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Biomedical subjects

L Garcia

Publications and source records attributed to L Garcia.

At least 19 recordsLinked to original sources
PubMed2012

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options. We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals. Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein. To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route. Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps. Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology. Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30&#xb1;10 non-overlapping injections per animal. Vector DNA was detectable in all samples tested and ranged from <1 to >3000 vector genome copies per cell. RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium. Left ventricular function remained unchanged over a 3-month follow-up. These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM. This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.

Animals↗
PubMed2006

Noninvasive monitoring of therapeutic gene transfer in animal models of muscular dystrophies.

Muscular dystrophies are a genetically and phenotypically heterogeneous group of degenerative muscle diseases. A subset of them are due to genetic deficiencies in proteins which form the dystrophin-associated complex at the membrane of the myofibers. In this report, we utilized recombinant adeno-associated virus containing a U7 cassette carrying an antisense sequence aimed at inducing exon skipping of the dystrophin gene or containing the alpha-sarcoglycan gene to alleviate the dystrophic phenotype of the mdx and Sgca-null mice, respectively. As these diseases are characterized by cycle of degeneration/regeneration, we postulated that a reporter gene coadministered at the time of the treatment would make it possible to follow the extent of muscle repair. We observed that the murine secreted alkaline phosphatase (muSeAP) level was very much lower in these animal models than in normal mice. Upon treatment of the dystrophic muscle by gene transfer, the level of muSeAP was restored and correlated with the expression of the therapeutic transgene and with the level of muscle improvement. The system described here provides a simple and noninvasive procedure for monitoring the outcome of a therapeutic strategy involving cell survival.

Alkaline Phosphatase↗
PubMed2006

Basal cell carcinoma of the nasolabial fold: an apparently 'benign' tumour that often needs complex surgery.

BACKGROUND: Location of the tumour is a well-known prognostic factor for recurrence of basal cell carcinoma (BCC). We have observed that tumours located in the nasolabial fold may deserve a particular attention. OBJECTIVE: The aim of this study is to evaluate the behaviour of BCC located on the nasolabial fold in comparison to a control group of patients with BCC in lower risk sites, and to detect characteristics which may imply a more complicated treatment or the consideration of adjuvant treatment. METHODS: A series of 24 patients with BCC located on the nasolabial fold were retrospectively recruited from our database of Mohs surgery from January 1997 to December 2000. A control group of 37 patients with BCC located on the cheek or forehead were selected from the same database. The differences between both groups in clinical, surgical and histological terms were evaluated. RESULTS: BCC on the nasolabial fold presented with shorter evolution time from first symptom, had a smaller size, had been less frequently treated before and showed mostly non-aggressive histologic subtype, but needed more surgical stages and more complex reconstruction. CONCLUSION: We have observed that BCC on the nasolabial fold, despite presenting with better clinical and histological features, needed more complicated surgery. In our opinion, this location warrants a particular attention and further prospective studies should be made to corroborate our findings.

Aged↗
PubMed2006

Effectiveness and safety of an emergency department short-stay unit as an alternative to standard inpatient hospitalisation.

BACKGROUND: Emergency department short-stay units (EDSSUs) are currently emerging worldwide as an alternative to standard inpatient hospitalisation. In our hospital, a 960-bed teaching tertiary institution in Barcelona, Spain, an EDSSU has been in operation during winter periods (November-March) since 1997. AIM: To determine the efficacy and safety of our EDSSU. METHODS: Retrospective analysis of activity and quality outcomes, assessment of patient satisfaction levels and determination of the diagnostic-related groups that were mainly responsible for admissions to the EDSSU, comparing the clinical characteristics of those patients with the characteristics of patients with similar clinical diagnoses admitted to standard hospitalisation units. RESULTS: 5666 patients were treated in the EDSSU, with a progressive increase in the number of patients admitted per period, ranging from 707 in 1997-8 to 1227 in 2003-4 (73.5% increase). The mean length of stay ranged from 3.1 to 2.8 days, mortality from 2.5% to 5.1%, home discharge rate from 84% to 90%, and hospital readmission rate within the first week after discharge from 3.9% to 6.2%. In all, 98% of patients were satisfied with their stay at the EDSSU. The main diagnostic-related groups were chronic obstructive pulmonary disease (COPD = 50%) and acute heart failure (28%). Patients with COPD admitted at the EDSSU (n = 545) showed significantly (p = 0.05) lower mean length of stay (3.4 v 12 days) and mortality (1.7% v 8.1%), but a higher hospital readmission rate (9.9% v 7%) than those admitted to standard inpatient units (n = 1961). CONCLUSIONS: In our experience, the EDSSU proved to be an effective and safe alternative to standard inpatient hospitalisation.

Aged↗
PubMed2006

Generic sodium stibogluconate is as safe and effective as branded meglumine antimoniate, for the treatment of tegumentary leishmaniasis in Isiboro Secure Park, Bolivia.

Human cutaneous leishmaniasis (CL) and mucous leishmaniasis (ML) are highly endemic in Isiboro Secure Park, which lies in the Bolivian department of Cochabamba--an area where branded meglumine antimoniate (Glucantime) is expensive and poorly distributed. The safety and efficacy of generic sodium stibogluconate (SSG), from Albert David Ltd, was therefore explored, in CL and ML cases from the park, who were treated with 20 mg/kg.day for 20 and 30 days, respectively. A questionnaire recording adverse effects was completed by a physician in each treatment centre. Efficacy of treatment was assessed at the end of treatment and at follow-ups 1 month and 3, 6 and 12 months later. Overall, 146 patients completed treatment with SSG in 2003-2004. No fatalities or severe adverse effects were reported but mild to moderate adverse effects were noted in 41 (28%) of the patients. The incidence of adverse effects was significantly higher among the cases of ML than among the cases of CL. Of the 86 patients with CL who completed 6 months of follow-up, 81 (94.2%) were considered to have been clinically cured; a comparable cohort of 69 CL cases who had been treated with Glucantime in 2001-2002 showed a similar frequency of clinical cure (90%). Generic SSG was shown to be safe and efficacious for the treatment of tegumentary leishmaniasis in Bolivia. Being several times cheaper than Glucantime, it could contribute to improving the access of CL and ML patients to treatment, not only in Bolivia but also in other countries of Latin America.

Adult↗
PubMed2005

Topological instability along invariant surfaces and pseudochaotic transport.

The paper describes the complex topological structure of invariant surfaces that appears in a quasi-stationary regime of the tokamak plasma, and it considers in detail anomalous transport of particles along the invariant surfaces (isosurfaces) that have topological genus greater than 1. Such dynamics is pseudochaotic; i.e. it has a zero Lyapunov exponent. Simulations discover such surfaces in confined plasmas under a fairly low ratio of pressure to the magnetic field energy (beta). The isosurfaces correspond to quasi-coherent structures called "streamers" and the streamers are connected by filaments. We study distribution of time of particle separation, Poincaré; recurrences of trajectories, and first time arrival to the system's edge. A model of a multibar-in-square billiard, introduced by Carreras et al. [Chaos 13, 1175 (2003)] is studied with renormalization group method to obtain a distribution of the first time of particles arrival to the edge as a function of the number of bars, which appears to be power-like. The characteristic exponent of this distribution is discussed with respect to its dependence on the number of filaments that connect adjacent streamers.

Journal Article↗
PubMed2005

Myogenic program induction in mature fat tissue (with MyoD expression).

MyoD exerts a master transcriptional control over the myogenic differentiation cascade. Here, we study different approaches to induce myogenic transdifferentiation in mature adipocytes utilizing MyoD gene transfer. Organotypic cultures of fat tissue and a long-term culture of in vitro differentiated adipocytes deduced that MyoD provoked morphological changes in mature adipocytes that can be summarized as loss of fat content, acquisition of a fusiform shape and eventual fusion with committed neighbor cells. In vivo, MyoD gene transfer into rat interscapular and inguinal fat pads demonstrated that while structural proteins of muscle lineage were expressed, they co-existed with specific adipocyte proteins. Expression of these proteins diminished over time likewise the fat content. The transdifferentiation process initiated by MyoD did not require cell cycle progression and was well tolerated by the fully differentiated and mature adipocytes.

Adenoviridae↗
PubMed2005

Randomized, controlled trial comparing the retention of a flowable restorative system with a conventional resin sealant: one-year follow up.

UNLABELLED: This clinical trial evaluated the retention rate of a flowable restorative system (Bond 1 + Flow-It!) used as a pit-and-fissure sealant compared with a conventional filled resin sealant (Fluroshield) over a 1-year period. METHOD: Using a half-mouth design, 160 sealants (80 in primary and 80 in permanent teeth) were placed on sound first/second primary molars and first permanent molars of 40 children aged between 4 and 7 years. For both primary and permanent dentitions, half the teeth (n = 40) were sealed with Fluroshield and half (n = 40) with Bond 1 + Flow-It! Teeth were evaluated at baseline, 6- and 12-month intervals. RESULTS: For both materials, there was no total loss of sealants placed on either the primary or permanent molars over 1 year. From Fluroshield sealants placed on primary teeth, 33 were completely intact after 6 months and 31 after 1 year. From those placed on permanent molars, no loss of material was observed after 6 months, while partial loss was noticed on 5% of teeth at 1-year recall. For Flow-It! resin applied on primary molars, partial loss of material was observed in only 1 sealant after 6 months and in 2 sealants after 1 year. On permanent teeth, 100% retention rate was observed over a 1-year follow up. There was a statistically significant difference (P < 0.01) between the sealing materials on primary but not permanent teeth, and, overall, Flow-It! sealants presented a higher retention rate at both 6-month and 1-year evaluations. Significant differences (P < 0.01) between baseline and the other evaluation periods were also observed. CONCLUSION: It may be concluded that the flowable restorative system yielded optimal retention on both primary and permanent molars. Its retention rate was significantly higher than that of the conventional pit-and-fissure sealant on primary teeth.

Bisphenol A-Glycidyl Methacrylate↗
PubMed2005

Spatial distribution of Salmonella, Escherichia coli O157:H7, and other bacterial populations in commercial and laboratory-scale sprouting mung bean beds.

The reliability of testing spent irrigation water to assess the microbiological status of sprouting mung bean beds has been investigated. In commercial trials, the distribution of opportunistic contaminants within 32 bean sprout beds (25 kg of mung beans per bin) was assessed 48 h after germination. The prevalence of generic Escherichia coli, thermotolerant coliforms, and Aeromonas in sprouts (n = 288) was 5, 11, and 39%, respectively, and 57, 70, and 79% in the corresponding spent irrigation water samples (n = 96). Contamination was heterogeneously distributed within the seedbed. In laboratory trials, beans inoculated with a five-strain cocktail of either Salmonella or E. coli O157:H7 (10(3) to 10(4) CFU/g) were introduced (1 g/500 g of noninoculated seeds) at defined locations (top, middle, or base), and the beans were then sprouted for 48 h. When seeds inoculated with pathogens were introduced at the base or top of the seedbed, the pathogens were typically restricted to these sites and resulted in 44% of the spent irrigation water samples returning false-negative results. Introducing inoculated beans into the middle or at the presoak stage enhanced the distribution of both pathogens within the subsequent sprout bed and resulted in comparable levels recovered in spent irrigation water. The study demonstrated that even though screening a single sample of spent irrigation water is more reliable than testing sprouts directly, it does not provide an accurate assessment of the microbiological status of sprouting mung bean beds. Such limitations may be addressed by ensuring that bean batches are mixed prior to use and by taking spent irrigation water samples from multiple sites at the latter stages of the sprouting process.

Agriculture↗
PubMed2004

[Metabolic imaging by positron emission tomography using [18F] fluorodeoxiglucose in developmental disorders].

INTRODUCTION: Developmental disorders are a common pathological condition in Neuropaediatrics and do not usually present characteristic anatomical alterations in the different neuroanatomical imaging tests that can be employed, such as computerised axial tomography or magnetic resonance (MR). Positron emission tomography (PET) using [18F] fluorodeoxiglucose (PET FDG), one of the battery of imaging tests currently available, enables us to obtain data about brain activity in a non invasive manner. PATIENTS AND METHODS: A group of 39 patients with developmental disorders from the Hospital del Mar was analysed. They were submitted to PET FDG brain metabolism tests and in some cases hybrid PET MR images were also obtained; findings were then correlated against the clinical progression of the patients. RESULTS AND CONCLUSIONS: The alterations that were observed showed predominantly bilateral thalamic, mesial temporal and orbital frontal hypometabolism. This alteration of the limbic system, which has no correlation with anatomical damage, can be a predictor of the clinical progression and of the confirmation of the presence of alterations in the brain functions in this type of patients.

Brain↗
PubMed2004

New features of rubella in Spain: the evidence of an outbreak.

In most of western Europe the rubella vaccine coverage is high. However, prior to the introduction of the vaccine in Latin America, rubella susceptibility in women of childbearing age was 10-25%. Forty one (93%) countries in Latin America have adopted the rubella vaccine since 2002. The adult immigrant population in Spain constitutes a group of susceptibles. In February 2003, the Madrid Community Measles Elimination Plan detected an increase in rubella notifications in women who had been born in Latin America. A descriptive study was undertaken to characterise the outbreak. A confirmed case was a person with fever or rash and a positive IgM serology, and living in Madrid, between 1 December 2002 and 31 March 2003. The secondary attack rate (SAR) per household was calculated. A total of 19 cases of rubella were identified, 15 were confirmed and 4 were probable cases. Fourteen (73.7%) cases were women at childbearing age. The mean age was 25.1 years. One pregnancy was diagnosed with a voluntary termination. Eleven (57.9%) cases were from Ecuador. The mean time of residence in Spain was 41 months. None of the cases or the 54 (78.3%) household contacts had been vaccinated against rubella. The SAR was 9.1%. This study showed the spread of rubella in the susceptible Latin American Community that is resident in Madrid. The interventions proposed were a vaccination programme towards immigrants, a health education campaign to prevent congenital rubella, and a health professional training programme case management.

Adolescent↗
PubMed2004

Regulation of intracellular chloride concentration in rat lactotrope cells and its relation to the membrane resting potential.

Rat lactotrope cells in primary culture exhibit physiological properties closely associated with chloride ions (Cl-) homeostasis. In this work, we studied the regulation of intracellular Cl- concentrations ([Cl-]i) and its relation to the membrane resting potential, using a combination of electrophysiology and spectrofluorimetry. Variations in [Cl-]i resulting from the patch clamp technique, pHi, antagonists of Cl(-)-Ca(2+)-dependent channels, an anion exchanger antagonist, and an antagonist of K(+)-Cl- cotransport were considered with respect to their involvement in membrane potential. We show that: (i) The patch-pipette does not always impose its Cl- concentration. (ii) In rat lactotrope cells, membrane resting potential is partially determined by [Cl-]i. (iii) Besides ion channel activity, electroneutral ion transports (cotransports such as K(+)-Cl- and Na(+)-K(+)-2Cl-) participate actively in maintaining a high [Cl-]i. (iv) Finally, Cl- homeostasis is probably linked to cell energetics.

Animals↗
PubMed2004

Interactions between intracellular chloride concentrations, intracellular pH and energetic status in rat lactotrope cells in primary culture.

Rat lactotrope cells in primary cultures have a higher intracellular Cl- concentration ([Cl-]i) than that predicted by a passive distribution across the membrane. This suggests that active cellular mechanisms ensure this ionic equilibrium. In this study, we examined the interactions between pHi, [Cl-]i regulation and cell energetics. We analyzed: 1. the interactions between extracellular Cl- concentrations, [Cl-]i and cellular energy; 2. the influence of [Cl-]i on respiratory chain function; 3. the correlation with glycolysis and; 4. the role played by pHi in these cellular mechanisms. We show that low [Cl-]i decreases ATP cell content, ATP/ADP ratio and modify phosphorylative oxidations. ATP production is rather due to the anaerobic pathway of the glucose metabolism than the aerobic one and depends also on other metabolic substrates among which glutamine probably has a special role. Finally, pHi appears as a determinant in the balance between aerobic and anaerobic pathways. These results are discussed in relation to the role of Cl- in normal and pathological (effect of hypoxia on mature and immature neurons) cell situations.

Adenosine Triphosphate↗
PubMed2003

Absence of immunoglobulin E synthesis and airway eosinophilia by vaccination with plasmid DNA encoding ProDer p 1.

BACKGROUND: Various studies have shown that immunization with naked DNA encoding allergens induces T helper 1(Th1)-biased non-allergic responses. OBJECTIVE: To evaluate the polarization of the immune responses induced by vaccinations with plasmid DNA encoding the major mite allergen precursor ProDer p 1. METHODS: A DNA vaccine was constructed on the basis of a synthetic cDNA encoding ProDer p 1 with optimized codon usage. The immunogenicity of ProDer p 1 DNA in CBA/J mice was compared with that of purified natural Der p 1 or recombinant ProDer p 1 adjuvanted with alum. Vaccinated mice were subsequently exposed to aerosolized house dust mite extracts to provoke airway inflammation. The presence of inflammatory cells was examined in bronchoalveolar lavage (BAL) fluids and allergen-specific T cell reactivity was measured. RESULTS: Naive mice immunized with ProDer p 1 DNA developed Th1 immune responses characterized by high titres of specific IgG2a antibodies, low titres of specific IgG1 and, remarkably, the absence of anti-ProDer p 1 IgE. No specific responses were observed in animals vaccinated with the blank DNA vector. By contrast, natural Der p 1 or recombinant ProDer p 1 adsorbed to alum induced pronounced Th2 allergic responses with strong specific IgG1 and IgE titres. Spleen cells from DNA ProDer p 1-vaccinated mice secreted high levels of IFN-gamma and low production of IL-5. Conversely, both adjuvanted allergens stimulated typical Th2-type cytokine profile characterized by high and low levels of IL-5 and IFN-gamma, respectively. Whereas BAL eosinophilia was clearly observed in Der p 1-immunized animals, ProDer p 1 DNA as well as ProDer p 1 vaccinations prevented airway eosinophil infiltrations. CONCLUSIONS: These results suggest that vaccination with DNA encoding ProDer p 1 effectively fails to induce the allergen-induced IgE synthesis and airway cell infiltration. Plasmid DNA encoding ProDer p 1 may provide a novel approach for the treatment of house dust mite allergy.

Animals↗
PubMed2003

Topological instability along filamented invariant surfaces.

In dynamical systems with a zero Lyapunov exponent, weak mixing can be governed by a specific topological structure of some surfaces that are invariant with respect to particle dynamics. In particular, when the genus of the invariant surfaces is more than one, they may have weak mixing and the corresponding fractional kinetics. This possibility is demonstrated by using a typical example from plasma physics, a three-dimensional resistive pressure-gradient-driven turbulence model. In a toroidal geometry and with a low-pressure gradient, this model shows the emergence of quasicoherent structures. In this situation, the isosurfaces of the velocity stream function have a web structure with filamentary surfaces emerging from the outer region of the torus and covering the inner region. The filamentary surfaces can result in stochastic jets of particles that cause a "topological instability." In such a situation, particle transport along the surfaces is of the anomalous superdiffusion type.

Computer Simulation↗
PubMed2002

Effects of antibiotics on protected specimen brush sampling in ventilator-associated pneumonia.

The effects of antibiotic treatment on the results of protected specimen brushing (PSB) in ventilator-associated pneumonia were prospectively assessed by performing this procedure before antibiotic treatment, and 12, 24, 48 and 72 h after initiation of antibiotic treatment, in 35 ventilated patients who developed pneumonia during mechanical ventilation. The number of micro-organisms isolated, their concentration (colony-forming units (cfu) mL(-1)), and the number of cases with a positive PSB (> or =10(3) cfu x mL(-1)) were evaluated. Within 12 h of the initiation of effective antibiotic treatment a rapid, significant decrease in the numbers of organisms isolated, their individual concentrations and the percentage of positive PSB results were observed. Certain bacterial species (Streptococcus pneumoniae, Haemophilus influenzee) appeared to be more vulnerable to antibiotics than others (Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumanni). This data confirms that prior antibiotic treatment, even after only a few hours of activity, significantly decreases the sensitivity of protected brush specimen; this effect appears to be particularly marked among the species involved in early ventilator associated pneumonia.

Adolescent↗