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Biomedical subjects

L Font

Publications and source records attributed to L Font.

At least 19 recordsLinked to original sources

Exposure to non-arsenic pesticides is associated with lymphoma among farmers in Spain.

OBJECTIVES: To estimate the risk of lymphoma among farmers in Spain. METHODS: This is a multicentre case control study conducted in Spain. Cases were subjects diagnosed with lymphoma according to the World Health Organization (WHO) classification in four hospitals between 1998-2002. Hospital controls were frequency matched to the cases by sex, age, and centre. All subjects were interviewed about jobs ever held in lifetime for at least one year and the exposures in those jobs were recorded. The risk of lymphomas among subjects ever having had a job as a farmer was compared with all other occupations. Farmers were analysed according to the type of farming job performed: crop farming, animal farming, and general farming. Occupational exposure was summarised into 15 main categories: organic dust, radiation, contact with animals, PAH, non-arsenic pesticides (carbamates, organophosphates, chlorinated hydrocarbons, triazines and triazoles, phenoxy herbicides, chlorophenols, dibenzodioxin, and dibenzofuran), arsenic pesticides, contact with meat, contact with children, solvents, asbestos, soldering fumes, organic colourants, polychlorinated biphenyls, ethylene oxide, and hair dyes. RESULTS: Although farmers were not at an increased risk of lymphoma as compared with all other occupations, farmers exposed to non-arsenic pesticides were found to be at increased risk of lymphoma (OR = 1.8, 95% CI 1.1 to 2). This increased risk was observed among farmers working exclusively either as crop farmers or as animal farmers (OR = 2.8, 95% CI 1.3 to 5.8). Risk was highest for exposure to non-arsenic pesticides for over nine years (OR = 2.4, 95% CI 1.2 to 2.8). CONCLUSIONS: Long term exposure to non-arsenic pesticides may induce lymphomagenesis among farmers.

Adult↗

Variable very-high-energy gamma-ray emission from the microquasar LS I +61 303.

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and can be used to elucidate the physics of relativistic jets. We report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I 61 + 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, which suggests that the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or absorption processes.

Journal Article↗

Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics [t(8;21) and inv(16)].

Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with current anthracycline- and cytarabine-based protocols. Tandem analysis with flow cytometry (FC) and real-time RT-PCR (RQ-PCR) was applied to 55 patients, 28 harboring a t(8;21) and 27 an inv(16), including one case with a novel CBFbeta/MYH11 transcript. A total of 31% (n=17) of CR patients relapsed: seven with t(8;21) and 10 with inv(16). The mean amount of minimal residual disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly different: 0.3 vs 0.08% (P=0.002) at the end of treatment. The mean number of fusion transcript copies/ ABL x 10(4) also differed between relapsed and non-relapsed patients: 2385 vs 122 (P=0.001) after induction, 56 vs 7.6 after intensification (P=0.0001) and 75 vs 3.3 (P=0.0001) at the end of chemotherapy. Relapses were more common in patients with FC MRD level >0.1% at the end of treatment than in patients with < or = 0.1%: cumulative incidence of relapse (CIR) was 67 and 21% (P=0.03), respectively. Likewise, using RQ-PCR, a cutoff level of >10 copies at the end of treatment correlated with a high risk of relapse: CIR was 75% for patients with RQ-PCR >10 compared to 21% for patients with RQ-PCR levels < or = 10 (P=0.04). Combined use of FC and RQ-PCR may improve MRD detection, and provide useful clinical information on relapse kinetics in AML patients.

Acute Disease↗

Uncertainty, variability and sensitivity analysis applied to the RAGENA model of radon generation, entry and accumulation indoors.

The application of a radon model is useful to understand the processes that drive the radon gas behaviour from its sources to its accumulation indoors. Since in a given inhabited house the detailed knowledge of the values of all the parameters that affect indoor radon levels is not available, the response of the model has to be explored in a reference site in which all the parameters are supposed to be known. We call this site the reference configuration. In this paper we report on the procedure followed to carry out uncertainty, sensitivity and variability analysis of the model response for a reference configuration that corresponds to a single family multi-zone house. We have obtained from the uncertainty analysis that, assuming a normal distribution of all the input parameters with a 10% relative standard deviation (R.S.D.), the model outputs present a R.S.D. in the range 17-22%. The sensitivity analysis reflects, in general, a good behaviour of the model, in the sense that its response describes a realistic behaviour of the system. The variability analysis has shown that the model is applicable to a wide range of situations, and that the most relevant parameters for the reference configuration are: the soil gas-permeability (obtained from the mean soil grain diameter); the ventilation rate of the rooms; the air-exchange rate between the basement and room 2; the soil-indoor pressure difference; the open area; and the concrete radium content.

Journal Article↗

Increased conventional chemotherapy does not improve survival in multiple myeloma: long-term results of two PETHEMA trials including 914 patients.

BACKGROUND: Melphalan and prednisone (MP) has been the standard treatment for multiple myeloma (MM) for the last 30 years. Combination chemotherapy at conventional doses has not shown a significant prolongation of survival when compared to MP. There are few data comparing conventional chemotherapy at standard doses with conventional treatment at higher doses. We present the long-term outcome of 914 patients from two randomized trials comparing three different dose intensity regimens. METHODS: From 1 January, 1985 to 31 December, 1989, 487 patients were randomized between MP (melphalan 9 mg/m(2) p.o. and prednisone 60 mg/m(2) days 1-4) and alternating VCMP (vincristine 1 mg i.v. on day 1, cyclophosphamide 500 mg/m(2) i.v. on day 1, melphalan 6 mg/m(2) p.o. on days 1-4, and prednisone 60 mg/m(2) on days 1-4) and VBAP (vincristine 1 mg i.v. on day 1, BCNU and doxorubicin 30 mg/m(2) i.v. each on day 1, and prednisone 60 mg/m(2) on days 1-4). From 1 January, 1990 to 31 May, 1994, 427 patients were randomized between VCMP/VBAP at the above detailed doses (VCMP/VBAP 'SD') and the same regimen increasing the doses of cyclophosphamide and doxorubicin from 500 to 1200 mg/m(2) and from 30 to 50 mg/m(2), respectively (VCMP/VBAP 'HD'). RESULTS: Increasing dose intensity produced a significantly higher partial response rate (31% vs 45% vs 51% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P < 0.01). However, a significantly early death rate was observed in the HD arm (7.7, 7.5 and 12.1% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = 0.05). Median duration of response (20 vs 18 vs 19 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) and median survival (25 vs 31 vs 29 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) were similar in the three groups. MP produced a higher degree of thrombocytopenia than combination chemotherapy at standard (P = 0.002) or high dose (P = 0.01), this leading to a significantly higher dose reduction in the MP arm (P < 0.001 and P = 0.003 for VCMP/VBAP 'SD' and VCMP/VBAP 'HD', respectively). CONCLUSION: In these trials the response rate significantly correlated with the regimen intensity. However, no significant differences in response duration and survival were found. This highlights the limited role of conventional chemotherapy in MM and the need for further trials, aimed at determining the impact of new treatment approaches such as high-dose therapy/autotransplantation.

Antineoplastic Combined Chemotherapy Protocols↗

Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group.

BACKGROUND AND OBJECTIVE: Anemia leading to transfusion is probably the most important problem in patients with myelodysplastic syndromes (MDS). Human recombinant erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) have been used to treat patients with anemia of MDS, but fewer than 50% respond. The aim of this work was to evaluate the benefit of rHuEpo +/- G-CSF treatment and to isolate the response predictive variables in a group of selected patients with MDS. DESIGN AND METHODS: A non-randomized multicenter trial was carried out in 32 patients with MDS. The inclusion criteria were age >= 18 years, refractory anemia (RA) or refractory anemia with ringed sideroblasts, Hb <= 100 g/L or receiving transfusions and serum erythropoietin <= 250 U/L. These patients were treated with subcutaneous rHuEpo (300 U/kg) three times a week for 8 weeks. In the case of partial response (PR) or no response (NR) subcutaneosly administered G-CSF (1 microg/kg) three times a week was added to the rHuEpo for 8 more weeks. If the patient achieved complete response (CR) or PR in the second phase, he was included in a follow-up phase of 24 weeks in which the dose of growth factors was tapered down. Several variables, including the score published by the Scandinavian-American group, were used as possible predictive variables. RESULTS: An erythroid response was observed in 16 patients (50%); in 12 it was a CR and in 4 it was a PR. During the period of rHuEpo administration, 7 CR and 4 PR (34.4%) were documented. Of the 14 patients in whom G-CSF was added to rHuEpo, 7 (50%) responded (3 CR and 4 PR). No major side-effects associated with growth factors were observed. The multivariate analysis showed that of the different variables evaluated only the Scandinavian-American response score was significant with a relative probability of response of 11.8 (95% confident intervals: 2.5-53) when this score was > +1 (77% of cases responded). In contrast, when this score was <= 1 only 15 % of the cases responded. INTERPRETATION AND CONCLUSIONS: Use of the Scandinavian-American response score is to be recommended in a patient-oriented approach to treating MDS cases with the Epo and G-CSF. Treatment with rHuEpo and G-CSF is safe, its main drawback being its cost. However, a long-term study evaluating the regimen's cost-benefit ratio is warranted.

Adult↗

[Molecular analysis of glucose-6-dehydrogenase deficiency in Spain].

PURPOSE: G6PD deficiency is the most frequent enzymopathy-producing genetic polymorphism in humans. Up to now, over 400 putative variants of G6PD have been distinguished on the basis of biochemical characterization of the deficient enzyme. Analysis of the G6PD gene has made possible a precise classification of the G6PD molecular variants by identification of about 80 different point mutations causing much of the phenotypic heterogeneity. In the Spanish population, the analysis of G6PD has led to the identification of 15 different point mutations that underlay the phenotypic heterogeneity of G6PD previously reported by biochemical analysis. The purpose of the study has been to identify the genetic mutation responsible of the G6PD deficiency and to improve the knowledge of its genetic homogeneity. PATIENTS AND METHODS: From 50 Spanish males with G6PD deficiency 34 came from out consultation and 16 from the Spanish Study Group on Red Cell Pathology (GEHBTA-Eritropatología) The methods employed included screening of prevalent mutations by ER-PCR, SSCP-PCR, genetic segmentation and biochemical characterization of the deficient enzyme. RESULTS: In 31 cases the mutations were characteristic of the four most frequent polymorphic variants found in Spain (G6PD A-376G/202A, G6PD Mediterranean 563T G6PD Union 1360T and G6PD Seattle 344C). Since these mutations either create or abolish a specific site recognized by a restriction endonuclease (RE), they can be rapidly detected by RE digestion of a PCR-amplified product (PCR-RE). In patients where none of these mutations were present (17 cases), the G6PD gene was subjected to PCR single-strand conformation polymorphism (PCR-SSCP) analysis combined with direct PCR-sequencing. By using this procedure, 9 new mutations have been identified, five of them have been also found in other geographical areas and were associated with favism (G6PD A-376G/968C, G6PD Santamaria 376G/542T, G6PD Aures 143C and G6PD Chatham 1003A) or chronic haemolytic anaemia (G6PD Tomah 1153C). The other four mutations are unique and not reported so far: Three of them are associated with favism (G6PD Málaga 542T, G6PD Murcia 209G and G6PD Valladolid 406T) and one with chronic haemolytic anaemia (G6PD Madrid 1155G). The remaining eight cases are under study. CONCLUSION: The present study confirms the marked genetic heterogeneity of G6PD deficiency in Spain and demonstrate that the PCR-RE analysis is an easy tool for rapid diagnosis of the molecular defect in subjects with the common forms of G6PD deficiency. Furthermore the fact that G6PD A-376G/202A is the most common variant within Spanish population and the finding of G6PD Aures 43C and G6PD Santamaría 76G/542T, who are polymorphic in Algeria is consistent with a significant gene flow from Africa to Europe through Spain.

Africa, Northern↗

[Monocytoid B-cell lymphoma: clinico-pathologic study of 2 cases].

Monocytoid B-cell lymphoma, considered as a low-grade lymphoma, is seen most frequently in persons of advanced age, chiefly women. It is often diagnosed in lymph-node phase, in low stages (I-II), and peripheral blood, bone-marrow or spleen are seldom involved. The morphologic and immunohistochemical study of two patients with monocytoid B-cell lymphoma is presented. The characteristic cell morphology, with homogeneous nuclei, low number of mitoses, and clear, wide cytoplasm, was present in both. Tumour cells expressed CD45, CD20, HLA-DR and monoclonal IgM-lambda and lambda chains, respectively. Case no. 1 had more irregular nuclei, protruding nucleoli, advanced stage at diagnosis and shorter clinical course. An epithelioid granulomatous reaction was present in case no. 2, which delayed the diagnosis until relapse. The diverse forms of clinical onset of monocytoid B-cell lymphoma, as well as its possibly aggressive course, association with other types of lymphoma and the difficulties for an adequate morphologic identification are commented.

Female↗

Drug-induced agranulocytosis: prognostic factors in a series of 168 episodes.

The prognostic value of 36 clinical and analytical parameters at diagnosis in patients with drug-induced agranulocytosis was analysed in an adult population. This multicentre, retrospective study examined possible prognostic factors by multiple logistic regression analysis in a series of 168 clinical episodes. The overall mortality was 16%. Renal insufficiency at diagnosis and the development of bacteraemia were associated with a poor prognosis. Advanced age, decreased leucocyte count, lymphocytopenia, bone marrow myeloid hypoplasia, increased percentage of bone marrow plasma cells and shock were found to be associated with a poor prognosis only in the univariate analysis. An independent analysis of the myeloid cellularity at diagnosis showed an inverse correlation with the time to recovery of the granulocyte counts (r = -0.43; P = 0.001). Our data indicate that despite some important clinical differences (higher incidence of infections of the oropharynx, shorter period of neutropenia and almost exclusive presence of gram-negative organisms), the infections complicating the treatment of cancer patients have the same prognostic features than those seen in patients with acute agranulocytosis. Therefore the established therapeutic guidelines for neutropenia after cancer chemotherapeutic agents are applicable to patients with acute agranulocytosis.

Acute Disease↗

Hb F-Catalonia or alpha 2G gamma(2)15(A12)Trp----Arg.

Hb F-Catalonia, a G gamma chain variant with a Trp----Arg substitution at position gamma 15(A12), was observed in two Spanish newborn babies from Northeastern Spain. Analyses were performed with different reversed phase high performance liquid chromatographic procedures that allowed the identification of the amino acid replacement in only a minute quantity of the isolated G gamma X chain.

Amino Acids↗

Low prostacyclin synthetase activity of fetal rat aorta. Progressive increase after birth.

Aortae from fetal or 3 weeks old rats produced very small amounts of PGI2, prostacyclin. This production increased from 4 weeks on, reaching adult values at about ten weeks. This maturation seemed to be predominantly determined by a change in the PGI2 synthetase system, rather than in arachidonic acid availability, phospholipase or cyclo-oxygenase activity. The anti-oxidant ascorbic acid stimulated prostacyclin production more strongly in adult than in young rat aortae. This finding suggests that the lower production of PGI2 by young tissues is not due to an enhanced inhibition of prostacyclin synthetase by lipid peroxides.

6-Ketoprostaglandin F1 alpha↗

Behavioral consequences of the hypotaurine-ethanol interaction.

In order to evaluate the effect of hypotaurine on ethanol-induced locomotion, different groups of mice received an injection of saline or 5.62, 8.45, 11.25, 16.87 or 33.75 mg/kg of hypotaurine 30 min prior to administering ethanol (2.4 g/kg). The duration of the effect of hypotaurine was explored by treating animals with ethanol 0, 30, 60 and 90 min after hypotaurine pretreatment. The effect of hypotaurine on acute stimulating ethanol locomotion was evaluated by pretreating animals with saline or 11.25 mg/kg of hypotaurine 30 or 60 min before ethanol (1.6, 2.4, 3.2 g/kg) or saline injections. Hypotaurine (11.25 mg/kg) required 30 min to boost, specifically ethanol-stimulated locomotion (2.4 g/kg). These results suggest a central locus for the interaction, firstly, because blood ethanol levels were not different between hypotaurine and saline pretreated mice, and, secondly, because a cotreatment with beta-alanine (22 mg/kg), a beta-amino acid that counteracts the transfer of hypotaurine across the blood-brain barrier (BBB), prevented the enhancement in ethanol-induced locomotion produced by hypotaurine.

Animals↗

[Presence of antibodies against Toxoplasma gondii in adolescents from the African continent].

It was determined the presence of antibodies anti-T. gondii in young, 13-16 year old, belonging to Republic Arab Saharaui; Popular Republic of Angola; Ethiopia and Republic of Ghana. From a total of 707 sera analyzed, the 71.43% of them showed the presence of specific antibodies. The prevalence of antibodies did not differ significantly (P > 0.05) between males and females in Angola and Republic Arab Saharaui. It was found a significant difference (P < 0.0001) among countries.

Adolescent↗