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Biomedical subjects

N Martín

Publications and source records attributed to N Martín.

At least 19 recordsLinked to original sources

[Acute leukemia in patients with Down syndrome].

BACKGROUND: Children with Down syndrome (DS) have a higher risk of acute leukemia than the remaining pediatric population. A favorable outcome of acute myeloid leukemia (AML) has recently been described in these patients whereas the prognosis of acute lymphoblastic leukemias (ALL) is similar to that in other children. The main cause of morbidity and mortality in children with Down syndrome are complications related to chemotherapy, leading to numerous modifications in treatment protocols. OBJECTIVES: To characterize acute leukemias in children with Down syndrome in our center and determine their clinical outcome. METHODS AND RESULTS: Between 1990 and 2002, 214 children were diagnosed with acute leukemia at the Niño Jesus Hospital (40 with AML and 174 with ALL). Of these, eight children (3.8 %) had Down syndrome. AML (2/40) represented 5 % of myeloid leukemias and ALL (6/174) represented 3.4 % of lymphoblastic leukemias. The most frequent complication was hematologic toxicity due to chemotherapy, causing a high incidence of infections: pneumonia (5/8) and bacteriemia (5/8). In all patients, these complications led to treatment interruption or dose reduction. Two children died from treatment-related toxicity. Of these, one with AML developed fulminant sepsis due to Candida infection and the other, diagnosed with high risk ALL, died from multiorgan failure after high doses of methotrexate and ARA-C. CONCLUSIONS: Patients with Down syndrome diagnosed with acute leukemia show a higher incidence of treatment-related complications, which affects their prognosis. Consequently, individualized treatment of these children in qualified units is essential.

Child↗

Electrospray ionisation and ion-trap fragmentation of substituted 3,4-dihydro-2(1H)-pyridin-2-ones.

A variety of 5-alkoxycarbonyl-4-aryl-6-methyl-3,4-dihydro-2(1H)-pyridones and hexahydrofuro[3,4-b]-2(1H)-pyridones have been investigated by electron impact (EI) and electrospray ionisation (ESI) techniques. Sequential product ion fragmentation (MS(n)) was performed to elucidate the degradation pathways for these compounds. Comparisons are made between positive and negative even-electron ions from ESI spectra and the molecular radical cations obtained under EI conditions. The data collected in this paper provide information on the strong impact that different substituents have on the ion fragmentation process.

Gas Chromatography-Mass Spectrometry↗

Tetrathiafulvalene derivatives as NLO-phores: synthesis, electrochemistry, Raman spectroscopy, theoretical calculations, and NLO properties of novel TTF-derived donor-pi-acceptor dyads.

Novel pi-conjugated donor-acceptor chromophores, based on the strong electron-donating tetrathiafulvalene moiety and different electron-withdrawing acceptors, exhibit large second-order optical nonlinearities. The effect of increasing the length of the polyenic spacer and the influence of the nature of the acceptor moiety on the NLO properties have been studied by using the electric field-induced second-harmonic generation (EFISH) technique as well as by semiempirical and ab initio theoretical calculations. A charge-transfer band has been observed in the absorption spectra of these D-pi-A compounds that undergoes an hypsochromic shift when increasing the number of vinylenic spacer units connecting both donor and acceptor moieties. The degree of the intramolecular charge transfer from the donor to the acceptor has also been analyzed by means of Raman spectroscopy.

Journal Article↗

Synthesis of photo- and electroactive stilbenoid dendrimers carrying dibutylamino peripheral groups.

[structure: see text]. A novel convergent synthetic route for the preparation of functionalized and fluorescent stilbenoid dendrons built on the 1,3,5-benzene core and endowed with a periphery of dibutylamino groups has been developed. Long alkyl chains have been incorporated on the peripheral amino moieties to increase the solubility of the final products. Good donor ability of the new dendrimers has been observed by cyclic voltammetry measurements as a result of the presence of the peripheral dibutylaniline moieties.

Journal Article↗

C(60)-based triads with improved electron-acceptor properties: pyrazolylpyrazolino[60]fullerenes.

A series of triad pyrazolylpyrazolino[60]fullerenes has been prepared in one pot from suitably functionalized hydrazones by 1,3-dipolar cycloaddition reactions under microwave irradiation. The electrochemical properties of the compounds obtained were investigated by cyclic voltammmetry, and they show better electron acceptor character than the parent C(60) in all cases. Fluorescence experiments and time-resolved transition spectroscopy indicate the existence of photoinduced charge-transfer processes with the C(60) triplet acting as the acceptor.

Journal Article↗

Reductive electrochemistry of spiromethanofullerenes.

The synthesis and electrochemical properties of spiromethanofullerenes 1-6 are described. The syntheses were achieved via the diazomethane route, and the regioisomeric distribution of bis-adducts 3 was determined by (1)H NMR, UV-vis, and HPLC analysis. The electrochemistry of these compounds in dichloromethane exhibits, besides several reversible reductions, some irreversible waves. Reductive electrolysis of 1 and 3-5 in dichloromethane leads to the removal of the addend and thus to the formation of C60. Reductive electrolysis of 1, 2 and 6 in dichloromethane leads to a different reaction, which we tentatively assign to a reaction with the solvent to form fullerene-CH2Cl products. Electrolyses in the less reactive solvent THF lead to adduct removal for 1 and 3-5. Interestingly, significant formation of bis-adducts from the corresponding monoadducts was observed for 4 and 5. These electrochemically induced reactions, namely addend removal, reaction with the solvent, and addend transfer are influenced by the structure of the addend and by the choice of solvent.

Journal Article↗

Mechanism of the addition reaction of alkyl azides to [60]fullerene and the subsequent N2 extrusion to form monoimino-[60]fullerenes.

The 1,3-dipolar cycloaddition of methyl azide to C60 and the subsequent nitrogen elimination from the formed triazoline intermediate to yield the aziridine adduct have been studied using semiempirical and density functional methods. The results obtained show that the addition of methyl azide to C60 takes place in the ring junction between two six-membered rings leading to a closed [6,6]-trizoline intermediate with an energy barrier of about 20 kcal mol-1 and an exothermicity of ca. 2 kcal mol-1 at the B3LYP/6-31G**//AM1 level of theory. The subsequent thermal loss of N2 takes place through a stepwise mechanism in which the cleavage of the N-N single bond precedes the breaking of the N-C bond, with a total activation energy of approximately 45 kcal mol-1. The N2 loss occurs simultaneously with the formation of the new N-C bond. During the process, the steric effects of the leaving N2 molecule prevent the addition of the nitrene substituent to the [6,6]-ring junction attacked initially and force the addition to an adjacent [5,6]-ring junction.

Journal Article↗

A study of the electrospray ionisation and ion-trap fragmentation of [M - H](-) ions of new 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazin-2-thiones.

The electrospray ionisation (ESI) in negative mode of the pharmacologically significant 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazin-2-thiones, and their subsequent fragmentations using an ion-trap mass spectrometer, have been investigated. Experiments on sequential product ion fragmentations (MS(n)) were performed in order to elucidate the degradation pathways for these compounds. The data presented show that the fragmentation of the even-electron [M - H](-) ions could proceed through an internal nucleophilic substitution displacement. Decarboxylation and extrusion of carbon disulfide are other fragmentations observed.

Decarboxylation↗

The distribution of two different vitamin D receptor polymorphisms (BsmI and start codon) in primary hyperparathyroidism.

INTRODUCTION: The bb genotype of the BsmI polymorphism of the vitamin D receptor (VDR) is more common in primary hyperparathyroidism (HPT) than in the general population in Swedish and German women. However, little is known about the association of HPT with the start codon polymorphism of the VDR (defined by FokI). OBJECTIVE: To study the distribution of the VDR genotypes in a group of women with HPT compared with a control group. The bone mineral density (BMD) of different genotypes was also investigated. METHODS: VDR alleles were typed by polymerase chain reaction (PCR) assay around the polymorphic BsmI or FokI restriction sites in 67 control women (48.5 +/- 10 years) and 53 women with HPT (61.4 +/- 11 years). They were all Caucasian and born in the Canary Islands. Lumbar and proximal femur BMDs were measured by dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). RESULTS: The 'bb' genotype was equally frequent in controls and HPT subjects (46.3 and 45.3%, respectively). There was a trend towards a lower prevalence of the FF genotype amongst women with HPT as compared with controls (41.5 vs. 57.1%; P = 0.09). BMD was lower in patients with HPT compared with controls in the lumbar spine and the proximal femur. CONCLUSIONS: The association of the BsmI polymorphism of the VDR gene with HPT is not applicable to all geographical areas. In Canarian postmenopausal women suffering from HPT, VDR genotype distribution is similar to that found in controls. A possible association of HPT with the FokI polymorphism deserves further investigation.

Aged↗

[Usefulness of molecular screening in childhood lymphoblastic leukemias].

PURPOSE: To demonstrate that a molecular screening by reverse transcriptase polymerase chain reaction (RT-PCR) of TEL/AML1, E2A/PBX1 and BCR/ABL genes in pediatric acute lymphoblastic leukaemia is a rapid method that allows one to exceed the percentage of adult patients with the BCR/ABL rearrangement. PATIENTS AND METHODS: 12 Spanish children with acute lymphoblastic leukaemia were studied, 11 of them newly diagnosed and 1 relapsed. The patients were between 18 months and 10 years old. Bone marrow aspiration was collected between april and december 1996, RNA was isolated and cDNA was subjected to PCR amplification for TEL/AML1, E2A/PBX1 and BCR/ABL genes. Normal ABL and E2A genes were studied as amplification controls. RESULTS: One of these hybrid genes was found in 33.3% of patients studied. TEL/AML1 in two cases (16.6%), E2A/PBX1 in one case (8.3%) and BCR/ABL in another one (8.3%). CONCLUSIONS: On the basis of these data it would be useful to achieve a molecular screening of TEL/AML1, E2A/PBX1 and BCR/ABL genes in pediatric acute lymphoblastic leukaemia for allowing a molecular classification in a great percentage of patients that exceed the BCR/ABL positivity in adults.

Aneuploidy↗

[A contagiousness study in 3071 familial contacts of tuberculosis patients].

BACKGROUND: The study of contacts of patients with tuberculosis is an important preventive measure which helps to identify the risk factors for contagion, to detect new cases of the disease early and to break the epidemiological chain of transmission. MATERIAL AND METHOD: Three thousand and seventy-one contacts of 635 patients with tuberculosis were studied in our department over a period of 6 years. With the aid of uni- and multivariate analyses we established the importance of different factors in the appearance of tuberculous disease and infection in contacts. RESULTS: There were 1,341 tuberculin positive contacts (44%). The proportion increased in relation to the degree of the relationship and the bacillary density of the index case. A hundred and seventy-six new cases of tuberculosis were diagnosed among the contacts (5.7%). To study the risk factors for contagion, we analyzed the characteristics of 322 patients with positive sputum smears and their 1,623 contacts; 124 new cases were diagnosed among them (124/176; 70%). The most important factors for contagion in the multivariate analysis were the closer relationship (odds ratio [OR] = 8.32; confidence interval [Cl] 95% = 3.9-17.6), greater TST reaction of contacts (OR = 4.43; Cl 95% = 2.5-7.7), presence of more than 10 bacilli per microscopic field in the sputum samples of the index case (OR = 1.97; Cl 95% = 1.1-3.3), male contacts (OR = 1.86; Cl 95% = 1.2-2.7) and those younger than 15 years (OR = 1.58; Cl 95% = 1.01-2.45). Conversely, the sex of the index case and the history of previous tuberculosis in contacts did not influence the contagion. CONCLUSIONS: The study of contacts offers a high yield in the diagnosis of new tuberculosis cases, because the incidence of the disease is much higher than that of the general population. Moreover, it allows the detection of newly infected subjects in whom the application of chemoprophylaxis prevents the development of the disease, and thus the epidemiologic chain of transmission is broken.

Adolescent↗

Involvement of calcium in the cardiac depressant actions of a garlic dialysate.

In order to elucidate a possible role for calcium on the negative cardiotropic effects of a garlic (Allium sativum L., Liliaceae) dialysate in rat atria we studied: (a) the effects of our extract 15 min after preincubation with high and low concentrations of extracellular calcium ([Ca2+]o) on left and right activity of rat atria. The negative inotropism of garlic dialysate increased with calcium 0.75 mM; in contrast, high level of calcium (4.5 mM) induced a significant reduction of this depressant effect. None of these treatments modified the negative chronotropism of garlic; (b) nifedipine (10(-9) to 10(-7) M, verapamil (10(-9) to 10(-7) M) and diltiazem (10(-9) to 10(-7) M) induced a concentration-dependent synergism of the log concentration-effect of garlic dialysate on left atria. Verapamil and diltiazem (10(-7)M), but not nifedipine increased the inhibitory chronotropism of garlic in right atria; (c) negative inotropic and chronotropic effects demonstrated by nifedipine (1 x 10(-10) to 1.1 x 10(-6) M) were antagonized as expected by preincubation with Bay K-8644. Depressant actions of garlic were not modified with this pretreatment. These results suggest that the negative inotropic effect of our garlic dialysate is related to [Ca2+]o availability. It is possible that a restriction of intracellular calcium contributes to this effect. However, the negative chronotropic effect of garlic is scarcely affected by these modifications.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Prediction of left ventricular mass changes after renal transplantation by polymorphism of the angiotensin-converting-enzyme gene.

Cardiac complications are the main cause of death in renal transplant patients and left ventricular hypertrophy (LVH) may play a determinant role. An association between the insertion-deletion polymorphism of the angiotensin-converting enzyme (ACE) gene and LVH has been reported in adults. However, little is known about the genetic influence on left ventricular mass changes after renal transplantation, where unique environmental factors, such as cyclosporine A (CsA) and prednisone treatment concur. In fact, CsA treatment has recently been associated with the development of LVH. We prospectively determined the changes on cardiac structure and function, assessed by echocardiographic criteria, in 38 consecutive nondiabetic adults who received a cadaveric renal allograft. They were treated with cyclosporine and prednisone and maintained a good renal function during the follow-up. Echocardiographic studies (M-mode, 2-B and color flow Doppler) were performed without previous knowledge of the genetic typing, at the time of transplantation, and 6 and 12 months later. ACE alleles were typed using a PCR-based assay developed to ascertain the presence of an insertion (I)-deletion (D) polymorphism in intron 16 of the ACE gene. Patients with the so-called "unfavorable" DD genotype (N = 16) were compared with the ID or II genotypes (N = 22). The baseline left ventricular mass index was similar in patients with or without the unfavorable DD genotype (X +/- SE; 166.6 +/- 10.4 vs. 181.3 +/- 9 g/m2, respectively) and a similar proportion fulfilled the criteria of LVH (88% vs. 82%, respectively). The mean percent increase of the left ventricular mass index 12 months after renal transplantation was significantly higher in patients with the DD genotype compared to those with other genotypes (21.3 +/- 7.9 vs. -0.08 +/- 4.9%, respectively; P < 0.05). As a result, 94% of DD patients showed LVH at the end of the follow-up, while 68% of the ID or II patients had LVH (P < 0.05). In addition, the left ventricular ejection fraction significantly increased only in ID or II patients 12 months after transplantation with respect to baseline (ID/II patients, 70.4 +/- 1.5 vs. 63.7 +/- 1.8%; P < 0.05; DD patients, 68.3 +/- 2.1 vs. 63.3 +/- 2.9%). The deleterious effect of the DD genotype was independent of blood pressure, biochemical parameters, weight gain, and cumulative steroids dosages or cyclosporine levels. In conclusion, genetic factors determine the changes on cardiac structure and function after renal transplantation. The presence of the DD genotype of the ACE gene is a marker associated with an elevated risk of LVH in this population.

Adult↗

Influence of vitamin D receptor genotype on bone mass changes after renal transplantation.

Renal transplant patients immunosuppressed with cyclosporine A (CsA) exhibit both a significant bone loss and an increased rate of bone fractures. An association between common allelic variants of the the vitamin D receptor (VDR) gene and bone mineral density and turnover has been reported in adults. However, the genetic influence on the rate of bone loss after renal transplantation has not been explored. We prospectively determined the changes in spinal mineral density in 34 consecutive nondiabetic adults who received a cadaveric renal allograft. Serum biochemical markers of bone metabolism and the vertebral mineral density (VMD) assessed by quantitative computed tomography were determined at the time of transplantation and three and twelve months later. In fifteen patients the histomorphometric features of iliac bone were analyzed at baseline and twelve months after transplantation. VDR alleles were typed by a PCR assay based on a polymorphic BsmI restriction site. Patients with the so-called "favorable" bb genotype (N = 12) were compared with those with the Bb or BB genotype (N = 22). Baseline VMD was similar in patients with or without the favorable bb genotype. Three months after transplantation the mean (+/- SD) VMD decreased 14 +/- 13.3 percent in all patients (16.5 +/- 13.1% in patients homozygous for the b allele and 13.77 +/- 13.9% in those with Bb or BB genotypes). The rate of VMD loss at this time inversely correlated with pretransplant PTH levels (r = -0.40; P < 0.05). Between 3 and 12 months after transplantation, patients with the favorable bb genotype recovered more VMD than those with Bb or BB types and showed a significantly higher Z score at the end of the follow-up (-0.37 +/- 1.16 vs. -1.10 +/- 1.20, respectively; P < 0.05). The beneficial effect of bb genotype was independent of the prevailing PTH levels and was also observed in those patients with a baseline PTH level < 250 pg/ml (final Z score: bb, -0.42 +/- 1.3, N = 11; Bb/BB, -1.35 +/- 0.8, N = 11, P < 0.05). At the end of follow-up, the histomorphometric studies showed a higher bone formation rate adjusted for PTH levels in patients with the Bb or BB genotype than in those with the favorable bb genotype (0.29 +/- 0.06 vs. 0.21 +/- 0.08 micron3/micron2/day respectively; P < 0.05). In conclusion, high pretransplant PTH levels enhance the early trabecular bone loss after renal transplantation, and functionally different alleles of the vitamin D receptor gene may condition the bone turnover and the degree of recovery of the bone mass.

Adult↗