Urgent need for a rapid microbiological diagnosis in critically ill pneumonia.

Severe lower respiratory tract infection is a common issue in Intensive Care Units that causes significant morbidity and mortality. The traditional diagnostic-therapeutic approach has been grounded on taking respiratory samples and/or blood cultures as soon as possible and starting empirical antibiotic therapy addressed to cover most likely pathogens based on the presence of the patient's risk factors for certain microorganisms, while waiting for the culture results in the following 48-72 hours to adequate the antibiotic treatment to the sensitivity profile of the isolated pathogen. Unfortunately, this strategy leads to use broad-spectrum antibiotics more times than necessary and does not prevent possible therapeutic failures. The recent development of rapid molecular diagnostic techniques, based on real time polymerase chain reaction (RT-PCR), makes it possible to determine the causative agent and its main resistance pattern between 1 and 5 hours after sampling (depending on each tecnique), with high precision, some of them reaching a negative predictive value greater than 98%, facilitating the very early withdrawal of unnecessary broad-spectrum antibiotics. Its high sensitivity can also detect unsuspected pathogens based on risk factors, allowing adequate treatment in the first hours of stay. This short review discusses the potential usefulness of these techniques in critically ill patients with lower respiratory tract infection and advocates their immediate implementation in clinical practice.

Reactivación silenciosa del virus de la hepatitis B en paciente que reinicia diálisis tras trasplante renal. ¿Cómo podemos prevenirlo o anticiparlo en el diagnóstico? / Reactivation of hepatitis B virus in patient that rests dialysis after renal transplantation. How can we prevent it or anticipate it in diagnosis?

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Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry).

BACKGROUND: Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. OBJECTIVES: This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. METHODS: This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. RESULTS: A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). CONCLUSION: SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

Basophils Trigger Fibroblast Activation in Cardiac Allograft Fibrosis Development.

Fibrosis is a major component of chronic cardiac allograft rejection. Although several cell types are able to produce collagen, resident (donor-derived) fibroblasts are mainly responsible for excessive production of extracellular matrix proteins. It is currently unclear which cells regulate production of connective tissue elements in allograft fibrosis and how basophils, as potential producers of profibrotic cytokines, are involved this process. We studied this question in a fully MHC-mismatched model of heart transplantation with transient depletion of CD4(+) T cells to largely prevent acute rejection. The model is characterized by myocardial infiltration of leukocytes and development of interstitial fibrosis and allograft vasculopathy. Using depletion of basophils, IL-4-deficient recipients and IL-4 receptor-deficient grafts, we showed that basophils and IL-4 play crucial roles in activation of fibroblasts and development of fibrotic organ remodeling. In the absence of CD4(+) T cells, basophils are the predominant source of IL-4 in the graft and contribute to expansion of myofibroblasts, interstitial deposition of collagen and development of allograft vasculopathy. Our results indicated that basophils trigger the production of various connective tissue elements by myofibroblasts. Basophil-derived IL-4 may be an attractive target for treatment of chronic allograft rejection.

Hemodiálisis 4 díasa la semana: una alternativa eficaz en el control de la tensión arterial y en alcanzarel peso objetivo posterior a la diálisis / No disponible

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Respuesta clínica al tratamiento con iloprost en paciente con enfermedad por ateroembolismo de colesterol / No disponible

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Non-typhi Salmonella infection in patients with rheumatic diseases on TNF-alpha antagonist therapy.

OBJECTIVES: The morbidity and mortality of patients with rheumatic diseases has improved considerably following the use of biologic therapies. However, an increase in the frequency of bacterial infections has been observed in patients receiving these drugs. In the present study we aimed to establish the incidence and clinical manifestations of non-typhi Salmonella infection in a large cohort of patients with rheumatic diseases undergoing TNF-alpha antagonist therapy due to severe rheumatic diseases refractory to conventional therapies. METHODS: The rate of non-typhi Salmonella infection found in the Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases (BIOBADASER) was compared with that observed in a cohort of rheumatoid arthritis (RA) patients from the EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) Study, who were not treated with TNF-alpha antagonists. The rate found in the BIOBADASER registry was also compared with that available in a non-RA historic control cohort reported in a population from Huesca (Northern Spain). RESULTS: Seventeen cases of non-typhi Salmonella infection were observed in the series of patients exposed to anti-TNF-alpha therapies. The incidence rate of non-typhi Salmonella in BIOBADASER was 0.73 per 1000 patient-years (95% confidence interval [CI]: 0.45-1.17). The incidence rate in the EMECAR cohort was 0.44 per 1000 patient-years. The relative risk for non-typhi salmonellosis in RA patients exposed to TNF-alpha inhibitors compared to those not treated with biological therapies was 2.07 (95% CI: 0.27-15.73) (p=0.480) whereas the relative risk of non-typhi Salmonella infections in patients with rheumatic diseases undergoing TNF-alpha antagonist therapy compared with the non-RA Spanish control cohort was 0.63 (95% CI: 0.38-1.04) (p=0.07). Nine of the 17 patients with non-typhi salmonellosis presented a severe systemic infection. CONCLUSION: Incidence of non-typhi Salmonella infection is not increased significantly in rheumatic patients undergoing anti-TNF-alpha therapy when compared with RA patients undergoing conventional DMARD therapy or with the general population. Nevertheless, at least 50% of patients on TNF-alpha have severe complications once they develop non-typhi Salmonella infection. This fact suggests that anti-TNF-alpha therapies may predispose to salmonella dissemination rather than to infection.

Influence of the metabolic profile on the in vivo antioxidant activity of quercetin under a low dosage oral regimen in rats.

BACKGROUND AND PURPOSE: Flavonoids are known to possess a broad set of pharmacological effects, some of which have been attributed to their antioxidant properties and, more recently, to cell signalling modulation. Nevertheless, flavonoids are extensively metabolized and their metabolites are the potential bioactive forms in vivo. Therefore, a first and crucial step to understand the mechanisms underlying potential health benefits of flavonoids is knowledge of their metabolites and their biological activities. EXPERIMENTAL APPROACH: To approximate a human dietary pattern of intake of flavonoids, regular rat chow was supplemented with 0.02% quercetin and fed to Sprague-Dawley rats over 3 weeks. Plasma samples were analysed by HPLC and electrospray tandem mass spectrometry, and plasma antioxidant capacity was measured by the 2,2'-azino-bis(3-ethylbenzothiazoline sulphonate) assay. KEY RESULTS: Major metabolites were 3'-methylquercetin (isorhamnetin) glucuronide sulphate conjugates, the most plausible conjugation positions being at the 3-, 5- and 7-hydroxyl positions. Isorhamnetin conjugates are methylated at the 3'-OH position, which decreases the high antioxidant activity of quercetin and its metabolites and their contribution to plasma antioxidant potential. CONCLUSIONS AND IMPLICATIONS: This metabolic pattern differs from that observed after a single high-dose administration, where the major metabolites were quercetin conjugates at 5- and 7-hydroxyl positions and a significantly increased plasma antioxidant activity was observed. These data show altogether that the different metabolic patterns obtained under a prolonged low-dosage regimen or after a single high dose, crucially affected the antioxidant potential of plasma in treated animals. Our data also allow for the establishment of structure-antioxidant activity relationships for quercetin metabolites.

Determination of methotrexate, several pteridines, and creatinine in human urine, previous oxidation with potassium permanganate, using HPLC with photometric and fluorimetric serial detection.

A novel HPLC method, using UV and fluorimetric serial detection, for the simultaneous determination of methotrexate (MTX), five disease marker pteridines, and the reference metabolic subproduct creatinine (CREA) in human urine was established. A previous oxidation process using 10(-3) M KMnO4 (pH 5.0) and 35min of oxidation time was necessary to transform the analytes in the highly fluorescent pteridinic rings. CREA was not affected by the oxidative medium. Using Tris-HCl/NaCl buffer solution (pH 6.6) as mobile phase, MTX and the assayed pteridines were monitored by fluorescence at lambda(em) = 444 nm and lambda(ex) = 280 nm and creatinine was monitored by absorption measurements at lambda(abs) = 230 nm. All components were well resolved in approximately 7 min. Detection limits, according the criteria of Clayton and co-workers, were 10 ng ml(-1) for MTX, less than 1 ng ml(-1) for all of the pteridines, and 4 microg ml(-1) for CREA.

Artropatía ocronótica. Caso clínico / Ochronotic arthropathy. A case report

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Prevalence of HLA-B27 and subtypes of HLA-B27 associated with ankylosing spondylitis in Galicia, Spain.

OBJECTIVE: To assess the prevalence of HLA-B27 and its subtypes in both the normal population and in patients with Ankylosing Spondylitis (AS) in Galicia, Northwest Spain. METHODS: The prevalence of HLA-B27 in the normal population was determined by checking the number of HLA-B27 positive samples in 308 subjects from different areas of Galicia who had donated organs over a period of 4 years. A total of 106 patients with the diagnosis of AS, according to the modified New York clinical criteria for definitive ankylosing spondylitis, were collected from three very representative areas of Galicia. HLA-B27 was determined by PCR using the primers E91s and E136as, while 11 subtypes of HLA-B27 were analyzed using a commercial kit. RESULTS: The prevalence of HLA-B27 in organ donors was 9.34%. HLA-B27 was present in 94.3% of patients with AS. Subtypes B*2701, B*2709 and B*2710 were not found. The subtypes found in the normal population were; B*2705 (79.5%), B*2702 (18%) and B*2708 (2.5%). The subtypes associated with AS were B*2705 (88%) and B*2702 (12%). CONCLUSION: The prevalence of HLA-B27 in Galicia was 9.34%, which is higher than previously published in Spain. The frequency of the subtypes associated with AS was similar to that reported for other Spanish regions.

Valoración del grado de satisfacción de los familiares de pacientes ingresados en una unidad de cuidados intensivos / Evaluation of satisfaction among the relatives of patients admitted to an intensive care unit

Objetivo. Valorar el grado de satisfacción de los familiares de los pacientes ingresados en una unidad de cuidados intensivos (UCI) respecto al entorno asistencial y a la información recibida, motivando la reflexión sobre la atención prestada y analizando los procesos susceptibles de mejora.Diseño. Estudio prospectivo, descriptivo durante un período de 4 meses. Ámbito. UCI polivalente del Hospital Universitario 12 de Octubre de Madrid. Pacientes. Pacientes adultos ingresados en la UCI y que fueron dados de alta a planta de hospitalización. Intervención. Se diseñó una encuesta con 40 preguntas que se distribuyó a los familiares de primer grado de los pacientes a los 15 días del alta de la unidad. La recogida de los datos se efectuó mediante entrevista personal o telefónica.Variables de interés principales. En la encuesta se recogieron datos demográficos; motivo de ingreso y sus complicaciones durante el éste; condiciones medioambientales (intimidad, ruidos, mobiliario, sala de espera, limpieza, etc.); relación con el personal médico y la calidad de la información que había recibido; relación con el personal de enfermería (información sobre los cuidados y las normas de la UCI); y, por último, la organización y los tiempos de la visita. Resultados. Se incluyó en el estudio a 55 pacientes. Los motivos más frecuentes de ingreso fueron: insuficiencia respiratoria grave, 33,3 por ciento; patología neurológica, 33,3 por ciento, y sepsis de diverso origen, 21,6 por ciento. El tiempo medio (DE) de estancia en la UCI fue de 8,8 (8) días. Respecto a las condiciones medioambientales, se detectó la necesidad de una sala de espera acondicionada y una sala de información más amplia e iluminada. El 98 por ciento de los encuestados consideró óptimos la limpieza y el orden de la UCI. El nivel de ruido y la iluminación ambientales se valoraron positivamente. El 89 por ciento de los encuestados consideró la información médica diaria clara y el 82 por ciento, adecuado el horario de información. La información diaria acerca de los procesos de cuidados de enfermería se valoró como fluida y adecuada. Se detectó un elevado porcentaje de respuestas que indicaban la necesidad de ampliar el tiempo de permanencia con su familiar.Conclusiones. La relación del personal sanitario con los familiares de los pacientes fue valorada positivamente, pero los resultados detectaron la necesidad de realizar mejoras estructurales en la UCI y modificar el régimen de visita (AU)

Comparison of UV derivative-spectrophotometry and partial least-squares (PLS-1) calibration for determination of methotrexate and leucovorin in biological fluids.

Binary mixtures of methotrexate (MTX) and leucovorin (LV) have been resolved by application of first-derivative spectrophotometry and partial least squares calibration (PLS-1). By measuring the first-derivative signals of MTX and LV at 354 and 300 nm, respectively, simultaneous determination was possible. The mean recoveries for urine samples were 91 and 96% for MTX and LV, respectively. Partial least squares (PLS-1) multivariate calibration has been applied to the determination of these compounds in serum and in urine without pretreatment of the samples. The absorption spectra of serum or urine samples spiked with methotrexate and/or leucovorin, were used to optimize the calibration matrixes by the PLS-1 method. The sensitivity and selectivity of the proposed procedures were calculated. Mean recoveries were 101 and 97% for MTX and LV, respectively, for serum samples, and 101 and 98% for MTX and LV, respectively, for urine samples.

Tuberculous spondylitis: epidemiologic and clinical study in non-HIV patients from northwest Spain.

OBJECTIVES: To study the epidemiology, clinical features, and outcome of non-human immunodeficiency virus (HIV) patients diagnosed with tuberculous spondylitis (TS) in a well-defined region of northwestern Spain. METHODS: Retrospective chart review of patients older than 14 years of age diagnosed with TS at two contiguous areas between 1986 and 1999. RESULTS: Thirty-seven patients (19 men; mean age 60.3 years) were diagnosed with TS. The average annual incidence rate of TS was 0.55/100,000 population 15 years of age and older. The thoracic and lumbar regions were affected in most cases. The mean duration of symptoms before diagnosis was 28 weeks (range 3-129). Active or healed pulmonary tuberculosis was observed in only 30%. The tuberculin skin test was negative in 24%. The most common findings at the time of diagnosis were back pain and elevated ESR (either 89%). Of note, only 19% had fever. On admission plain radiographs disclosed the presence of spondylitis in 84% of the patients. Computed tomography scan and magnetic resonance imaging yielded conclusive diagnostic data in the cases with normal radiographs, and were very useful in the visualization of abscesses and intraspinal compression. Cultures of material from percutaneous needle aspiration and open bone biopsy were positive for Mycobacterium tuberculosis in 79% and 77% of the cases, respectively. Antituberculous therapy was given to all patients (mean duration of treatment 44 weeks). Surgical procedures were performed in 12 cases, in 7 of them to remove paraspinal and/or epidural abscesses, and in 5 because of neurological complications. Local pain and neurological deficits were the mostfrequent sequelae (16 and 8 cases, respectively). One patient died during the course of treatment due to a co-morbid disease. None of the patients had relapses of tuberculosis. CONCLUSION: TS is a major cause of morbidity. There is a long delay to the diagnosis in most patients. Awareness of its clinical features and early therapy are required to reduce severe complications.

Determination of triamterene and leucovorin in biological fluids by UV derivative-spectrophotometry and partial least-squares (PLS-1) calibration.

The resolution of binary mixtures of triamterene (TAT) and leucovorin (LV) by application of first-derivative spectrophotometry and by application of Partial Least Squares calibration (PLS-1) was performed. Triamterene is determined in presence of leucovorin directly in the absorption spectra at 358 nm, and leucovorin is determined in the first-derivative spectra at 305.6 nm, zero-crossing of the triamterene. The mean recovery values in urine samples were 102 and 97% for TAT and LV, respectively. Partial Least Squares calibration (PLS-1) multivariate calibration of spectrophotometric data, have been applied to the determination of these compounds in serum and in urine without pretreatment of the samples. The absorption spectra of samples of serum or urine, spiked with triamterene and/or leucovorin, were used to perform the optimization of the calibration matrices by PLS-1 method. Mean recovery values were of 107 and 108% for TAT and LV in serum samples, and 98 and 91% for TAT and LV in urine samples.

Selection of the wavelength range and spectrophotometric determination of leucovorin and methotrexate in human serum by a net analyte signal based method.

Leucovorin (LV) and methotrexate (MTX) were determined in human blood serum samples by using a model based in the net analytical signal concept. The calibration method used is a variation of the original hybrid linear analysis (HLA) method, developed by Goicoechea and Olivieri (HLA/GO). The calibration set was composed by nine serum samples with different amounts of LV and MTX in the range of 0-10 mugml(-1). The selection of the optimum wavelength range involved the calculation of the net analyte signal regression plot for each test sample, in conjunction with the calculation of the minimum error indicator. Relative errors of prediction (REP, %) of 3.0 and 5.3% were calculated for LV and MTX, respectively. Only two factors were necessary to optimize the proposed HLA/GO model. Sensitivity, selectivity, analytical sensitivity and limit of detection of the proposed procedure were calculated. Detection limits of 0.34 and 0.93 mugml(-1) for LV and MTX were determined. The proposed model was tested in the analysis of serum samples, without previous separation steps, obtaining recovery values between 96 and 99%, and between 92 and 103% for LV and MTX, respectively.