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Biomedical subjects

M A Marcos

Publications and source records attributed to M A Marcos.

At least 19 recordsLinked to original sources

Effectiveness of virosomal subunit influenza vaccine in preventing influenza-related illnesses and its social and economic consequences in children aged 3-14 years: a prospective cohort study.

To evaluate the effectiveness of a virosomal subunit influenza vaccine in preventing influenza-related illnesses and its social and economic consequences in children aged 3-14 years, a prospective cohort study was carried out during the 2004-2005 influenza season in 11 private pediatric clinics in the Barcelona metropolitan area. One dose of a virosomal subunit inactivated influenza vaccine (Inflexal V Berna) was given during September and October 2004 to healthy children aged 3-14 years attended in 5 of the 11 clinics. Who comprised the vaccinated cohort (n=966). The non-vaccinated cohort (n=985) was comprised of children attended in the other six clinics. Informed consent was obtained from all parents. The follow up was performed between 1 November 2004 and 31 March 2005. Using a self-administered questionnaire, information was collected from parents or guardians on any type of acute, febrile respiratory illness suffered by their children during the study period, including antibiotic use, and absence from school or work-loss of parents as a result of the illness. RT-PCR (influenza A+B+C) was carried out on pharyngeal and nasal samples obtained from children attended by pediatricians during this period in these clinics with the following symptoms: fever> or =38.5 degrees lasting at least 72h, cough or sore throat (influenza-like illness). Adjusted vaccination effectiveness was 58.6% (95% CI 49.2-66.3) in preventing acute febrile respiratory illnesses, 75.1% (95% CI 61.0-84.1) in preventing cases of influenza-like illnesses and 88.4% (95% CI 49.2-97.3) in preventing laboratory-confirmed cases of influenza A. The adjusted vaccination effectiveness in reducing antibiotic use (18.6%, 95% CI -4.2 to 3.64), absence from school (57.8%, 95% CI 47.9-65.9) and work-loss of parents (33.3%, 95% CI 8.9-51.2) in children affected by an acute febrile respiratory illness was somewhat lower. Vaccination of children aged 3-14 years in pediatric practices with one dose of virosomal subunit inactivated influenza vaccine has the potential to considerably reduce the health and social burdens caused by influenza-related illnesses.

Adolescent↗

Mixed community-acquired pneumonia in hospitalised patients.

The role of mixed community-acquired pneumonia (CAP) is controversial. The aim of the present study was to determine the incidence, principal microbial patterns, clinical predictors and course of mixed CAP. The current study included 1,511 consecutive hospitalised patients with CAP. Of these, 610 (40%) patients had an established aetiology. One pathogen was demonstrated in 528 patients and 82 (13%) patients had mixed pneumonia. Cases including CAP, by a pyogenic bacteria and a complete paired serology for "atypicals", revealed that 82 (13%) patients had definite single pyogenic pneumonia and 28 patients (5%) had mixed pyogenic pneumonia. In patients with mixed CAP, Streptococcus pneumoniae was the most prevalent microorganism (44 out of 82; 54%). The most frequent combination was S. pneumoniae with Haemophilus influenzae (17 out of 82; 21%). Influenza virus A and S. pneumoniae (five out of 28; 18%) was the most frequent association in the mixed pyogenic pneumonia group. No clinical predictors for mixed pneumonias could be identified. Patients with mixed pyogenic pneumonia more frequently developed shock when compared with patients with single pyogenic pneumonia (18 versus 4%). In conclusion, mixed pneumonia occurs in >10% of cases with community-acquired pneumonia requiring hospitalisation.

Adolescent↗

Lower mortality among patients with community-acquired pneumonia treated with a macrolide plus a beta-lactam agent versus a beta-lactam agent alone.

A cohort of 1,391 patients with community-acquired pneumonia of unknown etiology, atypical pneumonia, Legionella pneumophila pneumonia, viral pneumonia, or pneumococcal pneumonia was studied according to a standard protocol to analyse whether the addition of a macrolide to beta-lactam empirical treatment decreases mortality rates. Patients admitted to the intensive care unit were excluded. Severity was assessed using the PORT score. An etiological diagnosis was achieved in 498 (35.8%) patients (292 infections due to Streptococcus pneumoniae). Treatment was chosen by the attending physician according to his/her own criteria: beta-lactam agent in 270 and beta-lactam agent plus a macrolide in 918 cases. The mortality rate was 13.3% in the group treated with a beta-lactam agent alone and 6.9% in the group treated with a beta-lactam agent plus a macrolide (p=0.001). The percentage of PORT-group V patients was 32.6% in the group treated with a beta-lactam agent alone compared to 25.7% in the group who received a beta-lactam agent plus a macrolide (p=0.02). After controlling for PORT score, the odds of fatal outcome was two times higher in patients treated with a beta-lactam agent alone than in those treated with a beta-lactam agent plus a macrolide (adjusted OR = 2, 95%CI 1.24-3.23). The results suggest that the addition of a macrolide to an initial beta-lactam-based antibiotic regimen is associated with lower mortality in patients with community-acquired pneumonia, independent of severity of infection, thus supporting the recommendation of a beta-lactam-agent plus a macrolide as empirical therapy.

Amoxicillin-Potassium Clavulanate Combination↗

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↗

Rapid urinary antigen test for diagnosis of pneumococcal community-acquired pneumonia in adults.

Streptococcus pneumoniae is suspected to cause an important proportion of community-acquired pneumonia (CAP) whose aetiology cannot be detected with conventional tests. In this study, the authors evaluated the diagnostic yield of a new immunochromatographic membrane test (ICT) for the detection of the S. pneumoniae antigen in the urine of patients admitted with diagnosed CAP. ICT was performed in unconcentrated and concentrated urine from all the patients. ICT was repeated 1 month after discharge in a group initially testing positive. The authors also studied the ICT in clinically stable human immunodeficiency virus type 1 (HIV1)-infected patients. S. pneumoniae antigen was detected in all of the 68 (100%) patients tested with definitive pneumococcal pneumonia. In five of these cases ICT was only positive when it had been performed on the patients. The S. pneumoniae antigen was also detected in 36 (69.2%) of 52 patients with probable pneumococcal pneumonia and in 50 of 277 (18%) patients without pneumococcal pneumonia. ICT remained positive in 16 (69.5%) of 23 patients, 1 month after hospital discharge. Nasopharyngeal colonisation with S. pneumoniae was detected in 8 (12%) of 68 clinically stable HIV1 infected patients, but none tested ICT positive. The Binax NOW it immunochromatographic membrane test is a rapid, sensitive and specific test for detecting pneumococcal community-acquired pneumonia in adults. The test may remain positive for several weeks after pneumococcal pneumonia.

Acquired Immunodeficiency Syndrome↗

C-reactive protein levels in community-acquired pneumonia.

The diagnostic value of C-reactive protein (CRP) admission serum levels as an indicator of the aetiology of community-acquired pneumonia (CAP) was evaluated. A cohort of 1,222 patients with CAP was assessed. CRP levels were analysed in 258 patients with a single aetiological diagnosis. The mean CRP values in patients with pyogenic, atypical, viral and Legionella pneumophila pneumonia were: 16 mg x dL(-1), 13 mg x dL(-1), 14 mg x dL(-1) and 25 mg x dL(-1), respectively. CRP levels were not significantly different among patients outcome research team (PORT) groups (19 mg x dL(-1) in groups I-II, 16 mg x dL(-1) in group III and 16 mg x dL(-1) in groups IV-V). A cut-off point of 25 mg x dL(-1) had a sensibility, specificity, positive predictive value and negative predictive value of 0.6, 0.83, 0.3, and 0.94, respectively. After controlling for age and PORT score, the odds of having a CRP level >25 mg x dL(-1) was 6.9 times higher in patients with L. pneumophila pneumonia than in those with non-L. pneumophila pneumonia. Patients with Legionella pneumophila pneumonia had higher C-reactive protein levels than those with pneumonia of any other aetiology, independently of severity of infection. Being a cheap and readily available test, C-reactive protein may be a useful adjunctive procedure in the diagnosis of community-acquired pneumonia.

Aged↗

[Glutathione-related enzymes activity during vitrectomy. Effect of BSS Plus(R) in retinal tissue].

PURPOSE: To determine changes in the retinal activity of two enzymes related to the glutathione metabolism (Glutathione synthetase -GSHS- and glutathione reductase -GSSGR-) after vitrectomy using BSS Plus(R). MATERIAL AND METHODS: Forty-five pigmented rabbits were distributed in 6 groups: group I (GSHS control in retinal tissue); Group II (analysis of GSHS at 3 hours post-vitrectomy); Group III (determination of GSHS at 48 hours after vitrectomy); Group IV (GSSGR control in retinal tissue); Group V (measurement of GSSGR at 3 hours post-surgery) and Group VI (study of GSSGR at 48 hours post-vitrectomy). Statistical analysis was done by a parametric test (ANOVA of single factor) (p<0.05). RESULTS: The activity of these enzymes was: Group I (n=5, basal GSHS). 2785,63 D.S. 419,51 U/g; Group II (n=4, GSHS at 3 hours). 6053,50 D.S. 2788,84 U/g; Group III (n=4, GSHS at 48 hours). 7424,30 D.S. 997,47 U/g; Group IV (n=10, basal GSSGR). 150,86 D.S. 24,40 mU/mL; Group V (n=7, GSSGR at 3 hours). 212,03 D.S. 53,30 mU/mL; Group VI (n=8, GSSGR at 48 hours). 210,84 D.S. 46,03 mU/mL. CONCLUSIONS: At retinal tissue, BSS Plus(R) intraocular irrigating solution increases GSHS activity without modifications of GSSGR levels. It seems to be related to the < > synthesis of glutathione.

Animals↗

Long-lived polyclonal B-cell lines derived from midgestation mouse embryo lymphohematopoietic progenitors reconstitute adult immunodeficient mice.

Lymphohematopoietic progenitors derived from midgestation mouse embryos were established in long-term cultures with stromal cell monolayers and interleukin 7 (IL-7), giving rise to B-lineage cell lines. The initial emergence and in vitro establishment of these early embryo cell lines were highly sensitive to IL-7-mediated signals, in comparison to cell lines similarly obtained using precursors from late fetal liver (> 13 days postcoitum) and adult bone marrow. The early embryo-derived progenitors spontaneously differentiated in vitro to CD19(+)IgM(+) immature B cells in the presence of optimal concentrations of IL-7, in contrast to those progenitors obtained from late gestation and adult mice, whose differentiation only occurred in the absence of IL-7. The newly in vitro-generated B cells of the early embryo cell lines repopulated adult immunodeficient severe combined immunodeficient mice on their adoptive transfer in vivo and generated specific humoral immune responses after immunization.

2,4-Dinitrophenol↗

Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy.

OBJECTIVES: To assess the incidence and risk factors for hepatotoxicity associated with nevirapine. DESIGN: A prospective cohort study in a teaching and referral hospital involving all consecutive patients who were prescribed a nevirapine-containing antiretroviral regimen between September 1997 and May 2000. METHOD: Cutaneous and hepatic adverse reactions and clinical hepatitis were assessed. Blood analysis including plasma HIV-1 RNA CD4 cell counts, liver chemistry tests, and serology for hepatitis B and C viruses. Hepatotoxicity was defined as an increase of at least threefold in serum alanine aminotransferase or aspartate aminotransferase levels compared with baseline values. RESULTS: Of a total of 610 patients, 82 (13.4%) were antiretroviral naive when commencing nevirapine, and 46.2 and 8.9% were coinfected with hepatitis C and B viruses, respectively. Median duration of exposure to nevirapine was 8.7 months (interquartile range 3.4--14.3). Hepatotoxicity developed in 76 (12.5%), an incidence of 13.1/100 person-years. Kaplan--Meier estimated incidence of hepatotoxicity at 3, 6 and 12 months was 3.7, 9.7 and 20.1%, respectively. In seven (1.1%) patients, hepatotoxicity was associated with clinical hepatitis, which was reversible upon discontinuation of therapy. Multivariate analysis identified the duration of prior exposure to antiretroviral drugs, hepatitis C virus, and higher baseline levels of alanine aminotransferase as independent risk factors for hepatotoxicity. CONCLUSIONS: Hepatotoxicity but not clinical hepatitis was common in HIV-1-infected patients receiving nevirapine-containing regimens and the incidence steadily increased over time. Prolonged exposure to any antiretroviral therapy, coinfection with hepatitis C virus and abnormal baseline levels of alanine aminotransferase identified patients at a higher risk.

Adult↗

New rapid antigen test for diagnosis of pneumococcal meningitis.

Conventional diagnostic methods for bacterial meningitis are frequently not rapid or sensitive enough to guide initial antimicrobial therapy. Streptococcus pneumoniae is the most frequent and severe cause of community-acquired bacterial meningitis and treatment is complicated by the increasing prevalence of antimicrobial resistance to third-generation cephalosporins. We used a new rapid antigen test in the cerebrospinal fluid and urine of patients with suspected bacterial meningitis, and found it to be highly sensitive and specific for the detection of pneumococci. This test might help guide initial therapy for bacterial meningitis according to the local rates of pneumococcal antimicrobial resistance.

Adult↗

Both B and gammadelta TCR(+) lymphocytes regulate alphabeta TCR(+) lymphocytes involved in superantigen specific responses.

Endogenous superantigens (SAg) presented by MHC class II IA molecules induce slow-evolving negative selection of alpha beta T cells. The role of both B and gamma delta T cells on the regulation of these SAg-specific alpha beta T cell responses was addressed in IA(b+)IE(b-) C57BL/6 mice bearing genetically induced B cell and gamma delta T cell deficiencies. B lymphocytes were required in the negative selection of Vbeta5(+)/Vbeta12(+) CD4(+) T cells. In contrast, gamma delta T cells positively stimulated the utilization of the same SAg-responsive alpha beta T cell subsets. These differences started in mature CD4(+) thymocytes and extended to naive T cell pools for B cell negative selection, and up to memory T cells for gamma deltaT cell influences. The levels of SAg-responsive T cells did not vary between C57BL/6 and double deficient (B cell and gamma delta T cell-deficient) congenic mice, implying that both B and gamma delta T cells acted through independent mechanisms.

Animals↗

Streptococcus pneumoniae in community-acquired pneumonia. How important is drug resistance?

Patients hospitalized with community-acquired pneumonia caused by S. pneumoniae strains with intermediate susceptibility to penicillin according to the conventional definition respond well to treatment with adequate doses of beta-lactam antibiotics. All studies currently available comparing mortality between patients with pneumonia caused by nonsusceptible and susceptible pneumococci agree that resistance of MIC 2 mg/L is not associated independently with an increased mortality. Most but not all studies could not prove an effect of microbial resistance on morbidity. There are data suggesting, however, that pneumococcal pneumonia caused by highly resistant strains (MIC > or = 4 mg/L) does affect the outcome. Pneumococcal resistance remains a matter of concern. Most reports show an increase not only of resistance rates, but also of the proportion of highly resistant strains. The selection of initial empirical antimicrobial treatment of patients with community-acquired pneumonia should be performed judiciously. Because the serum and pulmonary levels achieved with penicillin or related drugs are several times higher than the MICs of most strains, pneumonias caused by S. pneumoniae currently defined as not susceptible to penicillin should respond well to treatment with a beta-lactam antibiotic, used in optimal doses. Consequently, there is no reason fundamentally to change the current approach to initial empiric antimicrobial treatment of patients with community-acquired pneumonia. Nevertheless, increases in resistance to macrolides may prompt a limited use of these drugs in the outpatient setting. In any case, treatment failures may occur at higher levels of resistance, and a change in the definition of susceptibility categories toward higher cutoffs for S. pneumoniae seems to be reasonable.

Ambulatory Care↗

[Flavonoid drugs as antioxidant in intraocular irrigating solution].

PURPOSE: To study the protective effect for vitrectomy of intraocular irrigating solutions containing different concentrations of two antioxidants: Meralop and Activadone and compare them with saline solutions and BSS plus. MATERIAL AND METHODS: Seventy-five pigmented rabbits were divided into 8 groups: I. Control (n=8); II. Gas-vitrectomy (n=15); III. Vitrectomy + saline solution (n=6); IV. Vitrectomy + BSS plus (n=9); V. Vitrectomy + Activadone 90 mg/l (n=8); VI. Vitrectomy + Activadone 180 mg/l (n=9); VII. Vitrectomy + Meralop 16 mg/l (n=10); VIII. Vitrectomy + Meralop 64 mg/l (n=10). Antioxidant activity in lens and retina was measured evaluating the levels of lipoperoxides malondyaldehide (MDA) and 4-hydroxynonenal (4-HNE) by spectrophotometry. RESULTS: MDA + 4-HNE concentrations in lens and retina of each group (mean and standard deviation in nmol/g) were: Group I= 3.806DE1.043, 38.787DE10.404. Group II= 4.353DE3.626, 41.554DE18.520. Group III= 297.306DE103.73, 156.69DE6.82. Group IV= 29.39DE15.38, 112.02DE50.12. Group V= 42.31DE20.82, 55.44DE42.21. Group VI= 27.66DE9.29, 181.061DE79.39. Group VII= 134.93DE133.52, 76.89DE36.02. Group VIII= 112.91DE60.30, 79.97DE38.005. CONCLUSIONS: All intraocular irrigation solutions containing antioxidant substances produced lower MDA + 4-HNE levels than saline solution. In the retina, Activadone 90 mg/l produces less MDA concentration than BSS plus.

Animals↗

[Inhibition of lipid peroxidation in retinal tissue during vitrectomy. Effect of intraocular irrigating solution BSS plus].

PURPOSE: Several antioxidant substances have been included in intraocular solutions for vitrectomy in order to reduce oxidative stress. The objective of this work is to evaluate the antioxidant effect of BBS plus(R) (with oxidized glutathione) by means of determining scores of Malondialdehyde (MDA) in retinal tissue at different post vitrectomy time-periods. MATERIAL AND METHODS: Thirty pigmented rabbits distributed in three groups (n=10). Group I: Control (no surgery); group II: Vitrectomy adding BSS plus(R), scoring of malondialdehyde at 3 hours post surgery; group III: Vitrectomy adding BBS plus(R), analysis of malondialdehide at 48 hours after vitrectomy. Retinal samples were used to determine the score of malondialdehyde using ion-pairing high performance liquid chromatography. Statistical analysis was performed using ANOVA-Scheffé test (p<0.05). RESULTS: Scores of free MDA (microgram of retinal tissue) were: group I (n=8): 1.080 S.D. 0.389 microgram group II (n=8): 1.273 S.D. 0.710 microgram and group III (n=10): 0.639 S.D. 0.374 microgram. CONCLUSIONS: BSS plus(R) showed antioxidant effects in retinal tissue which were observed better at a later rather than early stage after a vitrectomy.

Animals↗

Increased phosphoinositide 3-kinase activity induces a lymphoproliferative disorder and contributes to tumor generation in vivo.

Alterations in the cell division:cell death ratio induce multiple autoimmune and transformation processes. Phosphoinositide 3-kinase (PI3K) controls cell division and cell death in vitro, but its effect on the function of the cellular immune system and on tumor formation in mammals is poorly characterized. Here we show that transgenic mice expressing in T lymphocytes an active form of PI3K derived from a thymic lymphoma, p65(PI3K), developed an infiltrating lymphoproliferative disorder and autoimmune renal disease with an increased number of T lymphocytes exhibiting a memory phenotype and reduced apoptosis. This pathology was strikingly similar to that described in mice exhibiting heterozygous loss of the tumor suppressor PTEN, a lipid and protein phosphatase. We show that overexpression of PTEN selectively blocks p65(PI3K)-induced 3T3 fibroblast transformation. Moreover, the early development of T cell lymphomas in p65(PI3K) Tg p53(-/-) mice indicated that PI3K contributes to tumor development. These observations demonstrate that constitutive activation of PI3K extends T cell survival in vivo, affects T cell homeostasis, and contributes to tumor generation, supporting a model in which selective increases in one type of PTEN substrate, the PI3K-derived lipid products, induce tumorigenesis. PI3K thus emerges as a potential target in autoimmune disease and cancer therapy.

Animals↗