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Biomedical subjects

A Torres

Publications and source records attributed to A Torres.

At least 73 records · Page 4Linked to original sources

Primary hyperoxaluria type 1 in the Canary Islands: a conformational disease due to I244T mutation in the P11L-containing alanine:glyoxylate aminotransferase.

Primary hyperoxaluria type 1 (PH1) is an inborn error of metabolism resulting from a deficiency of alanine:glyoxylate aminotransferase (AGXT; EC 2.6.1.44). Most of the PH1 alleles detected in the Canary Islands carry the Ile-244 --> Thr (I244T) mutation in the AGXT gene, with 14 of 16 patients homozygous for this mutation. Four polymorphisms within AGXT and regional microsatellites also were shared in their haplotypes (AGXT*LTM), consistent with a founder effect. The consequences of these amino acid changes were investigated. Although I244T alone did not affect AGXT activity or subcellular localization, when present in the same protein molecule as Leu-11 --> Pro (L11P), it resulted in loss of enzymatic activity in soluble cell extracts. Like its normal counterpart, the AGXT*LTM protein was present in the peroxisomes but it was insoluble in detergent-free buffers. The polymorphism L11P behaved as an intragenic modifier of the I244T mutation, with the resulting protein undergoing stable interaction with molecular chaperones and aggregation. This aggregation was temperature-sensitive. AGXT*LTM expressed in Escherichia coli, as a GST-fusion protein, and in insect cells could be purified and retained enzymatic activity. Among various chemical chaperones tested in cell culture, betaine substantially improved the solubility of the mutant protein and the enzymatic activity in cell lysates. In summary, I244T, the second most common mutation responsible for PH1, is a protein conformational disease that may benefit from new therapies with pharmacological chaperones or small molecules to minimize protein aggregation.

Animals↗

Is azithromycin the first-choice macrolide for treatment of community-acquired pneumonia?

Combination treatment with a beta-lactam plus a macrolide may improve the outcome for elderly patients with community-acquired pneumonia (CAP). The prognoses and mortality rates for elderly patients with CAP who receive ceftriaxone combined with a 3-day course of azithromycin or a 10-day course of clarithromycin were compared in an open-label, prospective study. Of 896 assessable patients, 220 received clarithromycin and 383 received azithromycin. There were no significant differences between groups with regard to the severity score defined by the Pneumonia Patient Outcomes Research Team (PORT) study group; the incidence of bacteremia was also not significantly different. However, for patients treated with azithromycin, the length of hospital stay was shorter (mean+/-SD, 7.4+/-5 vs. 9.4+/-7 days; P<.01) and the mortality rate was lower (3.6% vs. 7.2%; P<.05), compared with those treated with clarithromycin. There might be a difference in the outcome for patients with CAP depending on the macrolide used. A shorter treatment course with azithromycin may result in better compliance with therapy.

Adult↗

Cardiovascular risk profile in nondiabetic renal transplant patients: cyclosporine versus tacrolimus.

Calcineurin inhibitors (CIs) contribute to cardiovascular risk (CR) in renal transplant (RT) patients. However, the CR profile in RT patients without preexistent diabetes is not well known. We compared CR factors in 191 nondiabetic RT recipients with functioning grafts beyond 1 year, receivingly either CsA (Neoral; n=100) or tacrolimus (Tac; n= 91). Clinical data and pretransplant CR profiles were similar in both groups. There were no differences in acute rejection episodes and graft survival rates during follow-up. The overall proportions of posttransplant diabetes (9% versus 6%), and of hypertension (73% vs 63%) were similar in both groups. Hyperlipidemia was more frequent in the CsA group (58% vs 31%; P=.0001). The cholesterol levels in the CsA group showed at 3 months (232+/-47 vs 202+/-42 m/dL; P=.0001), 6 months (232+/-49 vs 205+/-41 mg/dL; P=.0001), and 12 months (217+/-50 vs 202+/-40 mg/dL; P=.028), despite receiving a greater proportion of lipid-lowering drugs (49% vs 15%; P=.0001). Logistic regression analysis showed that CsA was an independent predictor of posttransplant hyperlipidemia (OR: 5.8, CI 95%; 3.3-10.7; P=.0001) as were age, female gender, pretransplant dyslipidemia, and body mass index (BMI). Interestingly, an interaction was observed between pretransplant BMI and CIs: Among pretransplant normal weight patients (BMI <25 kg/m2), CsA produced a greater incidence of hyperlipidemia than tacrolimus (58% vs 23%; P=.0001) while not among patients who were overweight (BMI >25 kg/m2: pretransplant 58% vs 42%; P=.341). In conclusion, CsA confers a higher risk of hyperlipidemia after RT in nondiabetic patients, particularly those with normal pretransplant weight.

Adult↗

Obesity favors surgical and infectious complications after renal transplantation.

UNLABELLED: The prevalence of obesity is increasing in the renal transplant population. There are controversial data with respect to posttransplant outcome. We performed a study comparing the incidence of surgical and infectious complications among 40 obese patients (body mass index [BMI] pretransplant > or =30 kg/m2) versus a matched nonobese control group (BMI <30 kg/m2) transplanted at our center between June 1989 and March 2001. RESULTS: There were no differences in patient demographic variables (mean age, gender, cause of renal failure, or percentage of diabetes or hepatitis C virus infection). Donor age, HLA mismatching, sensitization, cold ischemia time, and immunosuppressive regimen were similar in both groups. The mean pretransplant BMI in obese and nonobese patients was 34.1+/-4.0 versus 23.00+/-2.73 kg/m2 (P<.01). The obese group showed a higher incidence of delayed graft function (30% versus 5%, P<.05) and wound infections (12.5%) posttransplant with similar incidences of wound dehiscence, perigraft collections, and graft function at the end of follow up.

Body Mass Index↗

BALB/C mice injected with LSTRA leukemic cell line are cured by in vivo treatment with IL-2 + GM-CSF.

We studied the effects of the in vivo administration of interleukin-2 (IL-2) (at low doses) + GM-CSF in BALB/C mice injected intraperitoneally with LSTRA murine leukemic cell line in order to test the possible role of this immunotherapeutic approach in the eradication of leukemia. Mice were injected intraperitoneally on day -1 with different concentrations of LSTRA cells. On day 0, mice received a lethal dose of TBI of 700 cGy from a Cs(137) source, followed by a single high dose of recombinant human-granulocyte-colony stimulating factor (rh-G-CSF) (1 microg/g) intraperitoneally 2h after TBI. This procedure rescued 80% of mice but only mice injected with the lower concentration of LSTRA cells (10(3)) could be cured. The lethal dose (LD 100/60) of LSTRA in normal mice was 10(4). The subcutaneous administration of rh-IL-2 (4.000 IU/mouse per day, from day +1 to +28) + rm-GM-CSF (1 microg/kg per day) from day +7 to +28 cured mice injected with 10(4) LSTRA cells and 40% of mice injected with 10(5) cells. Mice injected with 10(6) cells died from leukemia. We observed an increase in LAK activity on days +21 and +28 without an increase in NK activity. We show that BALB/C mice injected with LSTRA cell line can be cured by in vivo activation with IL-2 + GM-CSF depending on the cell dose injected. The curability of leukemia was confirmed at the molecular level with a PCR method.

Animals↗

[Second consensus report on the use of antimicrobial agents in exacerbations of chronic obstructive pulmonary disease].

Aware of the importance of chronic obstructive pulmonary disease (COPD), a panel of experts belonging to the Spanish Society of Respiratory Medicine and Thoracic Surgery (SEPAR), the Spanish Society of Chemotherapy (SEQ) and the Spanish Society of Family and Community Medicine (SEMFyC) issued a statement of consensus in 2000 to serve as the basis for adequate antibiotic control of the disease. Three years later, in accordance with significant scientific progress made in this area, the statement has been thoroughly revised. The new paper in fact constitutes a second consensus statement on the use of antibiotics in COPD exacerbations. When several scientific associations expressed interest in joining the project and contributing to it the Spanish Society of Emergency Medicine (SEMES), the Spanish Society of General Medicine (SEMG) and the Spanish Society of Rural and General Medicine (SEMERGEN) their incorporation led SEPAR and SEMFyC to change the structure of the statement and certain aspects of its content. Additionally, a new group of antibiotics, the ketolides, has joined the therapeutic arsenal. Telithromycin, the single representative of the group for the moment, can be considered not only an alternative treatment but even the drug of choice in certain clinical settings that are analyzed in the new statement. Those developments, along with others, such as the increasingly recognized action of levofloxacin against Pseudomonas aeruginosa and the steady action of amoxicillin with clavulanic acid when administered at recommended doses every 8 hours, provide new antimicrobial therapeutic protocols for COPD. Finally, the statement includes a scientific analysis of other groups of antimicrobial agents (macrolides, oral cephalosporins, etc.) and guidelines for both primary care physicians and specialists to follow when prescribing them.

Anti-Bacterial Agents↗

Bacterial infection in exacerbated COPD with changes in sputum characteristics.

We examined the risk factors for bacterial exacerbation, defined as the presence of pathogenic bacteria in sputum, in 90 chronic obstructive pulmonary disease (COPD) patients with an exacerbation and changes in sputum characteristics. Smoking, alcohol, lung function, body mass index, medical visits and treatments were the independent variables assessed using multivariable logistic regression modelling (OR, 95% CI). A bacterial exacerbation was diagnosed in 39 (43.3%) of 90 patients. Bacterial exacerbations were more prevalent among current smokers (OR 3.77, 95% CI 1.17-12.12), in patients with poor compliance with inhalation therapy (OR 3.25, 95% CI 1.18-8.93) and with severe lung function impairment (FEV1 OR 0.96, 95% CI 0.93-1.00). Prior use of antibiotics was a risk factor for Pseudomonas aeruginosa infection (OR 6.06, 95% CI 1.29-28.44) and influenza vaccination appeared to have a protective effect against this infection (OR 0.15, 95% CI 0.03-0.67). We conclude that severe impairment of lung function, smoking and poor compliance with therapy are risk factors for bacterial infection in COPD, and P. aeruginosa should be suspected in patients who have been treated with antibiotics and in those not vaccinated against influenza.

Aged↗

Automatic quantification of viability in epithelial cell cultures by texture analysis.

Quantification of live cells in phase contrast microscopy images allows in vivo assessment of the viability of cultured cells. An automatic screening procedure seems advisable because of the large number of cells that must be counted to achieve reasonable accuracy. This paper presents a method that quantifies necrosis in cell cultures by texture analysis of microscope images. The image is divided into regions of equal size that are classified by means of a segmentation algorithm based on texture analysis into three categories: live cells, necrotic cells and background. The classification uses three discriminant functions, built from parameters derived from the histogram and the co-occurrence matrix and calculated by performing an initial stepwise discriminant analysis on 21 sample images from a training set. The areas occupied by live and necrotic cells and number of live cells have been obtained for primary cellular cultures in intervals of 48 h during 2 weeks. The results have been compared with those obtained by an experienced observer, showing a very good correlation (Pearson's coefficient 0.95, kappa 0.87, N= 1600). A method has been developed that provides an accuracy similar to that provided by an expert, while allowing a much higher number of fields to be counted.

Cell Culture Techniques↗

Characterization of surface n-alkanes and fatty acids of the epiphytic lichen Xanthoria parietina, its photobiont a green alga Trebouxia sp., and its mycobiont, from the Jerusalem hills.

Surface alkanes and fatty acids from the thalli of the lichen Xanthoria parietina, its photobiont Trebouxia sp., and its mycobiont were analysed by GC-MS. The green alga Trebouxia sp. synthesized mainly unsaturated fatty acids such as (Z,Z,Z)-9,12,15-18 : 3 (Z,Z)-9,12-18 : 2 and (Z)-9-18 : 1, and light alkanes C8-C15 (up to 83% of total n-alkanes). However, the mycobiont contained mainly saturated fatty acids such as hexadecanoic (16 : 0) and octadecanoic acid (18 : 0), and also very long-chain n-alkanes C22-C34. Dehydroabietic acid was found in both lichen and mycobiont. The occurrence of different amounts of n-alkanes and fatty acids in the photobionts and mycobionts of X. parietina was shown for the first time. Lichens collected from different locations in the Jerusalem hills contained n-alkanes ranging in concentration from 187 to 211 mg x (g dry wt)-1; n-alkane concentrations in the photobiont and mycobiont were 17-24 and 215-262 mg x (g dry wt)-1, respectively.

Alkanes↗

Bullous scleroderma-like changes in chronic graft-versus-host disease.

Cutaneous graft-versus-host disease (GVHD) is the most common clinical setting for GVHD after bone marrow transplantation. Chronic cutaneous GVHD is categorized according to the type of skin lesions into lichenoid and sclerodermoid variants, but bullous scleroderma-like changes are exceptional. Recently, we studied a patient with these alterations. This is the second case described in the literature.

Adolescent↗

Effectiveness of oral moxifloxacin in standard first-line therapy in community-acquired pneumonia.

Based on recent guidelines for the management of community-acquired pneumonia, this study was designed to evaluate the effectiveness of a new fluoroquinolone compared with standard antimicrobial regimens, in conditions relating as closely as possible to the real world setting. In this study, 564 patients were randomised to either oral moxifloxacin (400 mg o.d.) or to standard oral therapy (amoxicillin 1 g t.i.d. or clarithromycin 500 mg b.i.d. alone or in combination) for up to 14 days using a double-blind procedure. The choice between the three standard regimens was made by the clinician prior to randomisation. Clinical response, quality of life, symptoms, healthcare resources and safety were assessed. In the per-protocol population, clinical success was reported for 201 of 215 (93.5%) and 217 of 231 (93.9%) in the moxifloxacin and standard groups, respectively, at 7-10 days post-therapy. At 28-35 days follow-up, continued clinical cure was observed in 183 of 192 (95.3%) moxifloxacin and 207 of 221 (93.7%) standard groups. Drug-related adverse events were reported in 55 of 274 (20%) moxifloxacin and 86 of 279 (31%) standard patients with diarrhoea >5%. Oral moxifloxacin monotherapy was as effective as, and better tolerated than, optimal antibiotic strategy represented either by mono- or combination therapy (amoxicillin and/or clarithromycin) in community-acquired pneumonia management.

Administration, Oral↗

Hospital-acquired pneumonia: coverage and treatment adequacy of current guidelines.

The American Thoracic Society (ATS) guideline for hospital-acquired pneumonia (HAP) released in 1996 and the Trouillet classification published in 1998 supply different rational foundations for the classification of patients with HAP and for the selection of initial antibiotic therapy. The aims of this study were to assess the level of bacterial coverage and to assess and validate the adequacy of antibiotic strategy of each of these classifications. Intensive care unit-admitted patients (n=71) with suspicion of HAP were evaluated. The ATS and Trouillet classifications demonstrated an accuracy to predict the causative microorganism of 91% and 83% respectively. The ATS and Trouillet antibiotic treatment recommendations were adequate in 79% and 80% of the patients, respectively. The microorganisms implicated in the treatment inadequacy of the ATS guideline were Pseudomonas aeruginosa (n=3), Acinetobacter baumanii (n=1), Stenotrophomonas maltophilia (n=1) and methicillin-resistant Staphylococcus aureus (n=1). P. aeruginosa was implicated with Trouillet treatment inadequacy. The current recommendations for empirical antibiotic treatment of hospital-acquired pneumonia (American Thoracic Society and Trouillet) showed a good ability to predict the involved pathogen. However, considering the resistance pattern of the isolated pathogens, both classifications demonstrated a rather lower treatment adequacy; the main reason was the failure to treat highly resistant strains.

Aged↗