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Biomedical subjects

S Barroso

Publications and source records attributed to S Barroso.

17 recordsLinked to original sources
PubMed2006

Evolution of suboptimal renal transplantations: experience of a single Spanish center.

The increase in patients on dialysis awaiting transplantation has led to the use of grafts from suboptimal donors. The aim of this study was to analyze the function of suboptimal grafts. The secondary objectives were to study vascular and urological complications, as well as delayed renal function and acute rejection episodes. The study included 135 transplantations performed over 4 years with 27% of grafts being from suboptimal donors. Early graft loss was 12%, of which 69% were due to vascular thrombosis. These thromboses were more frequent among grafts from suboptimal donors (30% vs 4%, P < .001). There were no significant differences between the groups in the incidence of acute rejection episodes (17% vs 13%) or delayed graft function (14% vs 13%). A greater incidence of urologic complications was observed among recipients of grafts from older donors. The 1-year creatinine clearance was significantly lower among recipients of grafts from older donors (73 +/- 19 vs 51 +/- 14 mL/min, P < .0001). Sequential immunosuppressive therapy resulted in a lack of significant differences in creatinine clearance at 6 months, 1 year, or 2 years after transplantation between suboptimal grafts with cold ischemia greater or less than 20 hours or in warm ischemia greater or less than 60 minutes. Logistic regression analysis showed that the best determinant of graft loss was donor age older than 60 years. Accordingly, grafts from suboptimal donors were more likely to be lost during the first month after transplantation, particularly because of thrombosis, which was not due to a higher degree of technical complexity of the transplant operation.

Cadaver↗
PubMed2006

Untoward effects of chronic dual renin-angiotensin system blockade: influence of previous chronic renal failure.

Dual blockade of the renin-angiotensin system (RAS) has increased antiproteinuric effects and so a higher incidence of secondary effects can be expected when this kind of treatment is administered. The aim of this study was to assess the safety of dual blockade of RAS. Seventy-five (54 men and 21 women) patients has been treated in our unit with dual RAS blockade due to proteinuria higher than 1 g/24 h. Mean age was 57.1 +/- 14.0 years. Fifty-three patients had chronic renal failure (CRF) at baseline. Analytical data of 6 months visit and last follow-up visit were recorded. A small reduction of systolic blood pressure and diastolic blood pressure was observed in both treatment groups throughout the study. Neither the CRF patients nor those with normal renal function showed any reduction in mean plasma haemoglobin levels, but differences between groups were significant at the second and third visits (anova). No change was detected in haematocrit. Mean K+ significantly increase at the second visit in the CRF group (from 4.80 +/- 0.64 to 5.23 +/- 0.81 mmol/l, p < 0.001, Student's t-test). There were no changes in normal kidney function group (4.58 +/- 0.37 vs. 4.63 +/- 0.44). At baseline plasmatic creatinine was higher in the CRF group (2.09 +/- 0.60 0.20 mg/dl vs. 0.99 +/- 0.20 mg/dl, p < 0.001, Student's t-test) and creatinine clearance was lower (48.6 +/- 20.7 ml/min vs. 107.0 +/- 0.30 ml/min, p < 0.001, Student's t-test). There was a small increase in creatinine along the follow-up when compared with the normal renal function group (p < 0.001, anova). Conversely, creatinine clearance remain unchanged in the normal renal function group, and there was a decrease in creatinine in CRF patients (p < 0.001). Dual RAS blockade seems to be safe in renal patients even when mild to moderate renal failure is present. Severe hyperkalaemia is uncommon. Small increments in plasmatic creatinine can be seen but they are hardly dangerous. Combined treatment does not significantly influence erythropoiesis.

Analysis of Variance↗
PubMed2006

[Accuracy of indirect estimates of renal function in advanced chronic renal failure patients].

Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formula are indirect estimates of renal function which have been widely accepted, though their accuracies have been scarcely validated in advanced chronic renal failure. The purpose of this study was to determine the accuracy (bias and precision) of these formulas in advanced CRF patients. The study group consisted of 99 unselected patients (62 +/- 15 years, 59 females) with advanced CRF. The glomerular filtration rate (GFR) was measured by Tc(99m) DTPA. Simultaneously, estimates of GFR by CG corrected for 1.73 m2 and MDRD (formula 7) were calculated. Agreement was evaluated graphically, bias was assessed by mean and median difference, and precision by median absolute differences and Bland-Altman plots. Mean GFR by DTPA, CG and MDRD were: 16.24 +/- 4.38 and 16.77 +/- 4.65 and 13.58 +/- 4.27 ml/min/1.73 m2, respectively. MDRD equation significantly underestimated GFR-DTPA (p = 0.0001). Both CG and MDRD correlated significantly with GFR-DTPA (R = 0.53 and R = 0.62, respectively). CG formula performed better than the MDRD equation with respect to bias (0.30 vs -3.24 ml/min/1.73 m2, p = 0.0001), and precision (0.58 vs. -3.11 ml/min/1.73 m2, p = 0.0001). By multiple linear regression, the best determinants of the error of the estimation by CC formula were: serum creatinine (beta = -0.58; p < 0.0001), age (beta = -0.62; p < 0.0001), and body mass index (beta = 0.26, p = 0.004), and by MDRD formula were: serum creatinine (beta = -0.38; p < 0.0001), and body mass index (beta = -0.20, p = 0.03). In conclusion, in unselected patients with advanced chronic renal failure, estimates by CC formula were more accurate than those obtained by MDRD formula. Serum creatinine was the main source of error of the estimation of GFR by both formulas, though demographic and anthropometric characteristics influenced as well on their accuracies.

Disease Progression↗
PubMed2006

[Cystatin C as estimator of glomerular filtration rate in patients with advanced chronic renal disease].

Serum cystatin C (CysC) has been shown to be more accurate than serum creatinine (Cr) in estimating renal function, especially in patients with mildmoderate chronic renal failure. However, it is unknown whether CysC provides or not any advantage over Cr in severe chronic renal failure. The aim of this study was to establish the accuracy of CysC in estimating the glomerular filtration rate (GFR) in advanced chronic renal failure patients. The study group consisted of 94 patients (57 females, mean age 61 +/- 16 years) with advanced chronic renal failure. None of them had thyroid dysfunction or was on corticoid treatment. CFR was measured by TC99mDTPA, and simultaneously, serum CysC (particle enhanced immunonephelometry) and Cr (modified Jaffe's kinetic reaction) were also determined. Serum Cr and CysC levels were correlated with GFR, and the influences of age, sex and diabetes on these correlations were analyzed. The predictive value of CysC and Cr to estimate a GFR less than 15 ml/min/1.73 m2 was analyzed by measuring the crea-under-the-curve (AUC) with Receiver-Operating Characteristics (ROC) plots. The mean CFR was 16.49 +/- 4.65 ml/min/1.73 m2. The mean concentrations of Cr and CysC were 4.19 +/- 1.19 mg/L and 3.44 +/- 0.73 mg/L, respectively. Both Cr and CysC correlated significantly with GFR (R = 0.49, p < 0.0001 and R = 0.52, p < 0.0001, respectively). Age and sex influenced on the correlation between Cr and GFR, but these demographic characteristics did not influence on the correlation between CysC and GFR. The AUC for the prediction of a GFR less than 15 ml/min/1.73 m2 with serum Cr was 0.675 (p = 0.004), while with CysC was 0.633 (p = 0.030). In conclusion, both serum Cr and CysC are highly inaccurate markers of renal function in advanced chronic renal failure patients.

Biomarkers↗
PubMed2005

[Serum uric acid and C-reactive protein levels in patients with chronic kidney disease].

Either inflammation or hyperuricemia has been related with increased cardiovascular risk and mortality. A hypothetical relationship between serum uric acid levels (SUA) and inflammatory markers has never been tested in chronic kidney disease (CKD) patients. The purpose of this study was to determine the prevalence of increased C-reactive protein (CRP) levels in CKD patients, and to test the hypothesis of a relationship between SUA and CRP levels. The study group consisted of 337 patients (174 males, mean age 63 +/- 16 years) with advanced chronic renal failure not yet on dialysis. None of them had overt inflammatory or infectious diseases. High sensitivity CRP levels were analyzed as a binary (above or below median value), or continuous variable (log-transformed CRP), by multiple logistic or linear regression analysis, respectively. Demographics, clinical, and biochemical characteristics, including SUA levels, were the variables tested in these analysis. In a subset of 169 patients without diabetes, the same analysis were carried out, with the inclusion of fasting insulin levels and HOMA-IR as independent variables. Median CRP level was 3.25 mg/L, and mean SUA level was 7.59 +/- 1.94 mg/dl. Patients with CRP levels above the median had significantly higher mean SUA level than that of the rest of study patients (7.93 +/- 1.79 vs 7.24 +/- 2.03 mg/dl, p = 0.001). SUA levels correlated significantly with log-transformed CRP levels (r = 0. 16, p = 0.0022). The relationship between SUA and CRP levels remained statistically significant after adjustment for age, sex, comorbid index, obesity, residual renal function, diuretic and allopurinol treatment, in the multivariate logistic and linear regression models (OR: 1.296, p = 0.0003; and beta: 0.204, p = 0.0002). The significant association between SUA and CRP levels did not change when HOMA-IR and fasting insulin levels were included as independent variables in the subset of 169 patients without diabetes. In conclusion, SUA levels are related with CRP levels in CKD patients.

C-Reactive Protein↗
PubMed2004

[Obesity and mortality in advanced chronic renal failure patients].

A protective effect of obesity on the mortality of end-stage renal failure patients has been observed in several studies. Most of these studies have been based on prevalent dialysis population. The aim of the present study was to evaluate if obesity has beneficial effects on the survival of advanced chronic renal failure patients. The study group consisted of 376 patients (mean age 63 +/- 15 years) with advanced chronic renal failure not yet on dialysis. Obesity was defined as a body mass index (BMI) > or = 30 kg/m2. Grade of comorbidity was quantified by the method devised by Davies. Survival was analyzed as time from the referral to the predialysis outpatient clinic to patient death, censoring from contributing additional survival data to the analysis following transplantation. Kaplan-Meier analysis was used to test survival differences according to quartiles of BMI, and between obese and nonobese patients. Further analysis were performed, stratifying survival curves by comorbid scores, lean body mass, age, and sex. Cox proportional hazard regression models were used to investigate the best determinants of mortality, and the role of obesity adjusted for other covariates. Median survival time was 1,453 days. During the follow-up time, 158 patients (42%) died. Survival differences among quartiles of BMI were statistically significant (Breslow = 10.7, p = 0.017). Patients within the lowest and the highest quartiles of BMI had higher mortality than the rest of patients. Survival curves between obese and non-obese patients did not differ significantly. However, when patients without comorbidity were studied apart, those with obesity showed worse survival than the rest of patients (log-rank = 7.42, p = 0.0064). Since the effect of obesity on mortality did not follow a proportional hazard pattern throughout the study period, multivariable analysis for mortality was stratified by 18 months intervals. The variables which fitted the best model were: age (Hazard Ratio: 1.04), comorbid score (HR: 2.17), serum albumin (HR: 0.62), GFR at the study entry (HR: 0.91), male gender (HR: 1.48), and obesity (HR: 1.51). In conclusion, obesity had no survival benefit in patients with advanced chronic renal failure. Obesity had a noteworthy impact on early mortality of advanced chronic kidney disease patients without comorbidities.

Blood Chemical Analysis↗
PubMed2003

Complement component C7 deficiency in a Spanish family.

Different genetic mutations have been described in complement component C7 deficiency, a molecular defect which is clinically associated with an increased susceptibility to neisserial recurrent infections, although some cases remain asymptomatic. In this work we report the genetic bases of C7 deficiency in one Spanish family. Exon-specific PCR and sequencing revealed a novel point mutation at nucleotide 615 (exon 6) leading to a stop codon (UGG to UGA) in the patient, his mother, and sister. This transversion causes the premature truncation of the C7 protein (W183X). Additionally, we detected a missense mutation at position 1135 (exon 9) located in the first nucleotide of the codon GGG (CGG), resulting in an amino acid change (G357R) in the patient, his father, as well as in his sister. This latter mutation had been previously described in individuals from Moroccan Sephardic Jewish ancestry. Since both heterozygous mutations were found in the patient as well as in his asymptomatic sister, we analyse other meningococcal defence mechanisms such as polymorphisms of the opsonin receptors on polymorphonuclear cells. Results showed that the patient and his sister bore identical combinations of FcgammaRIIA-H/R131 and FcgammaRIIIB-NA1/2 allotypes. Our results provide further evidence that the molecular pathogenesis of C7 deficiency as well as susceptibility to meningococcal disease are heterogeneous, since different families carry different molecular defects, although many of the C7 defects appear to be homogeneous in individuals from certain geographical areas. The missense mutation G357R would make an interesting topic of analysis with regard to meningococcal disease susceptibility in the Spanish population.

Base Sequence↗
PubMed2001

Impaired G protein coupling of the neurotensin receptor 1 by mutations in extracellular loop 3.

The neurotensin receptor 1, NTS1, is a G protein-coupled receptor. We have shown previously that the NTS1 receptor-binding site of the peptide agonist involved residues in extracellular loop 3 and at the extracellular junction of transmembrane domains 4 and 6. Here, we investigated by site-directed mutagenesis residues in extracellular loop 3 that might be involved in agonist-induced activation of the rat NTS1 (rNTS1) receptor. Wild type and mutated receptors were expressed in COS (African green monkey kidney fibroblasts) cells. Labeled agonist and antagonist binding as well as inositol phosphate and cAMP productions were studied. Compared to the wild type NTS1 receptor, the W339A, F344A, H348A and Y349A mutant receptors exhibited (i) decreased proportion of high over low affinity agonist binding sites, (ii) increased sensitivity of high affinity agonist binding to GTP gamma S, and (iii) impaired G protein coupling of high affinity agonist-receptor complexes. The data are consistent with the C-terminal part of extracellular loop 3 being essential for allowing high affinity agonist-NTS1 receptor complexes to couple to G proteins.

Animals↗
PubMed2001

Appropriateness of emergency department visits in a Portuguese university hospital.

STUDY OBJECTIVE: There are no studies in Portugal supporting a common claim that most emergency department visits are inappropriate. The aim of this study was to determine the prevalence of and to evaluate factors associated with an appropriate ED visit in a major public hospital. METHODS: A cross-sectional prospective study was performed at a public university hospital ED. Data for demographic variables, duration of complaint, transfer from other medical sources, and previous medical care for the same complaints were collected by interviewing all patients who arrived at the ED within a consecutive period of at least 24 hours. Data for diagnostic tests, treatment performed, and final patient destination were collected by triage records review. An appropriate ED visit was defined by explicit criteria: interhospital transfer, patient death at the ED, hospitalization, and diagnostic tests or treatments performed. RESULTS: The study included 5,818 adult patients. The prevalence of an appropriate ED visit, by use of our criteria, was 68.7%. Sex was an effect modifier. According to this study, determinants of an appropriate visit for men and women were age 60 years or older and complaints of 24 hours or less and in women but not in men, retired from work and with arrival between midnight and 8 AM. CONCLUSIONS: In a university hospital in Oporto, the majority of ED visits were appropriate according to explicit criteria. Some variables may be associated with appropriateness of ED visits. A duration of the complaint 24 hours or less along with an arrival between midnight and 8 AM in women and age 60 years or older in men were the most important determinants.

Adult↗
PubMed2001

Agonism, inverse agonism, and neutral antagonism at the constitutively active human neurotensin receptor 2.

Two G protein-coupled neurotensin (NT) receptors, termed NTR1 and NTR2, have been identified so far. In contrast to the NTR1, which has been extensively studied, little is known about the pharmacological and biological properties of the NTR2. In the course of characterizing NT analogs that exhibited binding selectivity for the NTR2, we discovered that this receptor constitutively activated inositol phosphate (IP) production. Here, we report on the constitutive activity of the human NTR2 (hNTR2) transfected in COS cells and on compounds that exhibit agonism, inverse agonism, and neutral antagonism at this receptor. IP levels increased linearly with time, whereas they remained constant in mock-transfected cells. Furthermore, IP production was proportional to the amount of hNTR2 present at the cell membrane. SR 48692, a nonpeptide antagonist of the NTR1, stimulated IP production, whereas levocabastine, a nonpeptide histamine H1 antagonist that binds the NTR2 but not the NTR1, behaved as a weak partial inverse agonist. NT analogs modified at position 11 of the NT molecule, in particular by the introduction of bulky aromatic D amino acids, exhibited binding selectivity at the hNTR2 and also behaved as partial inverse agonists, reversing constitutive IP production up to 50%. Finally, NT barely affected constitutive IP production but antagonized the effects of both agonist and inverse agonist compounds, thus behaving as a neutral antagonist. The unique pharmacological profile of the hNTR2 is discussed in the light of its sequence similarity with the NTR1 and the known binding site topology of NT and SR 48692 in the NTR1.

Amino Acid Sequence↗
PubMed2000

Identification of residues involved in neurotensin binding and modeling of the agonist binding site in neurotensin receptor 1.

The neurotensin receptor 1 (NTR1) subtype belongs to the family of G protein-coupled receptors and mediates most of the known effects of the neuropeptide including modulation of central dopaminergic transmission. This suggested that nonpeptide agonist mimetics acting at the NTR1 might be helpful in the treatment of Parkinson's disease and schizophrenia. Here, we attempted to define the molecular interactions between neurotensin-(8-13), the pharmacophore of neurotensin, and the rat NTR1. Mutagenesis of the NTR1 identified residues that interact with neurotensin. Structure-activity studies with neurotensin-(8-13) analogs identified the peptide residues that interact with the mutated amino acids in the receptor. By taking these data into account, computer-assisted modeling techniques were used to build a tridimensional model of the neurotensin-(8-13)-binding site in which the N-terminal tetrapeptide of neurotensin-(8-13) fits in the third extracellular loop and the C-terminal dipeptide binds to residues at the junction between the extracellular and transmembrane domains of the receptor. Interestingly, the agonist binding site lies on top of the previously described NTR1-binding site for the nonpeptide neurotensin antagonist SR 48692. Our data provide a basis for understanding at the molecular level the agonist and antagonist binding modes and may help design nonpeptide agonist mimetics of the NTR1.

Amino Acids↗
PubMed2000

Refractive Error Study in Children: results from La Florida, Chile.

PURPOSE: To assess the prevalence of refractive errors and vision impairment in school-age children in a suburban area (La Florida) of Santiago, Chile. METHODS: Random selection of geographically defined clusters was used to identify a representative sample of children 5 to 15 years of age. Children in the 26 selected clusters were enumerated through a door-to-door survey and invited to report to a community health clinic for examination. Visual acuity measurements, cycloplegic retinoscopy, cycloplegic autorefraction, ocular motility evaluation, and examination of the external eye, anterior segment, media, and fundus were done from April through August 1998. Independent replicate examinations of all children with reduced vision and a sample of those with normal vision were done for quality assurance monitoring in six clusters. RESULTS: A total of 6,998 children from 3,830 households were enumerated, and 5,303 children (75.8%) were examined. The prevalence of uncorrected, presenting, and best visual acuity 0.50 (20/40) or worse in at least one eye was 15.8%, 14.7%, and 7.4%, respectively; 3.3% had best visual acuity 0.50 or worse in both eyes. Refractive error was the cause in 56.3% of the 1,285 eyes with reduced vision, amblyopia in 6.5%, other causes in 4.3%, with unexplained causes in the remaining 32.9%. Myopia -0.50 diopter or less in either eye was present in 3.4% of 5-year-old children, increasing to 19.4% in males and 14.7% in females by age 15. Over this same age range, hyperopia 2.00 diopters or greater decreased from 22.7% to 7.1% in males and from 26.3% to 8.9% in females. Females had a significantly higher risk of hyperopia than males. CONCLUSIONS: Refractive error, associated primarily with myopia, is a major cause of reduced vision in school-age children in La Florida. More than 7% of children could benefit from the provision of proper spectacles. Efforts are needed to make existing programs that provide free spectacles for school children more effective. Further studies are needed to determine whether the upward trend in myopia continues far beyond 15 years of age.

Adolescent↗
PubMed1998

Mutagenesis and modeling of the neurotensin receptor NTR1. Identification of residues that are critical for binding SR 48692, a nonpeptide neurotensin antagonist.

The two neurotensin receptor subtypes known to date, NTR1 and NTR2, belong to the family of G-protein-coupled receptors with seven putative transmembrane domains (TM). SR 48692, a nonpeptide neurotensin antagonist, is selective for the NTR1. In the present study we attempted, through mutagenesis and computer-assisted modeling, to identify residues in the rat NTR1 that are involved in antagonist binding and to provide a tentative molecular model of the SR 48692 binding site. The seven putative TMs of the NTR1 were defined by sequence comparison and alignment of bovine rhodopsin and G-protein-coupled receptors. Thirty-five amino acid residues within or flanking the TMs were mutated to alanine. Additional mutations were performed for basic residues. The wild type and mutant receptors were expressed in COS M6 cells and tested for their ability to bind 125I-NT and [3H]SR 48692. A tridimensional model of the SR 48692 binding site was constructed using frog rhodopsin as a template. SR 48692 was docked into the receptor, taking into account the mutagenesis data for orienting the antagonist. The model shows that the antagonist binding pocket lies near the extracellular side of the transmembrane helices within the first two helical turns. The data identify one residue in TM 4, three in TM 6, and four in TM 7 that are involved in SR 48692 binding. Two of these residues, Arg327 in TM 6 and Tyr351 in TM 7, play a key role in antagonist/receptor interactions. The former appears to form an ionic link with the carboxylic group of SR 48692, as further supported by structure-activity studies using SR 48692 analogs. The data also show that the agonist and antagonist binding sites in the rNTR1 are different and help formulate hypotheses as to the structural basis for the selectivity of SR 48692 toward the NTR1 and NTR2.

Amino Acid Sequence↗
PubMedDate not supplied

[Identification of sentinel lymph node with patent blue V in patients with cutaneous melanoma].

Regional lymphadenectomy in patients with cutaneous malignant melanoma in stages I-U AJC/UICC has not demonstrated improvement either in loco-regional control or in survival. The results of the lymphatic mapping technique have demonstrated that on identifying the sentinel node, the group of patients with microscopic nodal metastases can be selected for regional treatment. We performed the intraoperative lymphatic mapping technique with 1 ml of blue patent V by intradermal injection just around the primary melanoma; after injecting the dye we incised the nodal skin region, identifying the sentinel node by its blue color. The histologic examination, by frozen section of this node, determines whether or not to proceed with a formal lymphadenectomy. We calculated the sensitivity of the dye for the identification of the sentinel node and the Pearson's test was performed between the intraoperative histologic study and the definite pathological result. Thirty one lymphatic mappings were performed in 29 patients with stages I-II malignant cutaneous melanoma. The sentinel node was found in 26/31 explored lymphatic zones, and in 5, it was not found, sensitivity of 84%; 23/26 sentinel nodes were negative and only 3/26 were metastatic in frozen section. The Pearson's test result was 0.78 with a predictive value of 92%. The blue patent V intraoperative lymphatic mapping technique in patients with malignant cutaneous melanoma provided a great sensitivity to identify the sentinel node and allows the identification of patients with high risk of microscopic nodal metastases.

Adult↗