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C Miralles

Publications and source records attributed to C Miralles.

At least 19 recordsLinked to original sources
PubMed2006

Long-term monitoring of genotypic and phenotypic resistance to T20 in treated patients infected with HIV-1.

The aim of this study was to investigate the susceptibility to T20 and the dynamics of amino acid changes in HR1 and HR2 of gp41 of HIV-1 obtained from plasma, peripheral blood mononuclear cells (PBMC), and primary isolates (PI) in four highly antiretroviral-experienced patients. These patients received T20 plus an antiretroviral regimen and were followed-up over a period of 40-72 weeks. In one non-responder patient, N43D substitution was detected at 12 weeks of treatment, in association with a value of T20-IC50 of 10 microg/ml (10-fold increase). Double mutations N42T + N43D were observed in plasma RNA at 32 weeks and remained detectable up to 16 weeks after the withdrawal of the drug. The S138A substitution in HR2 was observed in plasma RNA at 32 weeks, and both in plasma RNA and in PI DNA at 40 weeks, associated with an increase of the T20-IC50 to 25 microg/ml (25-fold increase). Mutations V101G and E137K, not reported previously, were also observed in the HR2 region. Whether these new substitutions play a role in T20 resistance needs to be examined. In three temporary responders, coinciding with viral load rebound, G36D, and N42T substitutions were observed at 12, 24, and 40 weeks. G36D mutation was associated with a value of T20-IC50 of 5 microg/ml. The HR2 S138A mutation was detected after the detection of HR1 substitutions and was associated with an increase in the level of T20-IC50 to 125 microg/ml (125-fold increase) All these data reinforce the role of gp41 amino acids 36-45 and the potential influence of the HR2 S138A mutation in the genotypic/phenotypic resistance to T20.

Amino Acid Sequence↗
PubMed2003

Cancer antigen 125 associated with multiple benign and malignant pathologies.

BACKGROUND: Cancer antigen (CA) 125 tumor-associated antigen is a high molecular glycoprotein used for follow-up of epithelial ovarian cancer. The test is often requested as a differential diagnosis in patients with pleural or peritoneal fluid. This study analyzes the prevalence of CA-125 increases in a population of patients attending a general hospital and discusses the possible clinical implications of increased levels. METHODS: On 4 different days, 380 CA-125 assays were performed in randomly selected patients attending our hospital. Serum CA-125 was measured with a commercial enzyme immunoassay, and clinical records were reviewed for assessment of clinical parameters. RESULTS: Sixty-one patients (16%) had increased CA-125. The pathologies of these patients were heart failure in 9 (14.7%), lung disease 11 (18%), hepatic cirrhosis in 7 (11.4%), malignant tumors in 9 (14.7%), intra-abdominal nonhepatic disease in 6 (10%), previous surgery in 17 (27.8%), and miscellaneous in 2 (3%). Effusions were seen in 34 patients (55.7%). CONCLUSIONS: Our data confirm the variety of benign and malignant pathologies coursing with increased CA-125. Cardiovascular and chronic liver disease were the most frequent diagnoses in patients with increased CA-125; this supports the opinion that CA-125 lacks utility as a marker for malignancy. CA-125 could have a role in the follow-up of cardiovascular, hepatic, and tumoral diseases with serosal involvement.

Adolescent↗
PubMed2002

[Systemic inflammation during exacerbations of chronic obstructive pulmonary disease].

OBJECTIVE: The circulating blood levels of several inflammatory cytokines and acute phase proteins are higher in patients with stable chronic obstructive pulmonary disease (COPD). However, whether or not these inflammatory markers increase during COPD exacerbation or are modified by corticosteroid treatment has not been investigated. The objective of this study was therefore 1) to describe changes in several inflammatory markers in systemic circulation during COPD exacerbation, and 2) to assess the potential effects of corticosteroid treatment during exacerbation. METHODS: Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein (CRP) were determined for 10 patients (65 2 years old) with severe COPD (FEV1 35 4% reference) who were hospitalized for acute respiratory failure (PaO2 57 2 mm Hg; PaCO2 48 3 mm Hg). Blood samples were obtained in the emergency room (before starting intravenous corticosteroid treatment), during the first 24 hours of admission, upon discharge and two months later. Eight healthy non-smokers of a similar age (54 3 years) were also studied as control subjects. RESULTS: The COPD patients had higher concentrations of IL-6 (5.1 1.6 vs. 1.8 0.5 pg/mL, p < 0.05) and CRP (2.2 0.4 vs. 0.6 0.2 mg/dL, p < 0.005) than did controls, but the concentrations of IL-8 were similar (29 11.3 vs. 34.7 10.3 pg/mL, p = ns). No statistically significant changes were seen either during recovery, in spite of intravenous corticosteroid treatment, or two months after discharge.The ELISA test used was unable to detect TNF-alpha in any of the samples obtained from either patients or controls. CONCLUSION: The results show that 1) there is evidence of systemic inflammation during exacerbation of COPD, and 2) such systemic inflammation does not appear to be influenced significantly by intravenous corticosteroid treatment.

Adrenal Cortex Hormones↗
PubMed2001

Effect of a novel chemical mixture on senescence processes and plant--fungus interaction in Solanaceae plants.

The effects of exogenous application of a chemical mixture consisting of adipic acid monoethyl ester, furfurylamine, and 1,2,3,4-tetra-O-acetyl-beta-D-glucopyranose (FGA) on various metabolic pathways and the plant-fungus interaction have been studied in Solanaceae plants. Tomato and pepper plants were sprayed with the FGA mixture, and different biochemical parameters such as gas exchange, chlorophyll concentration, protein, cell wall sugar and phenolics contents, and peroxidase and phenylalanine ammonia lyase (PAL) activities were measured. FGA-treated plants showed, in general, an increase in cell wall sugar content and decreases in the chlorophyll degrading rate and the peroxidase activity. These results suggest that FGA (a possible synthetic regulator) could act as a retardant--antisenescence agent in Solanaceae plants. The FGA mixture increased the PAL activity and promoted an overall rise in the concentration of flavonoids and phenolic compounds. Therefore, FGA induced the synthesis of compounds that could give protection to plants against pathogens or insects. To further verify this putative protection, several fungi were inoculated in intact plants. Exogenous FGA applications on intact plants delayed fungus-provoked lesion development. In addition, data also showed that applications of 1,2,3,4-tetra-O-acetyl-beta-D-glucopyranose inhibited fungal growth in vitro. These results confirm that FGA can activate protective mechanisms in plants upon contact with invaders such as fungi.

Adipates↗
PubMed2001

Enhanced neutrophil response in chronic obstructive pulmonary disease.

BACKGROUND: Neutrophils are likely to play a major role in the inflammatory response seen in chronic obstructive pulmonary disease (COPD). This study sought to address the hypothesis that an enhanced neutrophil response to proinflammatory agents in COPD may contribute to their recruitment and activation in the lungs. METHODS: Circulating neutrophils were obtained from 10 patients with COPD, eight long term smokers with normal lung function, and eight healthy never smoking controls. The in vitro production of reactive oxygen species (ROS) was measured by the NADPH oxidase method (respiratory burst) and the surface expression of several adhesion molecules (Mac-1, LFA-1 and L-selectin) was measured by flow cytometry. Measurements were obtained under basal conditions and after stimulation with phorbol myristate acetate (PMA) and tumour necrosis factor alpha (TNFalpha). mRNA levels of p22-phox (a subunit of NADPH oxidase) and Mac-1 (CD11b) were also determined by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Patients with COPD showed enhanced respiratory burst compared with smokers with normal lung function, both under basal conditions (mean (SE) fluorescence intensity (MFI) 15.1 (0.5) v 11.6 (0.5); mean difference -3.4 (95% CI of the difference -5.1 to -1.8), p<0.01) and after PMA stimulation (MFI 210 (7) v 133 (10); mean difference -77 (95% CI of the difference -102 to -52), p<0.01). Mac-1 surface expression was also enhanced in patients with COPD, both under basal conditions (MFI 91 (5) v 45 (3); mean difference -46 (95% CI of the difference -61 to -31), p<0.001) and after stimulation with TNFalpha (MFI 340 (15) v 263 (11); mean difference -77 (95% CI of the difference -119 to -34), p=0.001). These differences were also apparent when patients with COPD were compared with non-smokers (p<0.05). The mRNA levels of p22-phox and Mac-1 (CD11b) were similar in patients with COPD and smokers with normal lung function, suggesting that the observed differences were due to post-transcriptional regulation. CONCLUSIONS: These results demonstrate an enhanced neutrophil response to proinflammatory agents in patients with COPD which may contribute to their enhanced recruitment and activation in the lungs of these patients. These findings support those of other studies which have indicated that the neutrophil is likely to play a major role in the pathogenesis of this disease.

Aged↗
PubMed2001

Prevalence of macroprolactin detected by Elecsys 2010.

BACKGROUND: Macroprolactin or big-big PRL is, usually, a complex of little prolactin (PRL) with anti-PRL autoantibody. There are some patients with hyperprolactinemia showing a high proportion of serum macroprolactin. However, its clinical significance is not clear. Immunoassays used to determine PRL differ in their ability to detect macroprolactin. Moreover, in recent years, PRL assays have changed from isotopic methods (radioimmunoassays and immunoradiometric assays) to non-isotopic automated immunoassays. The effect of macroprolactin on currently used methods is often unknown. The aim of this work was to study the different reactivity of macroprolactin in two immunoassays systems, Elecsys 2010 and ACS Centaur, and to assess the clinical repercussion of this condition. METHODS: We studied retrospectively 956 consecutive routine patients. Samples with a PRL value >636 mIU/l (211 samples) were subjected to the polyethylene glycol (PEG) precipitation test to detect macroprolactin, and 2 of them also to gel filtration chromatography for further confirmation. PRL was measured by Elecsys 2010 and, alternatively, by ACS Centaur. RESULTS: By Elecsys 2010, macroprolactin was detected in 19 patients (9%). After removing macroprolactin, PRL levels were within the normal range in every case but one. When original sera from patients with macroprolactin were processed with ACS Centaur. PRL levels were normal or only marginally elevated. The correlation of PRL values in samples with and without macroprolactin assayed by both systems was 0.64 and 0.98, respectively. CONCLUSIONS: Nearly 9% of hyperprolactinemic patients detected by Elecsys 2010 may have macroprolactin, but the detection rate obtained using ACS Centaur is much lower. As macroprolactin seems to have minimal clinical relevance, it would be important that the users of PRL assays be aware to what extent macroprolactin interferes with their assays, and have available a validated method, such as the PEG precipitation test, to confirm the presence of macroprolactin.

Adolescent↗
PubMed2000

Regulation of iNOS expression and glutathione levels in rat liver by oxygen tension.

Molecular oxygen (O(2)) regulates the expression of a variety of genes. We hypothesized that O(2) tension may regulate iNOS expression in rat liver through the production of reactive oxygen species (ROS) and the reduction of intracellular glutathione (GSH) levels. To investigate this hypothesis, we determined the effects of hyperoxia upon iNOS induction (both at the protein and mRNA level) and the intracellular concentration of GSH in an isolated in vitro perfused rat liver preparation. To study the potential involvement of ROS in the intracellular signaling pathway linking changes in oxygen tension to gene expression, we repeated these determinations in the presence of the thiol antioxidant N-acetyl-L-cysteine (NAC). We found that 95% O(2) tension caused a significant induction of the iNOS protein and mRNA levels paralleled by a significant fall in intracellular GSH concentration. The addition of NAC (1 mM) to the perfusate during hyperoxia blocked the induction of iNOS and restored GSH levels. These results indicate that molecular O(2) regulates the expression of iNOS in rat liver at the transcriptional level, most likely through the production of ROS and the reduction of intracellular GSH levels.

Acetylcysteine↗
PubMed2000

Clinicopathological characteristics of breast carcinomas with allelic loss in the p73 region.

p73, a new member of the p53 family, has been mapped to chromosome 1p 36, a region where loss of heterozygosity (LOH) is frequently observed in primary human tumors. Allelic loss studies involving the 1p arm in breast carcinomas offer rates ranging from 13% to 75%, depending on the genetic interval being studied. We investigated LOH in an intragenic microsatellite marker, and those centromerically flanking the p73 gene, at 1p 36, and their correlations with patient age and 10 pathologic parameters in a series of 193 breast carcinomas. The LOH analysis was performed by amplifying DNA by PCR, using the five markers of the 1p 36 region (p73P1, D1S2694, D1S214, D1S2666 and D1S450). LOH was found in at least one of these markers in 27% of tumors. When we established the comparison between tumors with and without LOH and the distribution of the 10 pathologic parameters considered, we observed statistically significant differences in association with higher histologic grade (p = 0.02), more advanced pathological stage (p = 0.02), peritumoral vessel involvement (p = 0.04) and poorly differentiated carcinomas (p = 0.01), as well as in tumors that concomitantly exhibited lymph node metastases, peritumoral vessel involvement and absence of steroid receptors (p = 0.02). These data suggest that LOH in the p73 region could be pathogenically related to breast cancer and possibly to a poor tumor prognosis.

Adult↗
PubMed2000

Abnormal lipid peroxidation in patients with sleep apnoea.

The prevalence of cardiovascular diseases is increased in patients with the obstructive sleep apnoea syndrome (OSAS). The fall and rise of arterial oxygenation that follows each apnoea may increase lipid peroxidation and contributes to explaining this association. In the present study, the authors determined lipid peroxidation in patients with OSAS and the effect of treatment with continuous positive airway pressure (CPAP). Fourteen male patients with severe OSAS (59+/-5 apnoea x h(-1)) (+/-SEM) and 13 healthy nonsmoking, male volunteers of similar age were studied. Patients were studied at diagnosis and after treatment with CPAP for more than 1 yr (>4 h x night(-1)). A venous blood sample was obtained early in the morning after fasting all night. In patients with OSAS, a sample before and during sleep was also obtained. Low density lipoprotein (LDL) particles were isolated by sequential ultracentrifugation. Their level of oxidation was determined by the thiobarbituric acid assay (TBARs), and their susceptibility to oxidation by the lag phase measurement. Patients with OSAS showed higher TBARs (28.1+/-2.8 versus 20.0+/-1.8 nmol x malondialdehyde x mgLDL protein(-1), p=0.02) and shorter lag phase values (83.8+/-3.4 versus 99.7+/-3.4 min, p=0.005) than controls. These differences were not due to the smoking status of the patient. Likewise, these values did not change significantly throughout the night yet, the lag phase value was significantly improved by treatment with CPAP (124.9+/-8.5 min; p<0.001). These results indicate that obstructive sleep apnoea syndrome is associated with abnormal lipid peroxidation and that this is improved by chronic use of Continuous positive airway pressure. These results can contribute towards explaining the high prevalence of cardiovascular diseases seen in Obstructive sleep apnoea syndrome.

Adult↗
PubMed2000

Changes induced by oxygen in rat liver proteins identified by high-resolution two-dimensional gel electrophoresis.

Molecular oxygen (O2) regulates the expression of a variety of genes. Several of the proteins that respond to changes in oxygen concentration have been identified in a variety of cell lines. We extend these previous studies by analyzing the effect of oxygen on the entire protein expression profile of an intact organ using high-resolution two-dimensional gel electrophoresis. To this end, we used an isolated, in vitro perfused organ preparation to produce two groups of rat livers perfused with high (95% O2, 5% CO2) or low (95% N2, 5% CO2) oxygen concentrations. Using two-dimensional gel electrophoresis we compared the protein expression profiles of both groups of livers. Computer analysis of the files obtained after laser densitometry of the two-dimensional gels revealed two spots that were strongly up-regulated in high PO2 perfused livers compared with low PO2 perfused livers. These spots were analyzed by peptide mass fingerprinting analysis. These spots were identified as arginase 1 (liver-type arginase; EC 3.5.3.1) and mitochondrial enoyl-CoA hydratase 1 (EC 4.2.1.17). The possible role of these proteins in its new context of oxygen availability is discussed.

Animals↗
PubMed1999

Analytical and clinical evaluation of TSH and thyroid hormones by electrochemiluminescent immunoassays.

OBJECTIVES: To perform an analytical evaluation of the new electrochemiluminescent immunoassays (ECLIA) for TSH, FT4, and T3 in the Elecsys 2010 immunoassay system. To assess the clinical classification of patients under suspicion of thyroid disease based on these laboratory assays. MATERIALS AND METHODS: The analytical evaluation included the performance of minimum detectable concentrations, within-assay and inter-assay precision for the three analytes, functional sensitivity and linearity studies for TSH, and method comparison with the previous methods of RIA for FT4 and T3, and IRMA for TSH in current protocols of our institution. 102 patients with clinical suspicion of thyroid disease were assayed by ECLIA and radioactive techniques. Their differential clinical classification based on laboratory tests was studied as well. RESULTS: The minimum detectable concentrations coincided with the manufacturer's: <0.005 mU/L for TSH, <0.30 pmol/L for FT4, and <0.30 nmol/L for T3. Functional sensitivity for TSH was 0.044 mU/L. Over the analytical range tested, within-assay imprecision was below 3.2% for TSH, 2.2% for FT4 and 9.6% for T3, and interassay CVs were below 4.0% for TSH, 5.9% for FT4 and 12.9% for T3. Measurement of diluted sera showed the TSH assay to overestimate recoveries by 18.6%. We have compared sera results of the Elecsys ECLIA assays with those obtained from the IRMA (Spectria-Orion Diagnostica) for TSH: TSH (ECLIA) = 0.074+0.953 TSH (IRMA), (r = 0.974; Sy/x = 2.638), and RIA (Coat a Count-DPC) for FT4:FT4 (ECLIA) = 5.043+0.682 FT4 (RIA), (r = 0.770; Sy/x = 4.774) and RIA (Spectria-Orion Diagnostica) for T3: T3(ECLIA) = -0.461+1.084 T3 (RIA), (r = 0.970; Sy/x = 0.412). When sera from 102 patients were processed by both methods, minimal disagreement in the area of diagnostic classification was observed in 8/102 (7.8%) of the cases. CONCLUSION: The Elecsys 2010 is specially attractive as a routine assay because it is fully automated, obtaining results in only 18 minutes. The analytical assay performance for TSH, FT4 and T3 was shown to be acceptable. Using two different sets of diagnostic tests minimal discrepancies were found in the laboratory assessment for the classification of patients with clinical suspicion of thyroid disease.

Electrochemistry↗
PubMed1999

Frequency of oropharyngeal candidiasis in HIV-infected patients on protease inhibitor therapy.

OBJECTIVE: The purpose of this study was to investigate the effect of HIV-1 protease inhibitors on the frequency of oropharyngeal candidiasis in HIV-infected patients. STUDY DESIGN: A clinical and analytic follow-up was carried out to determine the number of episodes of oropharyngeal candidiasis during HIV-1 protease inhibitor therapy and the relation of this incidence to the CD4 lymphocyte count and circulating neutrophils level. Seventy-five HIV-positive patients were selected, and HIV-1 protease inhibitor therapy was administered to each patient over a minimum of 6 months. These patients did not receive long-term preventive antifungal therapy for oral candidiasis, even as secondary prophylaxis against cryptococcosis. Results were compared with those obtained during the previous 6 months, during which patients had been treated only with reverse transcriptase inhibitors. RESULTS: At least one episode of oropharyngeal candidiasis was seen in 56% (42/75) of patients during reverse transcriptase inhibitor therapy and in only 9.3% (7/75) of patients after the initiation of protease inhibitor therapy. The number of relapses decreased significantly when the 2 follow-up periods were compared (P<.0001). The CD4 and CD8 lymphocyte counts increased significantly with protease inhibitor therapy (P<.001 and P<.05, respectively). During reverse transcriptase inhibitor treatment, the probability of the presentation of oropharyngeal candidiasis correlated with falling CD4 counts (P<.0001). The HIV-1 protease inhibitor therapy was associated with a significant increase in the neutrophil count (P<.01). The probability of the occurrence of some episode of candidiasis correlated inversely with the circulating neutrophil level (P<.05). CONCLUSIONS: Protease inhibitor therapy decreases the frequency of HIV-related oropharyngeal candidiasis. The mechanism involved is unknown, but it can be speculated that a reduction of the viral load increases the number of intact T helper cells, which in turn enhances the number of circulating polymorphonuclear neutrophils and regulates their function by means of colony-stimulating factors.

Adult↗