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Biomedical subjects

Javier Moreno

Publications and source records attributed to Javier Moreno.

At least 37 records · Page 2Linked to original sources

Tuberculosis in the transplant candidate: importance of early diagnosis and treatment.

BACKGROUND: Transplantation is contraindicated in candidates with active tuberculosis. The present study was undertaken to determine the clinical manifestations of tuberculosis in the transplant candidate and the prognosis of cases that inadvertently undergo transplantation. METHODS: This study was a retrospective study of tuberculosis cases diagnosed among 3,889 transplant candidates. All cases were diagnosed from respiratory or tissue samples obtained in the pretransplant period or during transplantation. RESULTS: We observed 7 cases (0.18%) of active tuberculosis among 3,889 candidates. Two patients had a history of tuberculosis. Tuberculosis was frequently asymptomatic. Three patients had extrapulmonary tuberculosis. Chest radiographs showed residual fibrotic lesions in three patients and noncavitated consolidation in two patients. All of the patients in which the purified protein derivative test was performed were anergic. All patients that inadvertently underwent transplantation were cured. CONCLUSIONS: Aggressive management is required to prevent tuberculosis in transplant candidates. Patients that inadvertently undergo transplantation can be effectively treated when diagnosed early.

Adult↗

Canine leishmaniasis.

Canine leishmaniasis is caused by Leishmania infantum (syn. L. chagasi, in America) and is transmitted by the bite of phlebotomine sand flies. Infected dogs constitute the main domestic reservoir of the parasite and play a key role in transmission to humans, in which the parasite produces visceral leishmaniasis. The increasing awareness that control of the human disease depends on effective control of canine leishmaniasis has promoted, in the last few years, research into leishmanial infection in dogs. Newly available specific reagents and molecular tools have been applied to the detailed investigation of canine leishmaniasis and important advances have been made in elucidating the epidemiology and pathology of the disease. These new findings have led to better understanding of the disease, and have also helped in the development of new diagnostic methods and control measures against the infection, such as insecticide-impregnated collars for dogs, new drugs and treatment protocols, and second generation vaccines, with the hope of not only reducing the heavy burden of the disease among dogs but also reducing the incidence of human visceral leishmaniasis.

Animals↗

Basic assessment of paced activation sequence mapping: implications for practical use.

Some experiences support the use of atrial paced activation sequence mapping, but there is no systematic study assessing its spatial resolution, reproducibility, and influence of pacing parameters. The aim of this study was to evaluate these issues by using a 24-pole catheter positioned at the atrial aspect of the tricuspid and mitral annuli in 15 patients. Bipolar pacing was performed at two sites (right and left atria), 2 cycle lengths (300 and 500 ms) and two outputs (twice and tenfold the late diastolic threshold voltage for 2-ms pulses). The elapsed time between the atrial activation at the two dipoles adjacent to the pacing dipole (activation time [AT]) was measured during each pacing sequence. Changes in cycle length did not modify the AT. The increase in voltage slightly modified the AT (maximum -2 ms at the RA; 95% CI -3 to -1 ms) due to a greater shortening of the conduction time to the dipole located next to the anode. The 95% limits of the intraobserver and interobserver agreements in the AT measurement were -2 to 3 ms and -3 to 3 ms, respectively. The spatial resolution was studied in ten patients by measuring the AT during pacing from each dipole of a 20-pole catheter with a 1-3-1 mm interelectrode distance. The mean AT change was 10 +/- 4 ms per 6 mm of pacing site displacement (95% CI 8-11 ms, range 2.5-20 ms). In conclusion, paced atrial activation sequence analysis is reproducible, accurate, and relatively independent of pacing parameters.

Cardiac Pacing, Artificial↗

Response of TT virus to IFN plus ribavirin treatment in patients with chronic hepatitis C.

AIM: TT virus (TTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations. PEG-IFN plus ribavirin have been useful in the treatment of chronic hepatitis C infection. This study investigated the responses of TT virus (TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy. METHODS: Fifteen patients infected with HCV were treated with PEG-IFN(0.5 microg/body weight/week) and ribavirin (1 000 mg-1 200 mg/daily) for 48 weeks. Blood samples were drawn at the beginning and the end of the therapy. Serum TTV DNA and HCV RNA were quantified by real time PCR. RESULTS: At the beginning of treatment, TTV infection was detected in 10/15 (66.6%) of HCV-infected patients. Loss of serum TTV DNA at the end of therapy occurred in 6/10 (60%) patients. Out of these 6 patients, 4 (67%) became positive for TTV DNA after 6 months of therapy. Regarding HCV viremia, 11/15 (73%) patients were negative for serum HCV RNA after 48 weeks of therapy, 7/11 (64%) of these cases also became negative for TTV DNA following the combined treatment. In the 3/4 (75%) patients who were positive for HCV RNA at the end of therapy, TTV DNA was detected as well. Sustained HCV response at 6 months after treatment was 53% (8/15). CONCLUSION: No TTV sustained response can be achieved in any patient after PEG-IFN plus ribavirin administration.

Adult↗

[Ionic currents and ventricular fibrillation dynamics].

Ventricular fibrillation is the principal immediate cause of sudden cardiac death. Yet, in contrast to other arrhythmias, ventricular fibrillation is considered to be inaccessible to pharmacologic therapy because of its characteristic and apparently never-ending disarray of electrical waves that seem to propagate chaotically throughout the ventricles. Its prevention has historically been focused on the suppression of ventricular ectopy, with the idea of eliminating potential triggers of fibrillation, which from a clinical standpoint has proven to be detrimental. During the last decade, the application of the theory of wave propagation in non-linear excitable media to the study of cardiac fibrillation has led to a dramatic increase in our understanding of its mechanisms. It is now clear that fibrillation is generated and maintained by rotors that gyrate at exceedingly high frequencies. From such rotors emanate spiral waves of excitation that propagate throughout the myocardium in very complex ways. Among the most important factors that determine rotor dynamics are the electrophysiological properties of the ventricular cells, established by their underlying transmembrane ionic currents. Thus, in recent years, studies have focused on the roles played by specific ionic mechanisms and their modulation by antiarrhythmic drugs in ventricular fibrillation dynamics. This review article summarizes the main findings of such studies, which pave the way for a better understanding of fibrillation, and for the development of new pharmacological approaches that aim to prevent rotor formation and maintenance rather than to suppress the triggering ectopic event.

Anti-Arrhythmia Agents↗

[Intravenous enalapril does not prevent tachycardia-induced acute atrial electrical remodeling].

INTRODUCTION AND OBJECTIVES: Recent clinical studies suggest a potential antiarrhythmic role of angiotensin-converting enzyme inhibitors in preventing atrial fibrillation. Studies in an animal model suggested that these drugs may prevent sustained atrial fibrillation by avoiding the occurrence of detrimental atrial electrical remodeling secondary to temporary episodes of fibrillation or atrial tachycardia. We sought to determine whether intravenous enalaprilat, administered at doses habitually used in clinical practice, prevented pacing-induced acute atrial remodeling. PATIENTS AND METHOD: We analyzed 16 patients with no structural heart disease referred for electrophysiologic study due to supraventricular tachycardia. During the control period, right and left atrial effective refractory periods (ERP) were determined before and after a 10-minute period of rapid atrial pacing (250 ms) to quantitatively assess pacing-induced shortening of the ERP. After full recovery, a bolus dose of enalaprilat (0.015 mg/kg) was infused and the measurement and stimulation procedure repeated to quantify remodeling after enalaprilat administration. RESULTS: In the control period, rapid pacing induced a significant 14% reduction (P<.01) in right atrial ERP and an 8% decrease (P<.01) in left atrial ERP as compared to baseline values. In the enalaprilat period, rapid pacing significantly reduced ERP by 15% in the right chamber (P<.01) and 7% in the left chamber (P<.01). There was no significant difference in the extent or time course of ERP shortening between the control and enalaprilat periods. The number of unintentionally induced atrial fibrillation episodes did not differ significantly between the two periods. CONCLUSIONS: Intravenous enalapril does not avoid the occurrence of pacing-induced acute electrical atrial remodeling, modify its time course, or impede the induction of atrial fibrillation.

Adult↗

[Learning process for transseptal puncture guided by intracardiac echocardiography].

We prospectively analyzed the learning process for transseptal catheterization guided by intracardiac echocardiography, in 50 patients who underwent radiofrequency ablation for left atrial arrhythmias. In 20 patients the intracardiac echocardiography catheter was positioned in the right atrium to visualize the fossa ovalis and the tenting of the fossa caused by the Brockenbrough needle. In the other 30 patients, the intracardiac echocardiography catheter was positioned so that it impinged upon the fossa ovalis, and the needle was advanced alongside the intracardiac echocardiography catheter under fluoroscopic guidance in two orthogonal projections. In all but one patient, transseptal catheterization was performed successfully on the first attempt. The learning process for transseptal puncture guided by intracardiac echocardiography was uncomplicated, resulting in a procedure that is safe and effective. The intervention is simplified by positioning the echocardiography catheter at the fossa ovalis and using this as a reference point for fluoroscopic monitoring of the progress of the Brockenbrough needle.

Cardiac Catheterization↗

[Risk stratification and prevention of sudden death in patients with heart failure].

Patients with heart failure can die of progressive refractory heart failure or sudden cardiac death. This article reviews the major clinical predictors of sudden death in patients with heart failure due to left ventricular systolic dysfunction. Although earlier studies have identified many independent univariate predictors of reduced survival in these patients, the positive predictive value of most of them is low. Cardioverter defibrillator implantation has been shown to be the most effective therapy in patients resuscitated after cardiac arrest caused by ventricular fibrillation or poorly tolerated ventricular tachycardia. Low left ventricular ejection fraction, low New York Heart Association functional class, unsustained ventricular tachycardia and inducibility of ventricular arrhythmia in electrophysiological studies may also identify high-risk patients who are candidates for cardioverter defibrillator implantation. The role of amiodarone in preventing sudden death in high-risk patients with heart failure seems to be small. Further studies are needed to improve risk stratification criteria to select patients with heart failure who are candidates for cardioverter defibrillator implantation.

Clinical Trials as Topic↗

Partial splenic embolization for the treatment of hypersplenism in cirrhotic HIV/HCV patients prior to pegylated interferon and ribavirin.

Partial splenic embolization (PSE), a non-surgical treatment for hypersplenism, has also been reported to improve hepatic function. As severe thrombocytopaenia or leukopaenia contraindicate the use of combined therapy with pegylated interferons (PEG-IFNs) and ribavirin (RBV) in HCV-related cirrhosis, we evaluated, from July 2002 to October 2003, the safety and effectiveness of PSE as a procedure to allow therapy for HCV in three Child-Pugh class B cirrhotic patients with hypersplenism and HIV co-infection. HCV genotypes were 1b (n=2) and 3a (n=1). Severe thrombocytopaenia (in all) and leukopaenia (in two) precluded therapy for HCV. PSE was successfully performed in all with a mean infarcted area of 80%, leading to a significant increase in platelet and leukocyte counts that allowed therapy with weight-adjusted RBV and PEG-IFN-alpha-2b (patients 1 and 3) or 180 microg of PEG-IFN-alpha-2a (patient 2) 8 weeks after the procedure. Moderate pain, well controlled with conservative measures, followed PSE in 100% of cases, but during follow-up (mean 422 days) there were no infectious complications or liver decompensation episodes. Although preliminary, these results suggest the potential role of PSE in HIV/HCV-cirrhotic subjects with hypersplenism as a procedure to allow the use of combined PEG-IFN and RBV.

Adult↗

A gibberellin-induced nuclease is localized in the nucleus of wheat aleurone cells undergoing programmed cell death.

The aleurone layer of cereal grains undergoes a gibberellin-regulated process of programmed cell death (PCD) following germination. We have applied a combination of ultrastructural and biochemical approaches to analyze aleurone PCD in intact wheat grains. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay revealed that PCD was initiated in aleurone cells proximal to the embryo and then extended to distal cells. DNA fragmentation and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis revealed PCD of aleurone cells in maize grains, although the process was delayed as compared with wheat. Aleurone cells undergoing PCD showed a rapid vacuolation with high lytic activity in the cytoplasm, whereas the nucleus, which adopted an irregular shape, appeared essentially intact and showed symptoms of degradation at the end of the process. A nuclease activity was identified localized in the nucleus of aleurone cells undergoing PCD, just prior to the appearance of DNA laddering. This nuclease was induced by gibberellic acid treatment and was not detected when gibberellin synthesis was inhibited or in gibberellic acid-insensitive mutants. This nuclease was activated by Ca(2+) and Mg(2+), strongly inhibited by Zn(2+), and showed optimum activity at neutral pH, resembling nucleases involved in apoptosis of animal cells.

Apoptosis↗

Intra-atrial pressure increases rate and organization of waves emanating from the superior pulmonary veins during atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) commonly associates with atrial dilatation by poorly understood mechanisms. We hypothesized that elevation of intra-atrial pressure elicits high-frequency and spatio-temporally organized left atrial (LA) sources emanating from the superior pulmonary veins. METHODS AND RESULTS: We used a stretch-related AF model in the sheep heart to induce stable episodes of AF (>40 minutes) in 9 animals. Video movies of the LA free wall (LAFW) and LA superior pulmonary vein junction (JPV) were obtained by using di-4-ANEPPS. Electrograms from the right atrium were recorded. At intra-atrial pressures >10 cm H2O, the maximum dominant frequency (DFMax) was significantly higher in the JPV than in the LAFW (12.0+/-0.2 and 10.5+/-0.2 Hz, respectively [mean+/-SEM]; P<0.001). Below 10 cm H2O, DFMax was similar in the JPV and LAFW (10.8+/-0.3 versus 10.2+/-0.3 Hz; P=0.6); DFMax in both JPV and LAFW was significantly higher than in the right atrium (7.8+/-0.3 Hz; P<0.001). Analysis of excitation direction in JPV showed positive correlation between intra-atrial pressure and the number of waves emanating from the left superior pulmonary vein (r=0.79, P=0.02) but not from the LAFW (r=0.54, P=0.09). The number of spatio-temporally periodic waves in the JPV correlated with pressure (r=0.92, P=0.002). In 3 cases, JPV rotors were identified with a cycle length equal to 1/DFMax. CONCLUSIONS: We demonstrate for the first time that an increase in intra-atrial pressure increases the rate and organization of waves emanating from the superior pulmonary veins underlying stretch-related AF.

Animals↗

Left atrial flutter after radiofrequency catheter ablation of focal atrial fibrillation.

We report an arrhythmic complication in two patients in whom a procedure directed at isolating one or two pulmonary veins had been performed. The complication was related to pulmonary vein disconnection scars after ablation. Both patients developed new clinical tachycardia (atypical atrial flutter) secondary to a reentrant phenomena in the vicinity of a previously ablated pulmonary vein.

Adult↗

A purL mutant of Sinorhizobium fredii HH103 is symbiotically defective and altered in its lipopolysaccharide.

The pleiotropic phenotype of an auxotrophic purL mutant (SVQ295) of Sinorhizobium fredii HH103 has been investigated. SVQ295 forms colonies that are translucent, produce more slime and absorb less Congo red than those of wild-type strain HH103. SVQ295 did not grow in minimal medium unless the culture was supplemented with thiamin and adenine or with thiamin and AICA-riboside (5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside), an intermediate of purine biosynthesis. Bacterial cultures supplemented with AICA-riboside or adenine reached the same culture density, although the doubling time of SVQ295 cultures containing AICA-riboside was clearly longer. S. fredii SVQ295 induced pseudonodules on Glycine max and failed to nodulate six different legumes. On Glycyrrhiza uralensis, however, nodules showing nitrogenase activity and containing infected plant cells were formed. SVQ295 showed auto-agglutination when grown in liquid TY medium and its lipopolysaccharide (LPS) electrophoretic profile differed from that of its parental strain HH103-1. In addition, four monoclonal antibodies that recognize the LPS of S. fredii HH103 failed to recognize the LPS produced by SVQ295. In contrast, (1)H-NMR spectra of K-antigen capsular polysaccharides (KPS) produced by SVQ295 and the wild-type strain HH103 were similar. Co-inoculation of soybean plants with SVQ295 and SVQ116 (a nodA mutant derivative of HH103) produced nitrogen-fixing nodules that were only occupied by SVQ116.

Animals↗

Evaluation of a specific immunochemotherapy for the treatment of canine visceral leishmaniasis.

The efficacy of specific immunochemotherapy against Leishmania infantum infection in dog was studied. The effects on transmission of the disease, as well as the cellular and humoral immune response were examined. The treated animals showed a significant reduction in the infection rates that were detected in Phlebotomus perniciosus females fed on the dog. The humoral immune response, assayed with an indirect immunofluorescence antibody test (IFAT), did not show significant variations under the influence of the therapy. The characterisation of the peripheral blood mononuclear cells (PBMC) using flow cytometry indicated a significant increase in the proportion of T lymphocytes, especially of CD4/TcR(alpha)(beta)(+) and CD4/CD45RA(+) cells, without showing evidence for modifications in the other leukocyte subsets. Cellular lymphoproliferation studies indicated a lack of a specific response to soluble leishmanial antigen (SLA), but the non-specific lymphoproliferative capacity assayed with phytohemagglutinin (PHA) was maintained.

Animals↗

A novel methodology to develop a foot and mouth disease virus (FMDV) peptide-based vaccine in transgenic plants.

The expression of antigens in transgenic plants has been increasingly used as an alternative to the classical methodologies for antigen expression in the development of experimental vaccines. However, an important limitation in most cases is the low concentration of the recombinant antigens in the plant tissues, which reduces the possibilities of practical applications. Because the site of insertion of the transferred DNA into the cellular chromosomal DNA is at random, different levels of foreign protein expression in independent transformants is expected. Strategies to allow the evaluation of a high number of the transgenic individuals, usually an expensive and very time consuming process, would permit the selection of those plants presenting the highest levels of recombinant protein expression. Here, we present the development of an experimental immunogen based in the expression of a highly immunogenic epitope from foot and mouth disease virus (FMDV) fused to the glucuronidase (gus A) reporter gene, which allows selection of the transgenic plants by the ss-glucuronidase (ssGUS) enzymatic activity. We produced transgenic plants of alfalfa expressing the immunogenic site between amino acid residues 135-160 of structural protein VP1 (VP135-160), fused to the ssGUS protein. Plants expressing the highest levels of the immunogenic epitope VP135-160, analyzed by Western blot, were efficiently selected based on their levels of ssGUS enzymatic activity. The FMDV epitope expressed in plants was highly immunogenic in mice which developed, after immunization, a strong anti-FMDV antibody response against a synthetic peptide representing the region VP135-160, to native virus VP1, and to purified FMDV particles. Additionally, these mice were completely protected against experimental challenge with the virulent virus. To our knowledge, this constitutes the first report of a peptide-based vaccine produced in transgenic plants that induces a protective immune response when used in experimental hosts. Also, these results demonstrated the possibility of using a novel and simple methodology for obtaining transgenic plants expressing high levels of foreign immunogenic epitopes, which could be directly applied in the development of plant-based vaccines.

Animals↗

Canine leishmaniasis: epidemiological risk and the experimental model.

Increasing risk factors are making zoonotic visceral leishmaniasis a growing public health concern in many countries. Domestic dogs constitute the main reservoir of Leishmania infantum and Leishmania chagasi, and play a key role in the transmission to humans. New reagents and tools allow the detailed investigation of canine leishmaniasis, permitting the monitoring of the immunological status of dogs in both natural and experimental infections. Such studies are essential to determine the basis of the canine protective immune response and to establish a laboratory model, a significant aspect for the development of vaccines against canine leishmaniasis.

Animals↗