic syndromes (MDS). PATIENTS AND METHODS: This study was comprised of 226 patients with MDS diagnosed in accordance with the FAB criteria and followed up in our department between January 1975 and April 1992. The following MDS subtypes were found: refractory anaemia (RA), 59 cases; refractory sideroblastic anaemia (RSA), 49 cases; refractory anaemia with excess of blasts (RAEB), 56 cases; RAEB in transformation (RAEB-T) 48 cases; and chronic myelomonocytic leukemia (CMML), 14 cases. The following scoring systems were applied: Mufti's 1985, Varela's 1985, Sanz's 1989, Rubio's 1991 and Aul's 1992. The statistical analysis was performed according to Kaplan-Meier actuarial systems and the log-rank test of survival. RESULTS: (1) Three groups (A, B and C) can be defined by Mufti's system, with median survival of 54.0, 16.0 and 8.5 months, respectively. The majority of cases (138) were included in group B. Group A did not reach 25 per cent of actuarial survival probability, whereas groups B and C did at 31.1 and 12.2 months, respectively. With regard to the morphologic subtypes, RA and RSA were included in groups A and B, and RAEB, RAEB-T and CMML pertained mostly to group C. Sixty-six cases (33.6 per cent) developed into acute leukemia (AL) corresponding to those last groups. (2) The three groups defined by Varela's system (0-1, 2-5 and 6 or more) had median survival of 91.8, 24 and 13 months, respectively. As in the former system, group 0-1 did not reach 25 per cent actuarial probability, this appearing at 60 and 20 months, respectively, in groups 2-5 and > 6. The distribution of the cytological varieties, RA and RSA among the groups is heterogenous although they were more common within the cases included in groups 0-1. All cases developing AL were included in the groups 2-5 and > 6. (3) The three groups of the system proposed by Sanz (0-1, 2-3 and 4-5) had median survival of, 55.3, 15 and 12.6 months respectively. As in the preceding cases, group 0-1 did not reach the 25 per cent actuarial probability, while this figure appeared at 28.2 months for group 2-3 and at 19.3 months for group 4-5. RA and RSA varieties were included chiefly in group 0-1, while RAEB and RAEB-T appear mostly in groups 2-3 and 4-5. The distribution of the cases and the evolution of AL was heterogeneous according to this system, although they predominate in groups 2-3 and 4-5. (4) Using the Aul's system, three groups A, B and C were defined. The median survival time was 14 months for group C and 24 months for group B. For group A, the median survival was not reached. RA and RSA were exclusive for group A, while RAEB and RAEB-T varieties were outstanding in group C. Regarding the evolution to leukemia the differences observed had no statistical relevance. (5) Three prognostic groups were defined by Rubio's system (namely 0-2.5, 3-5.5, > or = 6) with median survival of 53.3, 16.8 and 10.5 months, respectively. A striking difference was seen when studying the cumulated survival observed, in each of the three percentages considered, between the groups. The different cytological varieties were reasonably distributed with higher incidence of RA and RSA in group I and RAEB, RAEB-T and CMML in group III. This system offers statistical significance when comparing RA with RSA, RAEB with RAEB-T and, obviously RA+RSA with RAEB+RAEB-T+CMML. The evolution into AL also showed statistical significance with respect to the three groups.

Adult↗

PubMedDate not supplied

Mutation prevalence among 51 unrelated Spanish patients with Gaucher disease: identification of 11 novel mutations.

Gaucher disease is an autosomal recessive disorder caused by mutations in the lysosomal beta-glucocerebrosidase (GBA) gene. Gaucher disease is a very heterogeneous entity due to the large number of different mutations existing in the GBA gene, resulting in a defective protein whose impaired activity is the cause of the disease. We present a mutation analysis of the GBA gene in 51 unrelated Spanish Gaucher disease patients together with clinical findings. Two common mutations, c.1226A>G (N370S) and c.1448T>C (L444P), were determined by restriction enzyme digestion after PCR amplification of genomic DNA. The remaining alleles were screened by amplifying the entire GBA gene followed by nested PCR and SSCP analysis under four different conditions. The c.1226A>G (N370S) and c.1448T>C (L444P) mutations were common, accounting for 56 alleles (55%) and 16 alleles (15%), respectively. In addition, 25 different mutations were found, 11 of which are described here for the first time: c.(-203)A>G, c.160G>A (V15M), c.256C>T (R47X), c.445-2a>g (IVS4-2a>g), c.485T>C (M123T), c.914C>T (P266L), c.953delT, c.1124T>C (L336P), c.1207A>C (S364R), c.1214delG,C, and c.1510delT,C,T (465delSer). Two mutations, S364R and P266L, were associated with neuronopathic forms of Gaucher disease: S364R mutation in heterozygosity with the L444P mutation and the P266L mutation in a homozygous state. Two type 1 patients were found to be carriers of two mutations in the same allele (genotypes [N370S] + [E326K + N188S] and [N370S] + [IVS4-2a>g+c.(-203)A>G]). This study allowed us to identify 100% of mutant alleles, and therefore we conclude that the method used to screen for mutations in the GBA gene is very reliable and there is a broad spectrum of mutations in the GBA gene in the Spanish population.

Adolescent↗

PubMedDate not supplied

Enhanced glutathione S-transferase (GST) activity in pregnant rats treated with benzo(a)pyrene.

Administration of Benzo(a)pyrene (BP, 50 mg/kg/d) to pregnant rats significantly increased Glutathione S-transferase (GST) activity in placental tissue-extract (Vmax = 40 nmol/min/mg protein and 69 nmol/min/mg protein in controls versus treated animals respectively; P less than 0.01) and total fetal tissue-extract (Vmax = 51 nmol/min/mg protein and 82 nmol/min/mg protein in controls versus treated animals respectively; P less than 0.01) indicating an induction effect of BP on the GST system. An increase in the Km values was also observed: 1.61 x 10(-3) M and 2.84 x 10(-3) M in control versus treated placentae; 1.38 x 10(-3) M and 2.05 x 10(-3) M in control versus treated fetuses. A competitive effect on the enzyme by the BP present in the sample may also be involved. The glutathione content in both tissues did not show any changes after the treatment with BP. This increase in the GST system was not sufficient to protect the fetus. BP affected the reproductive performance of pregnant rats by significantly increasing the number of resorptions and fetal wastage, and, also, by decreasing the fetal weight.

Animals↗