Synthesis, Characterization and Magnetic Hyperthermia of Monodispersed Cobalt Ferrite Nanoparticles for Cancer Therapeutics.

Magnetic nanoparticles such as cobalt ferrite are investigated under clinical hyperthermia conditions for the treatment of cancer. Cobalt ferrite nanoparticles (CFNPs) synthesized by the thermal decomposition method, using nonionic surfactant Triton-X100, possess hydrophilic polyethylene oxide chains acting as reducing agents for the cobalt and iron precursors. The monodispersed nanoparticles were of 10 nm size, as confirmed by high-resolution transmission electron microscopy (HR-TEM). The X-ray diffraction patterns of CFNPs prove the existence of cubic spinel cobalt ferrites. Cs-corrected scanning transmission electron microscopy-high-angle annular dark-field imaging (STEM-HAADF) of CFNPs confirmed their multi-twinned crystallinity due to the presence of atomic columns and defects in the nanostructure. Magnetic measurements proved that the CFNPs possess reduced remnant magnetization (MR/MS) (0.86), which justifies cubic anisotropy in the system. Microwave-based hyperthermia studies performed at 2.45 GHz under clinical conditions in physiological saline increased the temperature of the CFNP samples due to the transformation of radiation energy to heat. The specific absorption rate of CFNPs in physiological saline was 68.28 W/g. Furthermore, when triple-negative breast cancer cells (TNBC) in the presence of increasing CFNP concentration (5 mg/mL to 40 mg/mL) were exposed to microwaves, the cell cytotoxicity was enhanced compared to CFNPs alone.

Role of low-level quinolone resistance in generating tolerance in Escherichia coli under therapeutic concentrations of ciprofloxacin.

BACKGROUND: Tolerance (including persistence) and resistance result in increased survival under antibiotic pressure. OBJECTIVES: We evaluated the interplay between resistance and tolerance to ciprofloxacin under therapeutic and killing conditions to determine the contribution of low-level quinolone resistance (LLQR) mechanisms to tolerance. We also determined how the interaction between resistance (LLQR phenotypes) and tolerance was modified under SOS response suppression. METHODS: Twelve isogenic Escherichia coli strains harbouring quinolone resistance mechanisms combined with SOS response deficiency and six clinical E. coli isolates (LLQR or non-LLQR) were evaluated. Survival (tolerance or persistence) assays were used to measure surviving bacteria after a short period (up to 4 h) of bactericidal antibiotic treatment under therapeutic and killing concentrations of ciprofloxacin [1 mg/L, EUCAST/CLSI breakpoint for resistance; and 2.5 mg/L, peak serum concentration (Cmax) of this drug]. RESULTS: QRDR substitutions (S83L in GyrA alone or combined with S80R in ParC) significantly increased the fraction of tolerant bacteria (2-4 log10 cfu/mL) after exposure to ciprofloxacin at clinically relevant concentrations. The impact on tolerant bacteria due to SOS response suppression (including persistence mediated by the tisB gene) was reversed by LLQR mechanisms at therapeutic concentrations. Furthermore, no reduction in the fraction of tolerant bacteria due to SOS response suppression was observed when S83L in GyrA plus S80R in ParC were combined. CONCLUSIONS: Tolerance and quinolone resistance mutations interact synergistically, giving LLQR mechanisms an additional role in allowing bacterial survival and evasion of therapeutic antimicrobial conditions by a combination of the two strategies. At clinically relevant concentrations, LLQR mechanisms reverse further impact of SOS response suppression in reducing bacterial tolerance.

Sarcopenia, frailty and their prevention by exercise.

Sarcopenia is a major component of the frailty syndrome, both being considered as strong predictors of morbidity, disability, and death in older people. In this review, we explore the definitions of sarcopenia and frailty and summarize the current knowledge on their relationship with oxidative stress and the possible therapeutic interventions to prevent or treat them, including exercise-based interventions and multimodal strategies. We highlight the relevance of the impairment of the nervous system and of the anabolic response (protein synthesis) in muscle aging leading to frailty and sarcopenia. We also discuss the importance of malnutrition and physical inactivity in these geriatric syndromes. Finally, we propose multimodal interventions, including exercise programs and nutritional supplementation, as the strategies to prevent and treat both sarcopenia and frailty.

Urinary Tract Conditions Affect Fosfomycin Activity against Escherichia coli Strains Harboring Chromosomal Mutations Involved in Fosfomycin Uptake.

The steps by which Escherichia coli strains harboring mutations related to fosfomycin (FOS) resistance arise and spread during urinary tract infections (UTIs) are far from being understood. The aim of this study was to evaluate the effects of urine, pH, and anaerobiosis on FOS activity against a set of isogenic strains carrying the most prevalent chromosomal mutations conferring FOS resistance (ΔuhpT, ΔglpT, ΔcyaA, and ΔptsI), either singly or in combination. We also studied fosfomycin-resistant E. coli clinical isolates from patients with UTI. Our results demonstrate that urinary tract physiological conditions might have a profound impact on FOS activity against strains with chromosomal FOS resistance mutations. Specifically, acidic pH values and anaerobiosis convert most of the strains categorized as resistant to fosfomycin according to the international guidelines to a susceptible status. Therefore, urinary pH values may have practical interest in the management of UTIs. Finally, our results, together with the high fitness cost associated with FOS resistance mutations, might explain the low prevalence of fosfomycin-resistant E. coli variants in UTIs.

Hydrolytic anaerobic reactor and aerated constructed wetland systems for municipal wastewater treatment - HIGHWET project.

The HIGHWET project combines the hydrolytic up-flow sludge bed (HUSB) anaerobic digester and constructed wetlands (CWs) with forced aeration for decreasing the footprint and improving effluent quality. The HIGHWET plant in A Coruña (NW of Spain) treating municipal wastewater consists of a HUSB and four parallel subsurface horizontal flow (HF) CWs. HF1, HF2 and HF3 units are fitted with forced aeration, while the control HF4 is not aerated. All the HF units are provided with effluent recirculation, but different heights of gravel bed (0.8 m in HF1 and HF2, and 0.5 m in HF3 and HF4) are implemented. Besides, a tobermorite-enriched material was added in the HF2 unit in order to improve phosphorus removal. The HUSB 76-89% of total suspended solids (TSS) and about 40% of chemical oxygen demand (COD) and biological oxygen demand (BOD). Aerated HF units reached above 96% of TSS, COD and BOD at a surface loading rate of 29-47 g BOD5/m2·d. An aeration regime ranging from 5 h on/3 h off to 3 h on/5 h off was found to be adequate to optimize nitrogen removal, which ranged from 53% to 81%. Average removal rates of 3.4 ± 0.4 g total nitrogen (TN)/m2·d and 12.8 ± 3.7 g TN/m3·d were found in the aerated units, being 5.5 and 4.1 times higher than those of the non-aerated system. The tobermorite-enriched HF2 unit showed a distinct higher phosphate (60-67%) and total phosphorus (54%) removal.

Pharmacodynamics of fosfomycin: insights into clinical use for antimicrobial resistance.

The aim of this study was to improve the understanding of the pharmacokinetic-pharmacodynamic relationships of fosfomycin against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli strains that have different fosfomycin MICs. Our methods included the use of a hollow fiber infection model with three clinical ESBL-producing E. coli strains. Human fosfomycin pharmacokinetic profiles were simulated over 4 days. Preliminary studies conducted to determine the dose ranges, including the dose ranges that suppressed the development of drug-resistant mutants, were conducted with regimens from 12 g/day to 36 g/day. The combination of fosfomycin at 4 g every 8 h (q8h) and meropenem at 1 g/q8h was selected for further assessment. The total bacterial population and the resistant subpopulations were determined. No efficacy was observed against the Ec42444 strain (fosfomycin MIC, 64 mg/liter) at doses of 12, 24, or 36 g/day. All dosages induced at least initial bacterial killing against Ec46 (fosfomycin MIC, 1 mg/liter). High-level drug-resistant mutants appeared in this strain in response to 12, 15, and 18 g/day. In the study arms that included 24 g/day, once or in a divided dose, a complete extinction of the bacterial inoculum was observed. The combination of meropenem with fosfomycin was synergistic for bacterial killing and also suppressed all fosfomycin-resistant clones of Ec2974 (fosfomycin MIC, 1 mg/liter). We conclude that fosfomycin susceptibility breakpoints (≤64 mg/liter according to CLSI [for E. coli urinary tract infections only]) should be revised for the treatment of serious systemic infections. Fosfomycin can be used to treat infections caused by organisms that demonstrate lower MICs and lower bacterial densities, although relatively high daily dosages (i.e., 24 g/day) are required to prevent the emergence of bacterial resistance. The ratio of the area under the concentration-time curve for the free, unbound fraction of fosfomycin versus the MIC (fAUC/MIC) appears to be the dynamically linked index of suppression of bacterial resistance. Fosfomycin with meropenem can act synergistically against E. coli strains in preventing the emergence of fosfomycin resistance.

Impact of borderline minimum inhibitory concentration on the outcome of invasive infections caused by Enterobacteriaceae treated with ß-lactams: a systematic review and meta-analysis.

Minimum inhibitory concentrations (MICs) have been used to denote susceptibility in vitro and to guide clinical practice. Our objective was to investigate whether the clinical outcomes of patients with invasive infections caused by Enterobacteriaceae treated with ß-lactams were worse among those with a borderline susceptible MIC according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints than those with a lower MIC. Studies reporting MICs of ß-lactams used for infection and clinical outcome were identified through a systematic literature search. Isolates were classified as "highly susceptible" (HS, those with MIC ≤1 dilution below the susceptibility breakpoint for the antibiotic used) and "borderline susceptible" (BS, isolates with MIC at the susceptibility breakpoint) using EUCAST criteria. Clinical outcomes were clinical cure and 30-day mortality. A meta-analysis was performed. Twenty-four studies were included. Taking all antimicrobials into consideration, the meta-analysis revealed no significant difference in mortality between HS and BS [odds ratio (OR) = 0.58; 95 % confidence interval (CI): 0.28-1.21; p = 0.148). However, HS was associated with higher cure rates than BS (OR = 3.73; 95 % CI: 1.76-7.92; p < 0.001). For specific antibiotics, no differences were found except for piperacillin-tazobactam, where higher clinical cure and lower mortality rates were seen with HS compared with BS isolates (OR = 3.17; 95 % CI: 1.09-9.20; p = 0.034 and OR = 0.12; 95 % CI: 0.02-0.92; p = 0.042; respectively). Our data suggest that HS isolates are associated with higher clinical cure rates than BS isolates according to EUCAST susceptibility breakpoints; this effect was evident only for piperacillin-tazobactam, probably because of limited numbers.

Is reduced vancomycin susceptibility a factor associated with poor prognosis in MSSA bacteraemia?

OBJECTIVES: The known data about the influence of vancomycin MIC on Staphylococcus aureus bacteraemia are contradictory. Our objective was to study the possible impact of vancomycin MIC ≥1.5 mg/L on short- and medium-term mortality. METHODS: A prospective cohort study was carried out from March 2008 to January 2011 on adult patients with MSSA bacteraemia admitted to a tertiary hospital located in Seville (Spain). We studied the relationship between vancomycin MIC, accessory gene regulator (agr) type and absence of δ-haemolysin and poor prognosis. All isolates were genotyped by PFGE. Multivariate analysis, including a propensity score for having a vancomycin MIC of ≥1.5 mg/L, was performed by Cox regression. RESULTS: One hundred and thirty-five episodes of bacteraemia due to MSSA were included in the analysis. Twenty-nine (21.5%) isolates had a vancomycin MIC of ≥1.5 mg/L by Etest. There were no differences in agr distribution or absence of δ-haemolysin between isolates with reduced vancomycin susceptibility (RVS) and those without. RVS was not more frequent in specific clones; RVS was not associated with higher 14 or 30 day crude mortality (relative risk = 0.44, 95% CI = 0.14-1.35; and relative risk = 1.01, 95% CI = 0.52-1.96) rates, and it did not show higher rates of complicated bacteraemia (14.2% versus 13.8%, P = 0.61). Cox regression analysis did not significantly modify the results for 14 day mortality (HR = 0.39, 95% CI = 0.11-1.34) or 30 day mortality (HR = 0.89, 95% CI = 0.39-2.04). CONCLUSIONS: Contrary to previously published data, we did not find a relationship between RVS and higher mortality in patients with MSSA bacteraemia and we did not find a link with higher complicated bacteraemia rates.

Olive oil has a beneficial effect on impaired glucose regulation and other cardiometabolic risk factors. Di@bet.es study.

BACKGROUND: Despite the marked increase in cardiovascular risk factors in Spain in recent years, the prevalence and incidence of cardiovascular diseases have not risen as expected. Our objective is to examine the association between consumption of olive oil and the presence of cardiometabolic risk factors in the context of a large study representative of the Spanish population. SUBJECTS AND METHODS: A population-based, cross-sectional, cluster sampling study was conducted. The target population was the whole Spanish population. A total of 4572 individuals aged ≥ 18 years in 100 clusters (health centers) were randomly selected with a probability proportional to population size. The main outcome measures were clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, body mass index, waist, hip and blood pressure) and oral glucose tolerance test (OGTT) (75 g). RESULTS: Around 90% of the Spanish population use olive oil, at least for dressing, and slightly fewer for cooking or frying. The preference for olive oil is related to age, educational level, alcohol intake, body mass index and serum glucose, insulin and lipids. People who consume olive oil (vs sunflower oil) had a lower risk of obesity (odds ratio (OR)=0.62 (95% confidence interval (CI)=0.41-0.93, P=0.02)), impaired glucose regulation (OR=0.49 (95% CI=0.28-0.86, P=0.04)), hypertriglyceridemia (OR=0.53 (95% CI=0.33-0.84, P=0.03)) and low HDL cholesterol levels (OR=0.40 (95% CI=0.26-0.59, P=0.0001)). CONCLUSIONS: The results show that consumption of olive oil has a beneficial effect on different cardiovascular risk factors, particularly in the presence of obesity, impaired glucose tolerance or a sedentary lifestyle.

Prepulse inhibition predicts working memory performance whilst startle habituation predicts spatial reference memory retention in C57BL/6 mice.

Prepulse inhibition (PPI) of the acoustic startle reflex refers to the attenuation of the startle response to an intense pulse stimulus when it is shortly preceded by a weak non-startling prepulse stimulus. It is a well-established high-throughput translational measure of pre-attentive sensory gating, and its impairment is detected in several neuropsychiatric diseases including schizophrenia. It has been hypothesized that PPI might be associated with, or predictive of, cognitive deficiency in such diseases, and therefore provide an efficient assay for screening drugs with potential pro-cognitive efficacy. Free from any predetermined disease model, the present study evaluated in a homogeneous cohort of inbred C57BL/6 mice the presence of a statistical link between PPI expression and cognitive performance. Performance indices in a spatial reference memory test and a working memory test conducted in the Morris water maze, and contextual fear conditioning were correlated against pre-existing baseline PPI expression. A specific correlative link between working memory and PPI induced by weak (but not strong) prepulse was revealed. In addition, a correlation between habituation of the startle reflex and reference memory was identified for the first time: a stronger overt habituation effect was associated with superior spatial search accuracy. The PPI paradigm thus provides two independent predictors of dissociable cognitive traits in normal C57BL/6 mice; and they might serve as potential markers for high-throughput evaluation of potential cognitive enhancers, especially in the context of schizophrenia where deficits in startle habituation and PPI co-exist.

Impact of changes in CLSI and EUCAST breakpoints for susceptibility in bloodstream infections due to extended-spectrum ß-lactamase-producing Escherichia coli.

The impact of recent changes in and discrepancies between the breakpoints for cephalosporins and other antimicrobials, as determined by CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST), was analysed in patients with bloodstream infections caused by extended-spectrum ß-lactamase (ESBL) producing Escherichia coli in Spain, was analysed. We studied a cohort of 191 episodes of bloodstream infection caused by ESBL-producing E. coli in 13 Spanish hospitals; the susceptibility of isolates to different antimicrobials was investigated by microdilution and interpreted according to recommendations established in 2009 and 2010 by CLSI, and in 2011 by EUCAST. Overall, 58.6% and 14.7% of isolates were susceptible to ceftazidime, and 35.1% and 14.7% to cefepime using the CLSI-2010 and EUCAST-2009/2011 recommendations, respectively (all isolates would have been considered resistant using the previous guidelines). Discrepancies between the CLSI-2010 and the EUCAST-2011 recommendations were statistically significant for other antimicrobials only in the case of amikacin (98.4% versus 75.9% of susceptible isolates; p <0.01). The results varied depending on the ESBL produced. No significant differences were found in the percentage of patients classified as receiving appropriate therapy, following the different recommendations. Four out of 11 patients treated with active cephalosporins according to CLSI-2010 guidelines died (all had severe sepsis or shock); these cases would have been considered resistant according to EUCAST-2011. In conclusion, by using current breakpoints, extended-spectrum cephalosporins would be regarded as active agents for treating a significant proportion of patients with bloodstream infections caused by ESBL-producing E. coli.

Percepción de los estudiantes de medicina del ambiente educativo en una facultad con currículo tradicional(UCH-Chile) y otra con currículo basado en problemas (UNC-Argentina) / Medical students’ perception of the educational environment in a faculty developing a traditional curriculum (UCH-Chile) and another with a problem based learning curriculum (UNC-Argentina)

Objetivo. Evaluar y comparar la percepción que del ambiente educativo tienen los estudiantes de medicina de dos universidades iberoamericanas: Universidad de Chile (UCH) y Universidad Nacional de Cuyo (UNC), que desarrollan un currículo tradicional y un currículo basado en problemas, respectivamente. Sujetos y métodos. Participaron 465 estudiantes: 232 de la UCH y 233 de la UNC. La distribución fue de 84 y 70 estudiantes para el primer curso, 77 y 97 para el tercero, y 71 y 66 para el quinto, respectivamente. Se aplicó el cuestionario DREEM, que consiste en 50 ítems, agrupados en cinco dimensiones: percepción de la enseñanza, percepción de los profesores, autopercepción académica, percepción de la atmósfera educativa y autopercepción social. Resultados. Las puntuaciones totales fueron mayores en los tres cursos de la UNC. Resultaron similares en todos los cursos de ambas universidades, excepto en el quinto curso de la UCH. Respecto a la percepción acerca de los profesores, los estudiantes de quinto curso de la UCH mostraron las puntuaciones más bajas, mientras que los estudiantes del primer curso de la UNC tuvieron la mejor percepción. Resultados similares se obtuvieron en la autopercepción académica. La percepción del ambiente de aprendizaje fue mejor en la UNC y la autopercepción social tuvo puntuaciones similares en todos los cursos de ambas universidades. Conclusiones. Las diferencias observadas entre ambas universidades podrían atribuirse a sus diferentes currículos. El currículo basado en problemas parece ser mejor valorado que el tradicional. Nuestro estudio corrobora la eficacia del cuestionario DREEM para identificar fortalezas y debilidades del currículo y para evaluar la calidad de la enseñanza en facultades de medicina (AU)

Aim. To assess and compare the perception about the educational environment of medical students from two Latin-American universities, University of Chile (UCH) and National University of Cuyo (UNC), which develop a traditional curriculum and a problem based curriculum, respectively. Subjects and methods. A transversal study was performed in 465 students: 232 from the UCH and 233 from the UNC. The distribution was 84/70 for the first course, 77/97 for the third one and 71/66 for the fifth one, respectively. The DREEM questionnaire, which consists of 50 items, was applied. It covers 5 dimensions of the educational environment: perception about learning, perception about teachers, academic self-perception, perception about educational climate and social self-perception. Results. Total DREEM scores were significantly higher in the UNC. Scores were similar in all courses from both universities, with the exception of fifth course UCH. Regarding their perception about teachers, students of the fifth course UCH showed the lowest score, whereas students of the first course UNC had the best perception. Similar results were obtained for the academic auto-perception; while the perception of the learning environment obtained higher scores in the three courses from the UNC. Social auto-perception was similar in all courses tested in this study. Conclusions. Differences observed between both universities could be attributed to their different curricula. Problem based curriculum seems to be better appreciated than the traditional one. Our study corroborates the efficacy of the DREEM questionnaire to identify strengths and weaknesses of the curriculum and for the assessment of teaching quality in medical schools (AU)

Dos casos de sufrimiento tratados con arte terapia: una aproximación simbólica y espiritual / No disponible

Introducción: el alivio del sufrimiento sigue siendo un reto para los equipos de cuidados paliativos, incluyendo los más expertos en control de síntomas. Los aspectos emocionales y espirituales requieren una especial dedicación por parte del equipo interdisciplinar. En un enfoque holístico, el arteterapia puede ser una valiosa aliada en la búsqueda de una atención más integral. Objetivo: describimos dos casos clínicos de sufrimiento por cáncer avanzado en los cuales se suma una intervención arteterapéutica a la atención paliativa estándar de nuestra unidad. Método: las sesiones de arteterapia fueron individuales, enmarcadas en un vínculo seguro paciente-terapeuta y con una orientación de revisión biográfica. La creación propia de trabajos artísticos (dibujo, pintura, collage, moldeado, escritura creativa) ofrece al paciente la oportunidad de descubrir e interpretar claves simbólicas y estéticas sobre su mundo interior, válidas para responder a sus necesidades emocionales y espirituales. Resultados: ambas personas acompañadas en su proceso arteterapéutico encontraron en sus obras elementos esenciales de sus respectivas maneras de afrontar el sufrimiento. Destacamos por ejemplo la adquisición de una mayor sensación de control, la conexión con la fe religiosa o el ser más consciente de la importancia del "aquí-y-ahora". Conclusión: observamos que los beneficios aportados a los pacientes por la experiencia en arteterapia contribuyen a mejorar su calidad de vida y comunicación e indirectamente las de sus familiares, con la consiguiente valoración positiva por parte del equipo interdisciplinar (AU)

Introduction: Relief of suffering continues to be a challenge for palliative care teams, including those most experienced in symptom control. Emotional and spiritual aspects need special dedication from the interdisciplinary team. In a holistic approach, art therapy can be a valuable allied health discipline to achieve a more comprehensive care. Objective: We describe two case histories of suffering caused by terminal cancer in which we provided art therapy as well as standard palliative care. Method: Art therapy sessions were individual, framed in a safe patient therapist link, and with an orientation to biographical review. The creation of art works (drawing, painting, collage, claying, creative writing) gives the patient a chance to discover and interpret symbolic and esthetic keys from his inner world. This may be a way to cope with emotional and spiritual needs. Results: During their art therapy process, patients found in their works essential elements about the proper way to cope with suffering, increasing a sense of control, connecting with religious faith, or increasing insight into the importance of the "here-and-now" reality concept. Conclusion: We observed that art therapy outcomes contribute to improved quality of life and communication. These lead to increased family wellbeing. Consequently, art therapy is positively valued by the interdisciplinary team (AU)

Activity of ciprofloxacin and levofloxacin in experimental pneumonia caused by Klebsiella pneumoniae deficient in porins, expressing active efflux and producing QnrA1.

The objective of this study was to evaluate the activities of ciprofloxacin and levofloxacin in a murine model of pneumonia caused by Klebsiella pneumoniae C2 (with altered GyrA, deficient in porins and expressing active efflux of quinolones) and the transconjugant C2pMG252 derived from it and expressing the qnrA1 determinant. MICs and MBCs of the two quinolones were determined according to CLSI guidelines. Time-kill curves (at 1x and 4x MIC) were also performed to assess bactericidal activity. An experimental model of pneumonia in mice was evaluated. Groups of 15 mice were infected with either strain and treated with ciprofloxacin (80 mg/kg/day) or levofloxacin (100 mg/kg/day). Control non-treated animals were also evaluated. In the case of strain C2, log(10) CFU/g of lung in non-treated animals was 9.16 +/- 2.16. This value was reduced to 3.53 +/- 1.04 (p <0.001) and 3.38 +/- 0.46 (p <0.001) in animals treated with ciprofloxacin or levofloxacin, respectively. Percentages of surviving mice were 26.7% (control group) and 100% (both ciprofloxacin and levofloxacin; p <0.001 vs. controls). Bacterial counts (log(10) CFU/g) in lungs of animals infected with strain C2pMG252 were 9.65 +/- 2.49 in non-treated animals and 7.74 +/- 2.67 and 7.57 +/- 3.84 for those treated with ciprofloxacin or levofloxacin, respectively (p >0.05 vs. control group). Of non-treated animals infected with strain C2pMG252, 14.3% survived. Ciprofloxacin and levofloxacin improved the survival in these mice (53.3% for both antimicrobials, p 0.03). In conclusion, the expression of qnrA1 in K. pneumoniae with additional mechanisms of resistance causes decreased efficacy of fluoroquinolones in a pneumonia model in mice.

Efficacy of amoxycillin-clavulanate in an experimental model of murine pneumonia caused by AmpC-non-hyperproducing clinical isolates of Escherichia coli resistant to cefoxitin.

The algorithms included in most automated systems used for antimicrobial susceptibility testing (e.g., Vitek 2) consider that Escherichia coli isolates resistant to cefoxitin are AmpC-hyperproducers and, consequently, resistant also to amoxycillin-clavulanate. However, a recent study revealed that 30% of E. coli clinical isolates resistant to cefoxitin remained susceptible in vitro to amoxycillin-clavulanate. The aim of the present study was to evaluate the in-vivo efficacy of amoxycillin-clavulanate in the treatment of an experimental model of pneumonia, using two clonally related isolates (with identical repetitive extragenic palindromic sequence (REP)-PCR patterns) of AmpC-non-hyperproducing and OmpF-lacking E. coli (Ec985 and Ec571) that were resistant to cefoxitin and susceptible to cefotaxime and amoxycillin-clavulanate. MICs were determined using a microdilution technique, and in-vitro bactericidal activity was tested using time-kill assays. The in-vivo efficacy of amoxycillin, amoxycillin-clavulanate and cefotaxime against both isolates was tested in a murine pneumonia model using immunocompetent C57BL/6 mice. Ec571 (a TEM-1/2 producer) was resistant to amoxycillin, whereas Ec985 (a TEM-1/2 non-producer) was susceptible. Amoxycillin, amoxycillin-clavulanate and cefotaxime were bactericidal for Ec985, and amoxycillin-clavulanate and cefotaxime were bactericidal for Ec571 at different concentrations and time-points, as determined using time-kill assays. Treatment with amoxycillin, amoxycillin-clavulanate and cefotaxime reduced the bacterial lung concentration of Ec985 compared with non-treated controls (p <0.05), whereas amoxycillin-clavulanate and cefotaxime showed efficacy against Ec571 when compared with the control and amoxycillin groups (p <0.05). Regardless of the exact underlying mechanism(s) of resistance, amoxycillin-clavulanate was effective in the experimental murine model in the treatment of pneumonia caused by AmpC-non-hyperproducing strains of E. coli resistant to cefoxitin.

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.

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.

Clinical efficacy and safety of a depigmented and glutaraldehyde polymerized therapeutic vaccine of Parietaria judaica.

BACKGROUND: The inhalation of Parietaria judaica pollen is a common cause of allergic respiratory diseases in the Mediterranean area. The objective of this study was to investigate the safety and clinical efficacy of a chemically modified (depigmented and glutaraldehyde-polymerized) vaccine of Parietaria judaica. METHODS AND RESULTS: Thirty patients with a well-documented clinical history of seasonal rhinitis and clinical sensitivity to Parietaria judaica pollen were included in a randomized trial during 12 months. The study was conducted following good clinical practices and appropriate consent forms were signed. Patients were divided into 2 groups of 15 individuals; group A received the modified extract and group C did not receive specific immunotherapy. Any adverse event was recorded to assess safety. Symptom scores, symptomatic medication use and the results of specific nasal challenges (before and after 12 months of treatment) were recorded to evaluate clinical efficacy. The treatment schedule consisted of an incremental phase of 5 injections and a maintenance dosage of 0.5 ml per month. Each patient received 14 injections during this period. All the patients completed the trial and no adverse reactions related to immunotherapy were recorded. A significant difference (p < 0.001) in symptom scores and overall use of symptomatic medication was observed between the two groups, being both scores lower in group A. No significant differences in nasal sensitivity existed before treatment among the 2 groups. However, after 12 months, a significant difference (p < 0.05) was observed only in group A patients, who showed a significant improvement in specific nasal challenges. CONCLUSIONS: Immunotherapy with depigmented and glutaraldehyde-polymerized extract of Parietaria judaica pollen is safe and effective to treat patients with allergic rhinitis and clinical sensitivity to this pollen.

Clinical efficacy and safety of a depigmented and glutaraldehyde polymerized therapeutic vaccine of Parietaria judaica

Background: The inhalation of Parietaria judaica pollen is a common cause of allergic respiratory diseases in the Mediterranean area. The objective of this study was to investigate the safety and clinical efficacy of a chemically modified (depigmented and glutaraldehyde-polymerized) vaccine of Parietaria judaica. Methods and results: Thirty patients with a well-documented clinical history of seasonal rhinitis and clinical sensitivity to Parietaria judaica pollen were included in a randomized trial during 12 months. The study was conducted following good clinical practices and appropriate consent forms were signed. Patients were divided into 2 groups of 15 individuals; group A received the modified extract and group C did not receive specific immunotherapy. Any adverse event was recorded to assess safety. Symptom scores, symptomatic medication use and the results of specific nasal challenges (before and after 12 months of treatment) were recorded to evaluate clinical efficacy. The treatment schedule consisted of an incremental phase of 5 injections and a maintenance dosage of 0.5 ml per month. Each patient received 14 injections during this period. All the patients completed the trial and no adverse reactions related to immunotherapy were recorded. A significant difference (p < 0.001) in symptom scores and overall use of symptomatic medication was observed between the two groups, being both scores lower in group A. No significant differences in nasal sensitivity existed before treatment among the 2 groups. However, after 12 months, a significant difference (p < 0.05) was observed only in group A patients, who showed a significant improvement in specific nasal challenges. Conclusions: Immunotherapy with depigmented and glutaraldehyde-polymerized extract of Parietaria judaica pollen is safe and effective to treat patients with allergic rhinitis and clinical sensitivity to this pollen (AU)

Antecedentes: La inhalación del polen de Parietaria judaica es una causa frecuente de enfermedades respiratorias alérgicas en la región mediterránea. El objetivo de este estudio era investigar la seguridad y la eficacia clínica de una vacuna químicamente modificada (despigmentada y polimerizada con glutaraldehído) de Parietaria judaica. Métodos y resultados: Se incluyó en un estudio aleatorizado de 12 meses de duración a 30 pacientes con historia clínica bien documentada de rinitis estacional y sensibilidad clínica al polen de Parietaria judaica. El estudio se llevó a cabo conforme a las buenas prácticas clínicas y se firmaron los formularios de consentimiento apropiados. Se distribuyó a los pacientes en dos grupos de 15 sujetos; el grupo A recibió el extracto modificaco y el grupo C no recibió inmunoterapia específica. Para evaluar la inocuidad se registraron las reacciones adversas. Para evaluar la eficacia clínica se registraron las puntuaciones de los síntomas, el uso de medicación sintomática y los resultados de pruebas de provocación nasales específicas (antes y después de 12 meses de tratamiento).El régimen de tratamiento consistió en una fase de incremento de 5 inyecciones y una posología de mantenimiento de 0,5 ml al mes. Cada paciente recibió 14 inyecciones durante ese período. Todos los pacientes se sometieron al ensayo completo y no se registraron reacciones adversas relacionadas con la inmunoterapia. Se observó una diferencia significativa (p < 0,001) en las puntuaciones de los síntomas y el uso global de medicación sintomática entre los dos grupos; ambas puntuaciones fueron menores en el grupo A. Antes del tratamiento no se observaron diferencias significativas en la sensibilidad nasal de los dos grupos. Sin embargo, al cabo de 12 meses, se observó una diferencia considerable (p < 0,05) sólo en los pacientes del grupo A, los cuales experimentaron una mejoría significativa en pruebas de provocación nasales específicas. Conclusiones: La inmunoterapia con extracto despigmentado y polimerizado con glutaral de hído de polen de Parietaria judaica es segura y eficaz para tratar a los pacientes con rinitis alérgica y sensibilidad clínica a este polen (AU)