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Biomedical subjects

A León

Publications and source records attributed to A León.

At least 19 recordsLinked to original sources

The results of consolidation with autologous stem-cell transplantation in patients with peripheral T-cell lymphoma (PTCL) in first complete remission: the Spanish Lymphoma and Autologous Transplantation Group experience.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas associated with poor prognosis with standard chemotherapy. Consolidation with autologous stem-cell transplantation (ASCT) may improve survival. We present 74 patients transplanted in first complete response (CR) from the Spanish Lymphoma and Autologous Transplantation Group cooperative group. PATIENTS AND METHODS: Median age was 46 years. Eighty-eight percent presented advanced (III-IV) Ann Arbor stage; 53% had B symptoms; 52% had high lactate dehydrogenase; 65% had two or three risk factors of the adjusted-International Prognostic Index; 58% presented a high Tumor score and in 14% more than two adverse factors of the Prognostic Index for peripheral T-cell lymphoma (PIT) were observed. RESULTS: With a median follow-up of 67 months from diagnosis, the 5-year overall survival (OS) was 68% and progression-free survival (PFS) reached 63%. The multivariate analysis showed that the only factor associated with a shorter OS and PFS was the presence of more than two risk factors from the PIT risk system. CONCLUSIONS: In a retrospective study with a prolonged follow-up, consolidation with ASCT in CR patients who had presented unfavorable prognostic factors at diagnosis substantially increased the OS and PFS when compared with conventional chemotherapy. The PIT risk system identified 14% of patients without benefit from ASCT consolidation. Thus, other innovative therapies are still necessary in certain cases.

Adolescent↗

Design and evaluation of "3 + 1" mixed ligand oxorhenium and oxotechnetium complexes bearing a nitroaromatic group with potential application in nuclear medicine oncology.

The synthesis and evaluation of a series of oxotechnetium and oxorhenium complexes containing a nitroaromatic moiety as potential radiopharmaceuticals for targeting tumour hypoxia is presented. 99mTc labelling was performed in high yield (>85%) and radiochemical purity (>90%). Their structure was corroborated by means of the rhenium complexes. Reduction potentials were in the range for bioreducible compounds. 99mTc complexes III-VI were selected for "in vivo" experiments in view of the results of cytotoxicity studies. Biodistribution in normal animals was characterized by high initial blood, lung and liver uptake, fast blood and soft tissue depuration and preferential excretion via the hepatobiliary system. Initial tumour uptake was moderate but tumour/muscle ratios for complexes III and IV, were favourable at all time points. Although the results are encouraging further development is still necessary in order to achieve higher tumour uptake and lower gastrointestinal activity.

Animals↗

Model based on a quantum algorithm to study the evolution of an epidemics.

A model based on a quantum algorithm is used to study the spread of HIV virus and to predict infection rates on individuals who are not aware of their particular condition. The model makes an analogy between quantum systems and individuals who are infected by the disease. Individuals are represented by two-level quantum systems (quantum "bit"), and the interactions among individuals who cause the infection are represented by unitary transformations. The population is divided into categories according to their behaviour, and the interactions among those individuals in the same category and those in different categories are simulated. The objective is to obtain statistical data on the number of infected individuals depending on the time for every category and for the entire population. Besides, we analyse the impact of the evolution of the disease on individuals who have not knowledge of their specific sanitary condition.

Algorithms↗

Fixed dose-rate infusion of gemcitabine in combination with cisplatin and UFT in advanced carcinoma of the pancreas.

BACKGROUND: Gemcitabine is currently considered the standard treatment for advanced pancreatic cancer (APC). Cisplatin and a fluoropyrimidine have some activity in the treatment of this cancer. The aim of this trial is to evaluate the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated with cisplatin and UFT in patients with APC. PATIENTS AND METHODS: Forty-six chemotherapy-naïve patients with APC that was either unresectable or metastatic were included in this phase II study. All of them had Karnofsky performance status > or =50 and unidimensionally measurable disease. Treatment consisted of gemcitabine 1,200 mg/m2 given as a 120-min infusion weekly for three consecutive weeks, cisplatin 50 mg/m2 on day 1 and oral UFT 400 mg/m2/day (in two to three daily doses) on days 1 to 21; cycles of treatment were given every 28 days. RESULTS: A total of 208 cycles of chemotherapy were given with a median of 4 per patient. Fourteen patients (30%) achieved partial responses (95% CI 19-48%) and 17 (37%) had stable disease. The median time to progression was 5 months, and the median overall survival 9 months. Nineteen patients (49%; 95% CI 32-64%) had a clinical benefit response. Grade 3-4 WHO toxicities were as follows: neutropaenia in 26 patients (57%), with 5 cases of febrile neutropaenia (11%), thrombocytopaenia in 15 (33%), anaemia in six (13%), diarrhoea in 5 (11%), asthenia in 2 (4%) and mucositis in 1 (2%). Seven patients required hospitalisation for treatment-related complications. CONCLUSION: A fixed dose-rate infusion of gemcitabine associated with cisplatin and UFT is active in patients with APC, though at the cost of considerable toxicity.

Adult↗

HLA class II and response to interferon-beta in multiple sclerosis.

OBJECTIVE: To study the relationship between human leucocyte antigen (HLA) genotype and clinical response to interferon-beta (IFN-beta). METHODS: We analysed the HLA class II genotypes of 96 multiple sclerosis (MS) patients treated with IFN-beta. The patients were classified as responders or non-responders according to clinical criteria: one or more relapses or a sustained increase after 1 year treatment compared with the year prior to IFN-beta therapy of > or = 0.5 points on the Expanded Disability Status Scale (EDSS). RESULTS: There were 66 (69%) responders and 30 (31%) non-responders. Baseline clinical characteristics were similar. We found no association between HLA class II alleles and clinical response to IFN-beta. CONCLUSIONS: HLA genotype does not appear to influence the clinical response to IFN-beta in MS patients.

Adult↗

Monte Carlo evaluation of kerma in an HDR brachytherapy bunker.

In recent years, the use of high dose rate (HDR) after-loader machines has greatly increased due to the shift from traditional Cs-137/Ir-192 low dose rate (LDR) to HDR brachytherapy. The method used to calculate the required concrete and, where appropriate, lead shielding in the door is based on analytical methods provided by documents published by the ICRP, the IAEA and the NCRP. The purpose of this study is to perform a more realistic kerma evaluation at the entrance maze door of an HDR bunker using the Monte Carlo code GEANT4. The Monte Carlo results were validated experimentally. The spectrum at the maze entrance door, obtained with Monte Carlo, has an average energy of about 110 keV, maintaining a similar value along the length of the maze. The comparison of results from the aforementioned values with the Monte Carlo ones shows that results obtained using the albedo coefficient from the ICRP document more closely match those given by the Monte Carlo method, although the maximum value given by MC calculations is 30% greater.

Brachytherapy↗

DQB1*0602 allele shows a strong association with multiple sclerosis in patients in Malaga, Spain.

BACKGROUND: The human leukocyte antigen (HLA) class II DR2 haplotype (DRB1*1501, DQA1*0102, DQB1*0602) has been associated with multiple sclerosis (MS) in all ethnic groups and very strongly in Caucasians. AIM: To investigate the possible HLA class II (DRB1, DQA1 and DQB1) associations with MS in Malaga, southern Spain. METHODS: We analysed the HLA class II sub-regions DRB1, DQA1 and DQB1 by polymerase chain reaction (PCR) and sequence-specific oligonucleotide probe hybridization (PCR/SSO) for DRB1 and DQB1 and with sequence-specific primers (PCR/SSP) for DRB1 subtypes and DQA1. Possible HLA class II associations with clinical MS characteristics were investigated in 149 subjects with and 160 without MS. RESULTS: Associations were detected between MS and the HLA class II alleles DRB1*1501 (45.6 % vs. 21.3%, p=0.001), DQA1*0102 (44% vs. 29.4%, p=0.001) and DQB1*0602 (45% vs. 20.6%, p=0.001). The DR2 haplotype (DRB1*1501, DQA1*0102, DQB1*0602) was associated with MS (43.6 % vs. 20%, p=0.002). DQB1*0602 was the only allele that maintained an association with MS in a logistic regression model. No HLA class II alleles or genotypes were significantly associated with any clinical characteristics of MS. CONCLUSIONS: Our results confirm the positive association of the DR2 haplotype with MS, particularly the allele DQB1*0602, in the population studied. DR4 was not associated with the disease in Malaga. HLA class II alleles or haplotypes were not associated with clinical or demographic characteristics, or clinical form or severity of MS.

Adolescent↗

Elderly age and prior autologous transplantation have a deleterious effect on survival following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results from the Spanish multicenter prospective trial.

Over a 3-year period, 145 patients ineligible for myeloablative conditioning underwent reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (SCT) from an HLA-identical sibling in a prospective study. The median age was 54 years, 88 patients were male and 61 patients were beyond the early-intermediate phase of their disease. The 100-day probability of developing grade II-IV acute graft-versus-host disease (GVHD) was 34%, and the 1-year probability of developing chronic extensive GVHD was 41%. The 1-year probabilities of transplant-related mortality (TRM), overall (OS) and progression-free survival were 20, 60 and 52%, respectively. Multivariate analyses found a better OS in: (i) patients <60 years; and (ii) recipients of a first SCT; and a higher TRM in: (i) age >60 years, (ii) recipients of a prior autologous SCT, and (iii) an ECOG performance status >1. The 1-year TRM in patients with 0 or 1 and >2 of the above-mentioned adverse prognostic factors were 17 vs 53%, respectively (P<0.001). In summary, our study shows that elderly patients have a higher TRM following an RIC protocol. However, age by itself should not preclude these RIC transplants, since TRM appears to be unacceptably high only in the presence of additional adverse factors.

Acute Disease↗

Biweekly docetaxel and gemcitabine as neoadjuvant chemotherapy in stage II and III breast cancer patients: preliminary results of a phase II and pharmacogenomic study.

The purpose of this study is to evaluate the efficacy and safety of a biweekly neoadjuvant docetaxel/gemcitabine regimen in patients with histologically confirmed stage II and III breast cancer. In addition, a cDNA microarray study attempted to correlate pretreatment gene-expression profile with clinical and pathologic responses. Docetaxel 65 mg/m(2) was given in a 60-minute intravenous infusion followed by gemcitabine 2,500 mg/m(2) in a 30-minute intravenous infusion every 2 weeks for six cycles; prophylaxis with growth factors was allowed. Four cycles of standard AC (doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)every 21 days) was routinely delivered to all patients postsurgery. Thirty patients are accrued on-study so far. The overall response rate for 24 evaluable patients was 79% (95% confidence interval, 9.7 to 53.5) with six complete responses and 13 partial responses. One patient (4%) out of 23 achieved a pathologic complete response in the breast at the time of definitive surgery. Breast conservation procedure was possible in 14 patients (61%). A total of 161 cycles has been delivered. Grade 1/2 alopecia and a mild grade 1/2 LDH increase were the most frequently reported adverse events (78% and 55% of cycles, respectively). Grade 3/4 neutropenia was reported in 18 cycles (11%). These preliminary results show that biweekly docetaxel and gemcitabine is an optimal regimen as neoadjuvant treatment of stage II and III breast cancer. In spite of the large tumor size, breast conservation was possible in 61% of the patients. In general, toxicity was very manageable.

Adult↗

Detection and characterization of cyclodextrin complexes with beta-carboline derivatives by spectroscopic techniques.

beta-Carboline alkaloids exhibit a great variety of pharmacological activities. The solid inclusion complexes of harmane and harmine with beta-cyclodextrin and also with hydroxypropyl-beta-cyclodextrin, have been prepared following different procedures. IR and NMR spectroscopies were employed to verify the interaction of the guest molecules with the cyclodextrin cavities. The differences observed in the IR and NMR spectra are in agreement with those described in the literature for other guest molecules. The shifts in the 13C- and 1H-NMR spectra confirm the existence of the inclusion complexes. The fluorescence emission spectra of these complexes dissolved in buffered aqueous solution (pH 7.3) exhibit the characteristic peaks of the cationic form for harmane alkaloids. The neutral bands are not present for the free alkaloids in aqueous solutions. Fluorescence quenching emission of the complexes is compared to that of the corresponding free alkaloids.

Carbolines↗

Autologous stem cell transplantation for primary refractory Hodgkin's disease: results and clinical variables affecting outcome.

BACKGROUND: Patients with primary refractory Hodgkin's disease (PR-HD) have a dismal prognosis when treated with conventional salvage chemotherapy. We analyzed time to treatment failure (TTF), overall survival (OS) and clinical variables influencing the outcome in patients undergoing autologous stem cell transplantation (ASCT) for PR-HD and reported to the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL/TAMO). PATIENTS AND METHODS: Sixty-two patients, 41 males and 21 females with a median age of 27 years (range 13-55) were analyzed. Forty-two patients (68%) had advanced stage at diagnosis, 47 (76%) presented with B symptoms and 29 (47%) with a bulky mediastinal mass. Seventy-five percent of the patients had received more than one line of therapy before ASCT. Thirty-three patients received bone marrow as a source of hematopoietic progenitors, and 29 peripheral blood. Six patients were conditioned with high-dose chemotherapy plus total-body irradiation and 56 received chemotherapy-based protocols. RESULTS: One-year transplantation-related mortality was 14% [95% confidence interval (CI) 6% to 23%]. Response rate at 3 months after ASCT was 52% [complete remission in 21 patients (34%), partial remission in 11 patients (18%)]. Actuarial 5-year TTF and OS were 15% (95% CI 5% to 24%) and 26% (95% CI 13% to 39%), respectively. The presence of B symptoms at ASCT was the only adverse prognostic factor significantly influencing TTF [relative risk (RR) 1.75, 95% CI 0.92-3.35, P = 0.08]. The presence of B symptoms at diagnosis (RR 2.08, 95% CI 0.90-4.79, P = 0.08), MOPP-like regimens as first-line therapy (RR 3.84, 95% CI 1.69-9.09, P = 0.001), bulky disease at ASCT (RR 2.79, 95% CI 0.29-6.03, P = 0.009) and two or more lines of therapy before ASCT (RR 2.24, 95% CI 0.95-5.27, P = 0.06) adversely influenced OS. CONCLUSIONS: In our experience, although overall results of ASCT in PR-HD patients are poor, one-quarter of the patients remain alive at 5 years. Despite this, other therapeutic strategies should be investigated in this group of patients to improve the outcome.

Adolescent↗

High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience.

BACKGROUND: T-cell immunophenotype constitutes an unfavorable prognostic factor in aggressive non-Hodgkin's lymphomas. High-dose chemotherapy with autologous stem-cell rescue (HDC/ASCT) is the best salvage therapy for patients with aggressive B-cell lymphomas. However, results with this therapy in peripheral T-cell lymphoma (PTCL) are not well defined. PATIENTS AND METHODS: From January 1990 to December 1999, 115 patients with PTCL underwent HDC/ASCT inside the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL-TAMO) registry. At diagnosis the median age was 41 years and 60% of patients presented with two or three risk factors from the adjusted International Prognostic Index (a-IPI). Thirty-two per cent of patients were transplanted in first complete response (CR), 62% in chemosensitive disease and 5% in refractory disease. RESULTS: Eighty-six per cent of the patients attained a CR and 5% a partial response (PR). With a median follow-up of 37 months (range 1-133), overall survival (OS), time-to-treatment failure (TTF) and disease-free survival (DFS) at 5 years was 56%, 51% and 60%, respectively; for the 37 patients transplanted in first CR, OS and DFS at 5 years were 80% and 79%, respectively. Lactase dehydrogenase (LDH), a-IPI and disease status pre-transplant were associated with outcome. CONCLUSIONS: More than half of patients with chemosensitive disease who were transplanted are expected to be alive at 5 years. We confirm the utility of the pre-transplant IPI system in predicting outcome. Salvage treatment results with HDC/ASCT in PTCL are similar to those found in corresponding aggressive B-cell lymphomas.

Adolescent↗

Early age thermal conditioning immediately reduces body temperature of broiler chicks in a tropical environment.

Early age thermal conditioning (TC) durably improves resistance of broilers to heat stress and reduces body temperature (Tb). Three experiments on broiler chicks were conducted to evaluate the effects of TC at 5 d of age on Tb variation measured by thermometer between 4 and 7 d of age, under a tropical environment. Because manipulation of chickens to measure Tb with a thermometer may increase Tb, a preliminary experiment on 13 3-to-4-wk-old male broilers compared Tb measured by telemetry to Tb measured in the terminal colon during three successive periods at 22, 33, and 22 degrees C. During heat exposure, Tb rapidly increased by 0.9 degrees C and plateaued over 24 h. During the last period, seven of the broilers rapidly reduced Tb to a plateau lower than the initial Tb, although six broilers exhibited more variable Tb. Measurement by thermometer underestimated on average core Tb by 0.28 degrees C at 22 degrees C and by 0.57 degrees C at 33 degrees C, whereas Tb recorded by telemetry was not affected by manipulation of the chickens. TC reduced Tb 24 h later in the three experiments. Compared to unexposed control chicks (N), 12 h of TC at 40 degrees C did not significantly reduce Tb at 7 d of age, although 24 h did. TC at 38 and 40 degrees C over 24 h significantly reduced Tb variation from 4 to 7 d of age compared to N chicks, whereas 36 degrees C did not. Withdrawing feed from the chicks for 2 h prior to measurement did not significantly reduce Tb at 4 and 7 d of age, but Tb reduction due to TC was greater in fed chicks (0.28 degrees C) than in chicks without feed (0.05 degrees C). Early age thermal conditioning at 38 to 40 degrees C at 5 d of age for 24 h reduced body temperature of 7-d-old male broilers.

Adaptation, Physiological↗

Relationship between cyanogenic compounds in kernels, leaves, and roots of sweet and bitter kernelled almonds.

The relationship between the levels of cyanogenic compounds (amygdalin and prunasin) in kernels, leaves, and roots of 5 sweet-, 5 slightly bitter-, and 5 bitter-kernelled almond trees was determined. Variability was observed among the genotypes for these compounds. Prunasin was found only in the vegetative part (roots and leaves) for all genotypes tested. Amygdalin was detected only in the kernels, mainly in bitter genotypes. In general, bitter-kernelled genotypes had higher levels of prunasin in their roots than nonbitter ones, but the correlation between cyanogenic compounds in the different parts of plants was not high. While prunasin seems to be present in most almond roots (with a variable concentration) only bitter-kernelled genotypes are able to transform it into amygdalin in the kernel. Breeding for prunasin-based resistance to the buprestid beetle Capnodis tenebrionis L. is discussed.

Amygdalin↗

[Pure red cell aplasia in a lung transplant patient].

Aplastic anemia secondary to infection by parvovirus B19 is normally an extremely rare problem in patients with no prior history. However, the presence of certain risks, such as receiving chronic immunosuppressant therapy, may facilitate its appearance. Very few cases have been published concerning red cell aplasia due to parvovirus B19 infection in patients receiving a transplanted lung. We report the case of a 24-year-old woman with cystic fibrosis who had received a double lung transplant. The patient developed red cell aplasia secondary to parvovirus B19 infection; severe anemia requiring multiple transfusions. Five days of intravenous immunoglobulin therapy resolved the anemia. We discuss the difficulty of serological diagnosis in such cases, the importance of using techniques that identify the virus and taking measures that may prevent recurrence.

Adult↗

Novel mixed ligand technetium complexes as 5-HT1A receptor imaging agents.

The synthesis, characterization and biological evaluation of two novel 3 + 1 mixed ligand 99mTc-complexes, bearing the 1-(2-methoxyphenylpiperazine) moiety, a fragment of the true 5-HT1A antagonist WAY 100635, is reported. Complexes at tracer level 99mTcO[(CH3CH2)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N(CH2CH2)2NCH2CH2S], 99mTc-1, and 99mTcO[((CH3)2CH)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N (CH2CH2)2NCH2CH2S], 99mTc-2, were prepared using 99mTc-glucoheptonate as precursor. For structural characterization, the analogous oxorhenium complexes, Re-1 and Re-2, were prepared by ligand exchange reaction using ReOCl3(PPh3)2 as precursor, and characterized by elemental analysis and spectroscopic methods. Complex Re-1 was further characterized by crystallographic analysis. Labeling was performed with high yield (>85%) and radiochemical purity (>90%) using very low ligand concentration. The structure of 99mTc complexes was established by comparative HPLC using the well-characterized oxorhenium analogues as references. In vitro binding assays demonstrated the affinity of these complexes for 5-HT1A receptors (IC50 : 67 and 45 nM for Re-1 and Re-2 respectively). Biological studies in mice showed the ability of 99mTc-1 and 99mTc-2 complexes to cross the intact blood-brain barrier (1.4 and 0.9% dose/g, respectively at 1 min post-inj.). The distribution of these complexes in various regions in rat brain is inhomogeneous. The highest ratio between areas reach and poor in 5-HT1A receptors was calculated for complex Tc-1 at 60 min p.i. (hippocampus/cerebellum = 1.7).

Animals↗