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Biomedical subjects

A Pascual

Publications and source records attributed to A Pascual.

At least 19 recordsLinked to original sources
PubMed2005

Activity of cefepime and carbapenems in experimental pneumonia caused by porin-deficient Klebsiella pneumoniae producing FOX-5 beta-lactamase.

The in-vivo activities of cefepime, imipenem and meropenem against the porin-deficient strain Klebsiella pneumoniae C2 and its derivative K. pneumoniae C2(pMG252) coding for the AmpC-type beta-lactamase FOX-5 were determined. Bactericidal activities were determined with the kill-curve method. A pneumonia model in guinea-pigs was developed, and Cmax, t(1/2) and DeltaT/MIC were calculated for the three agents tested. Animals were treated for 72 h with sterile saline (control group) or with cefepime, imipenem or meropenem (240 mg/kg/day, intramuscularly, three times daily). Bacterial counts in lungs (log10 CFU/g tissue) were determined by serial dilution. MICs (mg/L) of cefepime, imipenem and meropenem against K. pneumoniae C2/K. pneumoniae C2(pMG252), determined by macrodilution, were: 0.5/4, 0.5/0.5 and 0.25/0.5, respectively. Bacterial counts in the lungs of animals infected with K. pneumoniae C2 and treated with antimicrobial agents were always lower than in the control group (cefepime, 4.4 +/- 0.5; imipenem, 4.6 +/- 0.4; meropenem, 4.7 +/- 0.5; control group, 5.6 +/- 0.8; p <0.01). No significant differences were observed among the groups receiving therapy (p >0.05). Bacterial lung clearance was higher in treated animals than in control animals following infection with K. pneumoniae C2(pMG252) (cefepime, 4.5 +/- 0.4; imipenem, 4.0 +/- 0.3; meropenem, 4.6 +/- 0.4; control group, 6.1 +/- 0.6; p <0.01), with imipenem producing better clearance than either cefepime or meropenem (p <0.05). Thus, in the guinea-pig pneumonia model, cefepime, imipenem and meropenem were each effective against the porin-deficient K. pneumoniae strain C2 and its derivative expressing the plasmid-mediated AmpC type beta-lactamase FOX-5.

Animals↗
PubMed2004

Non-invasive interventions for improving well-being and quality of life in patients with lung cancer.

BACKGROUND: Lung cancer is one of the leading causes of death globally. Despite advances in treatment, outlook for the majority of patients remains grim and most face a pessimistic outlook accompanied by sometimes devastating effects on emotional and psychological health. Although chemotherapy is accepted as an effective treatment for advanced lung cancer, the high prevalence of treatment-related side effects as well the symptoms of disease progression highlight the need for high quality palliative and supportive care to minimise symptom distress and to promote quality of life. OBJECTIVES: To assess the effectiveness of non-invasive interventions delivered by healthcare professionals in improving symptoms, psychological functioning and quality of life in patients with lung cancer. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2003), MEDLINE (1966-March 2003), EMBASE (1974-March 2003), CINAHL (1982-September 2002), CancerLit (1975-October 2002), PsycINFO (1873-March 2003), reference lists of relevant articles and contact with authors. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials assessing the effects of non-invasive interventions in improving well-being and quality of life in patients diagnosed with lung cancer. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed relevant studies for inclusion. Data extraction and quality assessment of relevant studies was performed by one reviewer and checked by a second reviewer. MAIN RESULTS: Nine trials were included and categorised into six groups. Two trials of a nursing intervention to manage breathlessness showed benefit on symptom experience, performance status and emotional functioning. Three trials assessed structured nursing programmes and found positive effects on delay in clinical deterioration, dependency and symptom distress, and improvements in emotional functioning and satisfaction with care. One trial assessing counselling showed benefit on some emotional components of the illness but findings were not conclusive. One trial assessing an exercise programme, found a beneficial effect on self-empowerment. One trial of nutritional interventions found positive effects for increasing energy intake, but no improvement in quality of life. One trial of reflexology showed some positive, but short-lasting effects on anxiety. REVIEWERS' CONCLUSIONS: Nurse follow-up programmes and a nurse intervention to manage breathlessness may produce beneficial effects. Psychotherapeutic study indicates that counselling may help patients cope more effectively with emotional symptoms, but the evidence is not conclusive. Findings from the included studies reinforce the necessity for increased training and education of healthcare professionals giving in these interventions. More research, of higher methodological quality is needed in this area to explore possible underlying explanatory mechanisms.

Exercise↗
PubMed2004

Cerebral fluid edema: an unusual complication of ventriculoperitoneal shunts.

INTRODUCTION: A case of accumulation of CSF into the brain parenchyma simulating a brain tumor, secondary to an obstructed ventriculoperitoneal shunt, is presented. Until now, only seven cases of this rare complication have been described. CASE REPORT: Magnetic resonance showed an expansive, low-density intracranial lesion on the right frontal and parietal lobe. This mass was biopsied, but no tumor was found and the diagnosis was brain edema. CONCLUSION: The mistake in the diagnosis was due to the clinical symptoms and to the MR images.

Brain Edema↗
PubMed2004

Antimicrobial susceptibility and mechanisms of resistance to quinolones and beta-lactams in Acinetobacter genospecies 3.

Antimicrobial susceptibility was determined in 15 epidemiologically unrelated clinical isolates of Acinetobacter genospecies 3. Moreover, the mechanisms of resistance to some beta-lactam antibiotics may be associated with the presence of a chromosomal cephalosporinase, AmpC, and the resistance to quinolones related to mutations in the gyrA and parC genes.

Acinetobacter↗
PubMed2003

Detection of the plasmid-mediated quinolone resistance determinant qnr among clinical isolates of Klebsiella pneumoniae producing AmpC-type beta-lactamase.

OBJECTIVES: Plasmid pMG252 contains the qnr locus, which is responsible for low-level resistance to quinolones by protecting the DNA gyrase. pMG252 also encodes the AmpC-type beta-lactamase (pACBL), FOX-5. The aim of this study was to determine the prevalence of qnr in strains from different geographical locations in America and Europe. METHODS: Four hundred and twenty-five (159 Klebsiella pneumoniae and 266 Escherichia coli) clinical isolates were studied. The detection of qnr was by PCR using specific primers for an internal fragment of 543 bp. RESULTS: qnr was detected in three cefoxitin-resistant K. pneumoniae strains, which also produced a pACBL. None of the E. coli isolates tested contained qnr. The three qnr-positive K. pneumoniae came from the USA, and all transferred a conjugative plasmid coding for cefoxitin resistance to E. coli J53. qnr was also transferred by the same plasmid in two out of the three strains. The sequences of amplified qnr fragments from the three strains were identical to the qnr sequence from pMG252. CONCLUSIONS: The qnr determinant is uncommon among clinical isolates of K. pneumoniae and E. coli, but its identification in three pACBL+ K. pneumoniae from the USA indicates the emergence of this quinolone resistance mechanism.

Bacterial Proteins↗
PubMed2003

Accumulation and activity of cethromycin (ABT-773) within human polymorphonuclear leucocytes.

OBJECTIVES: To evaluate the penetration of ketolide cethromycin (ABT-773) into human polymorphonuclear leucocytes (PMNs) and its intracellular activity. METHODS: The uptake of radiolabelled cethromycin by PMNs was determined by a velocity gradient centrifugation technique. The activity of cethromycin against intracellular Staphylococcus aureus ATCC 25923 in PMNs was also evaluated. RESULTS: The cellular to extracellular concentration (C/E) ratio for cethromycin was >200 at an extracellular concentration of 2 mg/L. The uptake of cethromycin into PMNs was rapid and saturable. Cethromycin was slowly released from the loaded PMNs (cell associated drug>50% after 2 h of incubation). Intracellular penetration was significantly affected by the environmental temperature (C/E ratio at 4 degrees C and 37 degrees C: 13 +/- 6 and 226 +/- 31, respectively; P < 0.05), by cell viability (C/E ratio for dead and viable cells: 100 +/- 38 and 226 +/- 31, respectively; P < 0.05), by pH (C/E ratio was significantly increased at basic pH) and by the metabolic inhibitors 2,4-dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone. The intracellular accumulation of cethromycin also decreased significantly when cells were activated with phorbol myristate acetate or opsonized zymosan. These data indicate that a potentially active mechanism could be involved in the uptake of cethromycin by PMNs. At high extracellular concentrations of 5 and 10 mg/L, cethromycin showed significant intracellular activity against S. aureus. CONCLUSIONS: Cethromycin achieves high intracellular concentrations within human PMNs, remaining active intracellularly.

2,4-Dinitrophenol↗
PubMed2003

Evidence of Wallerian degeneration in normal appearing white matter in the early stages of relapsing-remitting multiple sclerosis: a HMRS study.

OBJECTIVE: Wallerian degeneration in normal appearing white matter in early relapsing-remitting multiple sclerosis (RRMS), and its correlation with the number of relapses and disease duration. Background Recent pathological studies have demonstrated Wallerian degeneration in normal appearing white matter (NAWM) in multiple sclerosis (MS), in established RRMS, and in chronic MS. However, the presence of Wallerian degeneration early in the disease and its correlation with relapse and with disease duration has not been studied. METHODS: We performed proton magnetic resonance spectroscopic imaging in 21 MS patients, and 4 healthy controls, age and gender matched, aged under 45 years, with a maximum of 4 years since first bout, and an EDSS score of less than 3.0. N-acetyl-aspartate (NAA) (an index of axonal integrity) was measured in the NAWM from the pons and the cerebellar peduncles. RESULTS: We observed that the NAA levels were abnormally low in the NAWM in the early RRMS patients (p = 0.04, Student's t-test). The decrease in the NAA concentration correlated with disease duration in the two areas studied (p = 0.03 for pons and p = 0.04 for cerebellar peduncle); and with the number of previous relapses (Pearson's correlation = -0.582, p < 0.002). CONCLUSION: Wallerian degeneration measured by the NAA concentration at pons and cerebellar peduncles is present early in the disease and correlates with the number of relapses and disease duration.

Adolescent↗
PubMed2003

Induction of tyrosine kinase receptor b by retinoic acid allows brain-derived neurotrophic factor-induced amyloid precursor protein gene expression in human SH-SY5Y neuroblastoma cells.

Retinoic acid (RA) is a potent regulator of morphogenesis, growth and cell differentiation. Incubation with RA causes arrest of proliferation and neurite extension in SH-SY5Y cells, a neuroblastoma cell line of human origin. In these cells, RA regulates the expression of the beta-amyloid precursor protein. The retinoid increases the levels of intracellular and secreted forms of APP (amyloid precursor protein), APP-mRNA levels and the activity of the APP promoter in transient transfection studies. These responses require long periods of exposition to the ligand, thus suggesting a nondirect effect of the RA receptors on the APP gene. Also in these cells, RA induces the expression of TrkB, the tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF), and 4 days of pretreatment with retinoic acid confers BDNF responsiveness to the APP promoter.

Amyloid beta-Protein Precursor↗
PubMed2003

Evaluation of the WIDER I system for antimicrobial susceptibility testing of clinical isolates of Haemophilus influenzae and Streptococcus pneumoniae.

The aim of this study was to evaluate the WIDER I system for susceptibility testing of Haemophilus influenzae and Streptococcus pneumoniae. MICs of 12 antimicrobials against 42 H. influenzae and 58 S. pneumoniae strains were determined using 1W MIC panels and compared with those obtained by microdilution. Overall essential agreements were >99%. Very major errors were not detected. Major errors occurred with ampicillin (1.7% H. influenzae). Minor errors were 2.3% (amoxicillin-clavulanate, cefuroxime, chloramphenicol), 7.1% (ampicillin) and 16.7% (clarithromycin) for H. influenzae, and 1.7% (chloramphenicol, erythromycin, meropenem), 3.4% (amoxicillin-clavulanate, cefuroxime, tetracycline) and 8.6% (levofloxacin) for S. pneumoniae. The WIDER I system is a reliable method for susceptibility testing of H. influenzae and S. pneumoniae.

Anti-Bacterial Agents↗
PubMed2003

Infections by Neisseria meningitidis serogroup X in Spain.

We describe an atypical presentation of bacteremia caused by N. meningitidis serogroup X. By multilocus sequence typing the isolate was characterized to the sequence type 2139, which is not related with the clonal complex recently isolated in Africa. Since 1984, only six cases of serogroup X N. meningitidis infections have been diagnosed in Spain. Nevertheless, after the application of the conjugated vaccine, attention should be paid to the emergence of infections caused by unusual serogroups of N. meningitidis.

Anti-Bacterial Agents↗
PubMed2003

[In vitro activity of azithromycin against clinical isolates of Acinetobacter baumannii].

The activity of azithromycin against 225 clinical strains of Acinetobacter baumannii isolated consecutively from 26 Spanish hospitals in November 2000 was studied. The MICs of azithromycin were determined by microdilution, according to the NCCLS guidelines. The bactericidal activity of azithromycin against 15 clonally unrelated A. baumannii strains with different antimicrobial susceptibility patterns was tested using the subculture method. The killing-curves method was also performed against five strains with different susceptibility to azithromycin. The MIC(50) and MIC(90) of azithromycin were 32 and 64 mg/l, respectively. Moderate bactericidal activity was observed in 14 out of the 15 strains evaluated by the subculture method (MBCs from 1 to 4 dilution steps higher than the MICs) and by the killing-curve method. For three strains the number of CFU/ml was reduced 1 to 1.4 log by concentrations of azithromycin equivalent to 1 and 4 times their MICs. lt is concluded that azithromycin has moderate bactericidal activity against the strains of A. baumannii evaluated.

Acinetobacter Infections↗
PubMed2002

Pathogenesis of catheter-related infections: lessons for new designs.

In the last decade, two main strategies have been employed in the prevention of catheter-related infections: the creation of anti-adhesive biomaterials using physicochemical methods, and the incorporation of antimicrobial or antiseptic agents into current polymer biomaterials. There has been limited success with the first approach. Intravascular catheters and cuffs with an antimicrobial coating have been developed in recent years. Nevertheless, preventive strategies should avoid the use of therapeutic antibiotics. Exposure to antimicrobial agents could favor the development of resistance or the expression of genes responsible for biofilm formation. The use of these catheters should be restricted to situations where the rate of infection is high despite adherence to other strategies that do not incorporate antimicrobial agents. Better knowledge of the pathogenesis of catheter-related infections will facilitate the design of new devices that avoid the use of antimicrobial agents and decrease the risk of associated bloodstream infections. This could include the use of 'biospecific polymers' coated with anti-adhesive molecules or the use of agents which might block the expression of genes controlling biofilm formation for the most prevalent pathogens.

Bacterial Adhesion↗
PubMed2002

High clinical inflammatory activity prior to the development of secondary progression: a prospective 5-year follow-up study.

OBJECTIVE: To study if there are different patterns of clinical activity--measured by the annual exacerbation rate (AER)--among relapsing-remitting multiple sderosis (RRMS), "early" secondary multiple sclerosis (SPMS) and "late" SPMS. METHODS: A prospective 5-year follow-up study in 80 MS patients has been carried out, calculating the AER and the mean expanded disability status scale (EDSS) change rate (MCR). RESULTS: A significant difference on the AER, among RRMS, early SPMS and late SPMS, has been found. CONCLUSIONS: The SPMS has a high clinical inflammatory activity before and during its transformation from a RRMS.

Adult↗
PubMed2001

Localization of long-term memory within the Drosophila mushroom body.

The mushroom bodies, substructures of the Drosophila brain, are involved in olfactory learning and short-term memory, but their role in long-term memory is unknown. Here we show that the alpha-lobes-absent (ala) mutant lacks either the two vertical lobes of the mushroom body or two of the three median lobes which contain branches of vertical lobe neurons. This unique phenotype allows analysis of mushroom body function. Long-term memory required the presence of the vertical lobes but not the median lobes. Short-term memory was normal in flies without either vertical lobes or the two median lobes studied.

Animals↗
PubMed2001

Glutamine potentiates TNF-alpha-induced tumor cytotoxicity.

L-glutamine (Gln) sensitizes tumor cells to tumor necrosis factor (TNF)-alpha-induced cytotoxicity. The type and mechanism of cell death induced by TNF-alpha was studied in Ehrlich ascites tumor (EAT)-bearing mice fed a Gln-enriched diet (GED; where 30% of the total dietary nitrogen was from Gln). A high rate of Gln oxidation promotes a selective depletion of mitochondrial glutathione (mtGSH) content to approximately 58% of the level found in tumor mitochondria of mice fed a nutritionally complete elemental diet (standard diet, SD). The mechanism of mtGSH depletion involves a glutamate-induced inhibition of GSH transport from the cytosol into mitochondria. The increase in reactive oxygen intermediates (ROIs) production induced by TNF-alpha further depletes mtGSH to approximately 35% of control values, which associates with a decrease in the mitochondrial transmembrane potential (MMP), and elicits mitochondrial membrane permeabilization and release of cytochrome c. Mitochondrial membrane permeabilization was also found in intact tumor cells cultured with a Gln-enriched medium under conditions of buthionine sulfoximine (BSO)-induced selective GSH synthesis inhibition. Enforced expression of the bcl-2 gene in tumor cells could not avoid the glutamine- and TNF-alpha-induced cell death under conditions of mtGSH depletion. However, addition of GSH ester, which delivers free intracellular GSH and increases mtGSH levels, preserved cell viability. These findings show that glutamine oxidation and TNF-alpha, by causing a change in the glutathione redox status within tumor mitochondria, activates the molecular mechanism of apoptotic cell death.

Adenosine Triphosphate↗
PubMed2001

Synthesis and structure-activity relationships of benzophenone hydrazone derivatives with insecticidal activity.

A broad range of benzophenone hydrazone derivatives was prepared and tested against selected chewing insect pests, allowing the analysis of structure-activity relationships. Good activity was found only when the aromatic rings were substituted at the 4-positions with an halogen atom and a triflate or perhaloalkoxy group. In contrast, a number of substituents on the hydrazone part led to active compounds, the best results being achieved with acyl-type substituents. The excellent laboratory and greenhouse activity of the best representatives was confirmed in semi-field trials against Spodoptera littoralis.

Animals↗