Papers by Wladimiro Jiménez
Clinical Chemistry and Laboratory Medicine (CCLM), 2015
The utility of faecal immunochemical tests (FIT) in assessment of symptomatic patients with lower... more The utility of faecal immunochemical tests (FIT) in assessment of symptomatic patients with lower gastrointestinal symptoms has not been well explored. The aims of this study were to evaluate the diagnostic yield for advanced colorectal neoplasia (ACRN) in symptomatic patients using the first of two FIT samples (FIT/1) and the higher concentration of two FIT samples (FIT/max). Samples from two consecutive bowel motions from 208 symptomatic patients who required colonoscopy were analysed using the HM-JACKarc analyser (Kyowa Medex Co., Ltd., Tokyo, Japan). Patients were categorised into two groups: patients with any ACRN and individuals with other diagnoses or normal colonoscopy. Colonoscopy detected ACRN in 29 patients. In these patients, FIT/1 and FIT/max were significantly higher than in patients with low-risk adenoma (p=0.006 and p=0.024), other findings (p=0.002 and p=0.002) and normal colonoscopy (p<0.001 and p<0.001). The areas under the curves (AUC) of FIT/1 and FIT/max were 0.71 and 0.69, respectively. Undetectable FIT/1 rules out 96.6% of ACRN and the specificity was 10.6%. Increasing the FIT/1 cut-off to 10 μg Hb/g faeces, sensitivity and specificity were 34.5% and 87.2%, respectively. Similar results were obtained using FIT/max with 20 μg Hb/g faeces cut-off, providing a sensitivity and specificity of 34.5% and 85.6%, respectively. Undetectable FIT is a good strategy to rule-out ACRN in symptomatic patients. The diagnostic yield of collecting two samples for FIT can be achieved with one sample, but a lower faecal haemoglobin concentrations (f-Hb) cut-off is required.
Seminars in Liver Disease, 1994
... 1994 Feb;14(1):44-58. Antidiuretic hormone and the pathogenesis of water retention in cirrhos... more ... 1994 Feb;14(1):44-58. Antidiuretic hormone and the pathogenesis of water retention in cirrhosis with ascites. ... MeSH Terms. Animals; Ascites/metabolism*; Body Water/metabolism*; Humans; Kidney/metabolism; Liver Cirrhosis/drug therapy; Liver Cirrhosis/metabolism*; ...
Previous studies have shown that severe ovarian hyperstimulation syndrome (OHSS) is secondary to ... more Previous studies have shown that severe ovarian hyperstimulation syndrome (OHSS) is secondary to circulatory dysfunction due to the simultaneous occurrence of increased vascular permeability and marked arteriolar vasodilation which lead to an intense homeostatic stimulation of the renin-aldosterone and sympathetic nervous systems and antidiuretic hormone (ADH). In the present report, we have investigated the correlation between changes in haematocrit concentration, and white blood cell (WBC) and platelet counts and the severity of OHSS, as assessed by these markers of effective intra-arterial blood volume, in a series of 50 patients. In comparison with recovery values (4-5 weeks after hospital discharge), OHSS patients showed arterial hypotension, tachycardia, oliguria, very high plasma concentrations of renin, aldosterone, norepinephrine and ADH, and increased mean haematocrit values and WBC and platelet counts. The haematocrit concentration values were directly related to the plasma concentrations of vasoactive substances (plasma renin activity, aldosterone, norepinephrine and ADH) during OHSS (P Ͻ 0.001). In contrast, no correlation was evident between WBC or platelet counts and neurohormonal measurements during the syndrome. It is concluded that haematocrit, but not WBC or platelet counts, can act as a biological marker of the severity of OHSS as indicated by plasma measurement of volume-dependent endogenous vasoactive substances.
PloS one, 2015
Biomarkers are potentially useful in assessment of outcomes in patients with cirrhosis, but infor... more Biomarkers are potentially useful in assessment of outcomes in patients with cirrhosis, but information is very limited. Given the large number of biomarkers, adequate choice of which biomarker(s) to investigate first is important. Analysis of potential usefulness of a panel of urinary biomarkers in outcome assessment in cirrhosis. Fifty-five patients with acute decompensation of cirrhosis were studied: 39 had Acute Kidney Injury (AKI) (Prerenal 12, type-1 HRS (hepatorenal syndrome) 15 and Acute Tubular Necrosis (ATN) 12) and 16 acute decompensation without AKI. Thirty-four patients had Acute-on-chronic liver failure (ACLF). A panel of 12 urinary biomarkers was assessed, using a multiplex assay, for their relationship with ATN, ACLF and mortality. Biomarker with best accuracy for ATN diagnosis was NGAL (neutrophil-gelatinase associated lipocalin): 36 [26-125], 104 [58-208] and 1807 [494-3,716] μg/g creatinine in Prerenal-AKI, type-1 HRS and ATN, respectively; p<0.0001 (AUROC 0.95...
Vasopressin analogues associated with albumin improve renal function in hepatorenal syndrome (HRS... more Vasopressin analogues associated with albumin improve renal function in hepatorenal syndrome (HRS). The current study was aimed at assessing the efficacy of the treatment, predictive factors of response, recurrence of HRS, and survival after therapy. Twenty-one consecutive patients with HRS (16 with type 1 HRS, 5 with type 2 HRS) received terlipressin (0.5-2 mg/4 hours intravenously) until complete response was achieved (serum creatinine level < 1.5 mg/dL) or for 15 days; 13 patients received intravenous albumin together with terlipressin. Twelve of the 21 patients (57%) showed complete response. Albumin administration was the only predictive factor of complete response (77% in patients receiving terlipressin and albumin vs. 25% in those receiving terlipressin alone, P ؍ .03). Treatment with terlipressin and albumin was associated with a remarkable decrease in serum creatinine level, increase in arterial pressure, and suppression of the renin-aldosterone system. By contrast, no significant changes in these parameters were found in patients treated with terlipressin alone. Only 1 patient showed ischemic adverse effects. Recurrence of HRS occurred in 17% of patients with complete response. The occurrence of complete response was associated with an improved survival. In conclusion, terlipressin therapy reverses HRS in a high proportion of patients. Recurrence rate after treatment withdrawal is uncommon. Albumin appears to improve markedly the beneficial effects of terlipressin. (HEPATOLOGY 2002;36:941-948.) Abbreviation: HRS, hepatorenal syndrome. From the
1 The maintenance of renal function in decompensated cirrhosis is highly dependent on prostagland... more 1 The maintenance of renal function in decompensated cirrhosis is highly dependent on prostaglandins (PGs). Since PG synthesis is mediated by cyclooxygenase-1 and -2 (COX-1 and COX-2), the present study was designed to examine which COX isoform is involved in this phenomenon.
PLoS ONE, 2014
Early detection of fibrosis progression is of major relevance for the diagnosis and management of... more Early detection of fibrosis progression is of major relevance for the diagnosis and management of patients with liver disease. This study was designed to find non-invasive biomarkers for fibrosis in a clinical context where this process occurs rapidly, HCV-positive patients who underwent liver transplantation (LT). We analyzed 93 LT patients with HCV recurrence, 41 non-LT patients with liver disease showing a fibrosis stage F$1 and 9 patients without HCV recurrence who received antiviral treatment before LT, as control group. Blood obtained from 16 healthy subjects was also analyzed. Serum samples were fractionated by ion exchange chromatography and their proteomic profile was analyzed by SELDI-TOF-MS. Characterization of the peptide of interest was performed by ion chromatography and electrophoresis, followed by tandem mass spectrometry identification. Marked differences were observed between the serum proteome profile of LT patients with early fibrosis recurrence and non-recurrent LT patients. A robust peak intensity located at 5905 m/z was the distinguishing feature of non-recurrent LT patients. However, the same peak was barely detected in recurrent LT patients. Similar results were found when comparing samples of healthy subjects with those of non-LT fibrotic patients, indicating that our findings were not related to either LT or HCV infection. Using tandem mass-spectrometry, we identified the protein peak as a Cterminal fragment of the fibrinogen a chain. Cell culture experiments demonstrated that TGF-b reduces a-fibrinogen mRNA expression and 5905 m/z peak intensity in HepG2 cells, suggesting that TGF-b activity regulates the circulating levels of this protein fragment. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen a chain as an early serum biomarker of fibrogenic processes in patients with liver disease.
Journal of Hepatology, 2002
Reproductive BioMedicine Online, 2009
Steroids, 2015
The existence of urinary testosterone (T) metabolites conjugated with cysteine has been recently ... more The existence of urinary testosterone (T) metabolites conjugated with cysteine has been recently reported. The formation of a ring double bond by a phase I metabolic transformation and the subsequent nucleophilic conjugation with glutathione was proposed as a putative metabolic pathway for the occurrence of these metabolites in urine. The main goal of the present study was to confirm the first step of the postulated pathway. For that purpose, human hepatocyte cells systems were incubated with a pure T standard. The cell culture supernatants were analyzed by liquid chromatography coupled to mass spectrometry using a selected reaction monitoring method. Major T metabolites such as androsterone and 4-androstene-3,17-dione, together with the recently reported Δ(1) and Δ(6) metabolites were simultaneously quantified. The formation of 1,4-androstadien-3,17-dione, 4,6-androstadien-3,17-dione, 17β-hydroxy-4,6-androstadien-3-one and 17β-hydroxy-1,4-androstadien-3-one (boldenone) after incubation of T in hepatocyte cell cultures was demonstrated by comparing the retention times and the ion ratios of the metabolites with those obtained by analysis of commercial standards. Thus, the formation of double bonds Δ(1) and Δ(6) by hepatic phase I metabolism of T was confirmed. Analogously to T, this pathway might also be present in other steroids, opening the possibility of targeting additional biomarkers.
Clinical Gastroenterology, 2005
The cardiovascular system mainly develops during embryogenesis and only to a limited extent in po... more The cardiovascular system mainly develops during embryogenesis and only to a limited extent in postnatal life. This is a complex process that involves proliferation, migration, and differentiation of endothelial cells and, in a final step, recruitment of smooth muscle cells to form mature vessels. These are key events in the formation of new vessels that are spatially and temporally orchestrated
Chronic Liver Failure, 2010
Page 1. Angiogenesis and Vascular Growth in Liver Diseases Manuel Morales-Ruiz, Sònia Tugues, and... more Page 1. Angiogenesis and Vascular Growth in Liver Diseases Manuel Morales-Ruiz, Sònia Tugues, and Wladimiro Jiménez CONTENTS INTRODUCTION LONG-TERM STRUCTURAL CHANGES OF THE HEPATIC ANGIOARCHI ...
Kidney International, 1991
Doses of endothelin have natriuretic effects in conscious rats with cirrhosis and ascites. MAP, R... more Doses of endothelin have natriuretic effects in conscious rats with cirrhosis and ascites. MAP, RPF, GFR, V and UNaV were measured in nine conscious control and in 11 conscious cirrhotic rats with ascites before and following two bolus injections (100 and 600 pmol/kg body wt) of endothelin (ET). PRA and plasma concentration of aldosterone and ANP were measured in basal
Clinica chimica acta; international journal of clinical chemistry, Jan 25, 2014
Prostate health index (phi), a measure calculated as p2PSA/fPSA × √tPSA, has shown valuable resul... more Prostate health index (phi), a measure calculated as p2PSA/fPSA × √tPSA, has shown valuable results in the detection of prostate cancer (PCa), improving the prediction of the aggressiveness of the tumor. The aim of our study was to test whether prostate volume influences phi performance using univariate and multivariate models. 220 patients with PSA<10 μg/L (102 with negative biopsy and 118 with PCa) were included in the study. Serum concentrations of tPSA, fPSA and p2PSA were measured on Access2 analyzer. The higher accuracy was found for phi, obtaining an AUC of 0.748. Bigger AUCs were obtained for phi, %p2PSA, %fPSA and tPSA in patients with small prostate volume (≤35 cc); meanwhile, the lowest AUCs were found in patients with large prostate volume (>50 cc). Including phi and %p2PSA in a multivariable analysis based on patient age, prostate volume, tPSA, and %fPSA accuracy increased from 0.762 to 0.802 (logistic regression model) or 0.815 (artificial neural network). Accura...
Journal of Hepatology, 2005
Background/Aims: Ascites in patients with cirrhosis is associated with worsening of systemic hemo... more Background/Aims: Ascites in patients with cirrhosis is associated with worsening of systemic hemodynamics. Thus, the aim of this study was to investigate the biological activity of ascites on endothelial cells.
Gastroenterology, 2014
The latest generation of fecal immunochemical tests (FIT) allows for quantitation of hemoglobin i... more The latest generation of fecal immunochemical tests (FIT) allows for quantitation of hemoglobin in feces, allowing for selection of optimal cut-off concentrations. We investigated whether individuals with positive results from quantitative FITs, in combination with other factors, could be identified as being at greatest risk for advanced colorectal neoplasia. METHODS: In a retrospective study, we analyzed data from a consecutive series of 3109 participants with positive results from FITs (20 mg/g of feces) included in the first round of the Barcelona colorectal cancer screening program, from December 2009 through February 2012. All participants underwent colonoscopy and were assigned to groups with any advanced colorectal neoplasia or with nonadvanced colorectal neoplasia (but with another diagnosis or normal examination findings). RESULTS: Median fecal hemoglobin concentrations were significantly higher in participants with advanced colorectal neoplasia (105 mg/g; interquartile range, 38-288 mg/g) compared with participants with nonadvanced colorectal neoplasia (47 mg/g; interquartile range, 23-119 mg/g) (P < .001). Positive predictive values for advanced colorectal neoplasia, determined using arbitrary fecal hemoglobin concentrations, differed with sex and age. Multivariate logistic regression analysis identified sex (men: odds ratio [OR], 2.07; 95% confidence interval, 1.78-2.41), age (60-69 y: OR, 1.24; 95% confidence interval, 1.07-1.44), and fecal hemoglobin concentration (>177 mg/g: OR, 3.80; 95% confidence interval, 3.07-4.71) as independent predictive factors for advanced colorectal neoplasia. Combining these factors, we identified 16 risk categories associated with different probabilities of identifying advanced colorectal neoplasia. Risk for advanced colorectal neoplasia increased 11.46-fold among individuals in the highest category compared with the lowest category; positive predictive values ranged from 21.3% to 75.6%. CONCLUSIONS: Fecal hemoglobin concentration, in addition to sex and age, in individuals with positive results from FITs can be used to stratify probability for the detection of advanced colorectal neoplasia. These factors should be used to prioritize individuals for colonoscopy examination.
Nephron, 1984
8 cirrhotics with hyponatremia were given demeclocycline (DMC) 900 mg/day to investigate its effe... more 8 cirrhotics with hyponatremia were given demeclocycline (DMC) 900 mg/day to investigate its effect on renal function, plasma renin activity, aldosterone and urinary excretion of prostaglandin E2 and kallikrein. In 7 patients DMC induced an increase of free water clearance (from -0.36 +/- 0.06 to 0.13 +/- 0.06 ml/min) and serum sodium concentration (from 125.4 +/- 0.09 to 131.1 +/- 1.0 mEq/l, mmol/l). In 5 of these patients DMC also induced a marked reduction of glomerular filtration rate (from 72.2 +/- 6.2 to 31,2 +/- 4.7 ml/min) and renal plasma flow (from 468 +/- 98 to 195 +/- 55 ml/min) which could not be explained on the basis of hypovolemia. In each case this renal impairment was not associated with changes in urinary concentration of beta 2-microglobulin, urinary casts excretion, fresh urine sediment or urine protein content and disappeared after discontinuation of the drug. DMC induced a marked increase in the urinary excretion of prostaglandin E2 (from 0.82 +/- 0.27 to 6.16 +/- 1.91 ng/min) in 6 out of the 7 patients who responded to DMC and a marked reduction in urinary kallikrein (from 16.1 +/- 4.4 to 4.2 +/- 1.6 pkat/min) in the 5 patients who developed renal insufficiency. The serum DMC concentration was greater than 5 micrograms/ml in all patients who responded to DMC, greater than 8 micrograms/ml in all cases who developed renal insufficiency and of 3 micrograms/ml in the case not responding to DMC. (ABSTRACT TRUNCATED AT 250 WORDS)
The Journal of Molecular Diagnostics, 2010
Quantitative fluorescent PCR (QF-PCR) has been used by many laboratories for prenatal diagnosis o... more Quantitative fluorescent PCR (QF-PCR) has been used by many laboratories for prenatal diagnosis of the most common aneuploidies. QF-PCR is rapid , costeffective , and suitable for automation and can detect most abnormalities diagnosed by conventional karyotyping. Whether QF-PCR should be used alone in most of the samples and in which karyotyping should also be offered is currently a topic of debate. We evaluated and compared the results obtained from 7679 prenatal samples in which conventional karyotype and QF-PCR had been performed , including 1243 chorionic villi and 6436 amniotic fluid samples. Concordant QF-PCR and karyotype results were obtained in 98.75% of the samples. An abnormal karyotype associated with adverse clinical outcome undetected by QF-PCR was found in 0.05% of samples. Therefore, QF-PCR can be used alone in a large number of samples studied in a prenatal laboratory , thereby reducing both the workload in cytogenetic laboratories and parental anxiety when awaiting results. (J Mol Diagn 2010, 12:828 -834;
European Journal of Biochemistry, 1999
Activated mesangial cells may play an important part in glomerulonephritis. Cytokines can modulat... more Activated mesangial cells may play an important part in glomerulonephritis. Cytokines can modulate the release of prostanoids by human mesangial cells (HMC). We have investigated the effects of pro-inflammatory stimuli on COX-2 expression in HMC and its potential modulation by interleukin (IL)-13. HMC released increased amounts of prostaglandin E 2 (PGE 2 ) after treatment with several combinations of IL-1b, tumor necrosis factor (TNF)-a and/or lipopolysaccharide. Increases in PGE 2 correlated with the induction of COX-2 protein expression. The accumulation of PGE 2 elicited by a combination of IL-1b/TNF-a correlated closely with the temporal pattern of COX-2 protein expression, which reflected the induction of COX-2 mRNA. IL-13 inhibited IL-1b/TNF-a-elicited PGE 2 production, as well as COX-2 protein and mRNA expression in a concentration-dependent fashion. With 50 ng´mL ±1 IL-13 these parameters were inhibited by 90, 80 and 84%, respectively. In HMC transfected with the 5 H regulatory region of the COX-2 gene, IL-13 suppressed cytokine-induced promoter activation. Our results suggest that COX-2 expression is a major target for IL-13-mediated abrogation of prostaglandin release by HMC and support that this process takes place by transcriptional inhibition of the COX-2 gene.
The FASEB Journal, 2003
The existence of an increased number of Kupffer cells is recognized as critical in the initiation... more The existence of an increased number of Kupffer cells is recognized as critical in the initiation of the inflammatory cascade leading to liver fibrosis. Because 5-lipoxygenase (5-LO) is a key regulator of cell growth and survival, in the current investigation we assessed whether inhibition of the 5-LO pathway would reduce the excessive number of Kupffer cells and attenuate inflammation and fibrosis in experimental liver disease. Kupffer cells were the only liver cell type endowed with a metabolically active 5-LO pathway (i.e., expressed mRNAs for 5-LO, 5-LO-activating protein [FLAP], and leukotriene [LT] C 4 synthase and generated LTB 4 and cysteinyl-LTs). Both the selective 5-LO inhibitor AA861 and the FLAP inhibitor BAY-X-1005 markedly reduced the number of Kupffer cells in culture. The antiproliferative properties of AA861 and BAY-X-1005 were associated with the occurrence of condensed nuclei, fragmented DNA, and changes in DNA content and cell cycle frequency distribution consistent with an apoptotic process. In vivo, in carbon tetrachloride-treated rats, BAY-X-1005 had a significant antifibrotic effect and reduced liver damage and the hepatic content of hydroxyproline. Together, these findings indicate a novel mechanism by which inactivation of the 5-LO pathway could disrupt the sequence of events leading to liver inflammation and fibrosis.
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Papers by Wladimiro Jiménez