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Biomedical subjects

Javier Rodríguez

Publications and source records attributed to Javier Rodríguez.

13 recordsLinked to original sources
PubMed2007

Polymorphisms in the thymidylate synthase and dihydropyrimidine dehydrogenase genes predict response and toxicity to capecitabine-raltitrexed in colorectal cancer.

Pharmacogenetics is an increasingly useful field where the genetic studies are becoming an important tool for predicting drug toxicity and/or efficacy. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene polymorphisms could be highly informative tools in the clinical handling of colorectal cancer patients, who are following fluoropyrimidine based chemotherapy. Fifty-eight patients, with non-resectable metastatic colorectal cancer, were treated with capecitabine and raltitrexed, every three weeks. Patients were divided in a good-response group (complete and partial response) and a poor-response group (stable and progression). A genotype panel TS-DPD was evaluated. Results show that TS genotype analysis clearly differentiates patients with a worst response to a 5-fluorouracil based chemotherapy. DPD genotype was shown to be highly informative for prediction of toxicity of the treatment. These polymorphisms could represent an accurate, rapid and effective determination panel, indicative of resistance and toxicity for patients undergoing fluoropyrimidine based treatment.

Antimetabolites, Antineoplastic↗
PubMed2006

A volumetric model for growth of arterial walls with arbitrary geometry and loads.

Stress and deformation in arterial wall tissue are factors which may influence significantly its response and evolution. In this work we develop models based on nonlinear elasticity and finite element numerical solutions for the mechanical behaviour and the remodelling of the soft tissue of arteries, including anisotropy induced by the presence of collagen fibres. Remodelling and growth in particular constitute important features in order to interpret stenosis and atherosclerosis. The main object of this work is to model accurately volumetric growth, induced by fluid shear stress in the intima and local wall stress in arteries with patient-specific geometry and loads. The model is implemented in a nonlinear finite element setting which may be applied to realistic 3D geometries obtained from in vivo measurements. The capabilities of this method are demonstrated in several examples. Firstly a stenotic process on an idealised geometry induced by a non-uniform shear stress distribution is considered. Following the growth of a right coronary artery from an in vivo reconstructed geometry is presented. Finally, experimental measurements for growth under hypertension for rat carotid arteries are modelled.

Animals↗
PubMed2006

[Influence of shear stress on in-stent restenosis: in vivo study using 3D reconstruction and computational fluid dynamics].

INTRODUCTION AND OBJECTIVES: Local factors may influence neointimal proliferation following conventional stent implantation. In this study, the relationship between wall shear stress and luminal loss after coronary stenting was assessed using a combination of angiography, intravascular ultrasound, and computational fluid dynamics. PATIENTS AND METHOD: Seven patients with de novo right coronary lesions treated with conventional (i.e., bare metal) stents were included. Realistic three-dimensional geometric reconstructions were generated offline from angiographic and intravascular ultrasound data both immediately after stenting and at 6-month follow-up. A finite-volume model was used to calculate local wall shear stress within the stent and 4 mm proximally and distally to the stent. The mean coronary ostium entry flow velocity was assumed to be 25 cm/s in all cases. RESULTS: The mean neointimal thickness was 0.29 (0.21) mm. In five cases, weak negative correlations between wall shear stress and neointimal thickness were found: maximum r value = -0.34, minimum r value = -0.11 (P < .001). The neointimal thickness in segments in which the level of wall shear stress was in the lowest quartile was greater than that in segments in which it was in highest quartile, at 0.34 (0.21) mm and 0.27 (0.24) mm (P < .001) for quartiles 1 and 4, respectively. CONCLUSIONS: Low wall shear stress after stenting favors neointimal proliferation both within the stent and at the stent's edges.

Adult↗
PubMed2005

Spinal hydatidosis.

STUDY DESIGN: Retrospective study. OBJECTIVES: To revise the treatment of spinal hydatidosis. SUMMARY OF BACKGROUND DATA: About 50% of cases of bone hydatidosis are spinal. METHODS: Twenty patients with spinal hydatidosis were treated. There were 13 men and 7 women, with a mean age of 53.1 years. The median follow-up was 4.8 years. The infected area was the cervical spine in 1 patient, the dorsal spine in 7, the lumbar spine in 7, and the sacrum in 5. Curettage and resection of the infected bone were performed. The spine was exposed posteriorly in all but 2 patients. An additional posterior decompression and fusion with instrumentation were performed after removing the involved posterior elements in 8 patients. An anterior approach was used in 2 patients: a total corpectomy was performed and a bone graft was added. Two weeks later, a posterior decompression and fixation with instrumentation was done. No preoperative drugs were used. Medical antihelmintic treatment was used after surgery in all but 8 patients. RESULTS: Thirteen patients had spinal cord injury at the moment of surgery. The neurologic damage recovered only in 1 case. Repeated curettage was necessary in 13 cases: in 12 of them because of recurrence and in 1 because of surgical wound infection. In 6 cases of recurrence, there was also chronic wound infection. At last follow-up, 17 patients were free of disease. CONCLUSIONS: The treatment of choice of spinal hydatidosis is surgical removal of the affected vertebrae combined with posterior stabilization, followed by postoperative adjuvant chemotherapy. Recurrence is very frequent.

Adult↗
PubMed2003

Prevalence of PD and other types of parkinsonism in three elderly populations of central Spain.

The prevalence of Parkinson's disease (PD) and other types of parkinsonism in three elderly populations of central Spain was investigated using a door-to-door, two-phase approach. This design called for the administration of a brief questionnaire to subjects 65 years of age or older taken from the census of one urban municipality of Greater Madrid (Margaritas, Getafe), one rural site (Arévalo County, Avila), and one urban district of Madrid (Lista) in Spain (N = 5,278). Study neurologists extensively investigated those subjects who screened positively. The diagnoses, based on specified criteria, were reviewed to increase reliability across neurologists. We found 118 subjects with parkinsonism: 81 affected by PD (68.6%), 26 drug-induced parkinsonism (22.0%), 6 parkinsonism in dementia (5.1%), 3 vascular parkinsonism (2.5%), and 2 unspecified parkinsonism (1.7%). The prevalence was 2.2% (95% confidence interval [CI], 1.8-2.6) for all types of parkinsonism and 1.5% (95% CI, 1.2-1.8) for PD. The prevalence estimates of parkinsonism and PD increased with age, declining at 85 years and over. Age prevalence ratios were higher for men. Twenty-three subjects (28.4%) of the subjects with PD were detected through the screening and had not been diagnosed previously. Overall prevalence estimates of PD and other types of parkinsonism in central Spain rank at levels similar to those recently reported for other European and non-European elderly populations. Despite improvement in access to health services, an important proportion of PD patients may never seek neurological attention.

Aged↗
PubMed2003

[Long-term prognostic value of troponin I in patients admitted to a coronary unit for unstable angina].

INTRODUCTION AND OBJECTIVES: Troponin I (TnI) is a useful marker of myocardial damage for the diagnosis and prognosis of acute coronary syndrome. The purpose of this study was to analyze the long-term prognostic value of the peak TnI concentration obtained within 48 h of admission to the coronary unit for unstable angina. METHODS: The study included 149 consecutive patients. Serial determinations were made of the MB fraction of creatine kinase (CK-MB) and TnI. Patients without CK-MB elevation were classified into two groups depending on the presence of high (n = 58) or normal (n = 91) troponin I values. We prospectively analyzed the clinical and evolutive factors related to the probability of death, new acute coronary event, or coronary revascularization at one-year of follow-up. RESULTS: There were no differences in the clinical characteristics between groups, except that patients in the group with high TnI values were older (69 vs. 64 years, p = 0.01). At one year of follow-up there were no differences in the incidence of new acute coronary events or coronary revascularization procedures; however there was a higher mortality in the group with high TnI (13 vs. 4%; p = 0.01). The independent predictors of mortality were prior myocardial infarction (RR = 3), elevated troponin I (RR = 3.2), left ventricular ejection fraction < 35% (RR = 10), and age > 70 years (RR = 15). CONCLUSIONS: In patients with unstable angina a high troponin I value in the first 48 h of admission was associated with a higher mortality rate at one-year of follow-up.

Adult↗
PubMed2003

Cloning and characterization of the Leishmania (Viannia) braziliensis Hsp70 gene. Diagnostic use of the C-terminal fragment rLb70(513-663).

Cross-reactions between Leishmania braziliensis and Trypanosoma cruzi caused by common antigenic determinants hinder the specific diagnosis of cutaneous and mucocutaneous leishmaniasis (CL and MCL). Therefore, the usefulness of the 70-kDa heat shock protein (Hsp70) from L. braziliensis for differential serodiagnosis was investigated. The single-copy gene encoding Hsp70, consisting of 663 amino acids, was isolated from a genomic DNA library. The antigenicity data show that Hsp70 is an immunodominant antigen highly recognized (84%) by sera of patients with CL and MCL and to a lesser extent by chagasic patients (18.75%). Antigenic mapping of the 5 overlapping fragments into which the protein was split showed that the main antigenic determinants are located in the carboxy-terminal end. The linear antigenic determinants that show cross-reactions with chagasic sera are located in the fragment rLb70(352-518). The carboxy-terminal fragment rLb70(513-663) presents 70% sensitivity and 100% specificity, so it could be a potential candidate for specific serodiagnosis of CL and MCL caused by L. braziliensis.

Amino Acid Sequence↗
PubMed2002

Docetaxel plus vinorelbine as salvage chemotherapy in advanced breast cancer: a phase II study.

PRECIS: Administration of a combined regimen of docetaxel plus vinorelbine every 4 weeks is feasible and shows activity in heavily pretreated patients with advanced breast cancer. PURPOSE: To determine the activity and tolerance of docetaxel plus vinorelbine in heavily pretreated patients with advanced breast cancer. METHODS: Thirty-five metastatic breast cancer patients with ECOG performance status of 0-2 received docetaxel (80 mg/m2 given intravenously) on day 1 and vinorelbine (30 mg/m2 given intravenously) on days 1 and 14, every 4 weeks. The median number of prior chemotherapy regimens was 2 (range: 1-4). Twenty-five patients (71.4%) had been treated previously using intensive therapy approaches with peripheral blood-derived stem cell (PBSC) support, including high-dose chemotherapy (11 patients), multicyclic dose-intensive chemotherapy supported with repeated PBSC infusions (seven patients), or both (seven patients). Twenty-eight patients (80%) received previous chemotherapy for metastatic disease. Adjuvant therapy in the remaining seven patients consisted of high-dose chemotherapy and PBSC support or an anthracycline-containing regimen. RESULTS: The total number of courses was 229, and the median number of courses per patient was 6 (range: 1-16). There was one toxic death (2.8%). Grade 3-4 toxicities included mucositis (17.1%), neutropenia (37.1%), anemia (5.7%), vomiting (2.9%), and asthenia (14.3%). Eighteen patients (58%; 95% CI: 40.6-75.4%) achieved an objective response, including four complete responses (12.9%) and 14 partial responses (45.1%). Overall response rate was 51.4% (95% CI: 34.8-67.9%). After a median follow-up of 20 months (range: 2-42), overall survival was 20 months (95% CI: 16-24), and median time to progression was 13 months (95% CI: 7-19). CONCLUSION: This combination shows activity and an acceptable toxicity profile in patients with advanced breast cancer.

Adult↗
PubMed2002

Combined irinotecan, oxaliplatin and 5-fluorouracil in patients with advanced colorectal cancer. a feasibility pilot study.

OBJECTIVES: To evaluate the feasibility and a possible activity range of combination irinotecan (CPT-11), oxaliplatin, and 5-FU in advanced colorectal cancer (ACC). PATIENTS AND METHODS: A total of 53 patients (51% chemoresistant) were treated. Twenty-eight received monthly intravenous oxaliplatin (120 mg/m2) and CPT-11 (250 mg/m2) on day 1 and a course of 5-FU; these constituted the IRI250 group. Twenty-five received monthly intravenous oxaliplatin (120 mg/m2), CPT-11 (300 mg/m2) on day 1, and a course of 5-FU (IRI300 group). 5-FU administration was carried out as follows. Those with predominant hepatic disease (n = 32) received an intra-arterial infusion of 5-FU (2,500 mg/day on days 1-4); these were the IA-FU group. The remaining 21 patients received intravenous 5-FU (2,600 mg/m2 plus leucovorin 500 mg/m2 on days 1 and 15); these constituted the IV-FUFOL group. RESULTS: Intention-to-treat response rate was 54.7% (4 CR, 7.5%). Twelve patients (22.5%) had stable disease; only 4 (7.5%) progressed. Median progression-free and overall survivals were 10 and 18 months, respectively. One-year progression-free and overall survival rates were 44.3 and 67.4%, respectively. Grade 3-4 toxicities included diarrhea (45.3% of patients), neutropenia (52.8%), mucositis (13.2%), and emesis (11.3%). There were 3 treatment-related deaths (5.7%), all in the IA-FU/IRI300 subgroup. Severe adverse effects requiring chemotherapy dose adjustment were observed in 67.9% of the patients, with odds ratios 9.04-fold higher in the IA-FU/IRI300 group (95% CI: 1.07-76.20) and 0.23-fold lower in the IV-FUFOL/IRI250 group (95% CI: 0.05-0.97). CONCLUSION: This combination seems to have substantial activity in ACC. Overall toxicity was unacceptable in the IA-FU and IRI300 groups, with diarrhea and cytopenia constituting the dose-limiting side effects. Tolerance and efficacy profiles achieved with IV oxaliplatin (120 mg/m2 day 1), IV CPT-11 (250 mg/m2 day 1) and IV 5-FU 2.6 g/m2 with IV leucovorin (500 mg/m2 days 1 and 15) was favorable and deserves further investigation.

Adenocarcinoma↗
PubMed2002

Irinotecan, oxaliplatin, and 5-fluorouracil/leucovorin combination chemotherapy in advanced colorectal carcinoma: a phase II study.

The purpose of this study was to evaluate the efficacy and tolerance of a combination of irinotecan, oxaliplatin, and 5-fluorouracil (5-FU)/leucovorin in advanced colorectal cancer (ACC). Twenty-six consecutive patients with ACC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of oxaliplatin (120 mg/m2 intravenously [i.v.] for 2 hours) on day 1, irinotecan (250 mg/m2 i.v. for 90 minutes) on day 1, and 5-FU (2600 mg/m2 plus leucovorin 500 mg/m2 i.v. in a 24-hour infusion) on day 1 and 15, every 4 weeks. Five of the patients (19.2%) had shown previous chemoresistance. One hundred sixty-two cycles were administered (median, 6; range, 3-13 cycles). All patients were evaluated for toxicity; 23 were evaluable for response. According to intention-to-treat, the overall response rate was 69.2% (18 patients; 95% CI: 48.2%-85.7%), including 3 complete remissions (11.5%). Four additional patients (15.3%) had stable disease, and only 1 (3.8%) progressed. Major toxicities were neutropenia and diarrhea. Grade 3 neutropenia occurred in 9 patients (34.6%), and grade 4 occurred in 1 patient (3.8%). Grade 3 diarrhea occurred in 8 patients (30.7%) and grade 4 in 1 patient (3.8%). Other toxicities were mild. After a median follow-up of 15.5 months, the median progression-free survival was 14 months. Seventeen patients (65.4%) are still alive, and the median overall survival has not been reached yet. This combination of irinotecan, oxaliplatin, and 5-FU/leucovorin is fairly well tolerated and shows promising activity in ACC. This treatment merits further comparison with other combination regimens.

Adenocarcinoma↗