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Biomedical subjects

S Escolano

Publications and source records attributed to S Escolano.

18 recordsLinked to original sources

Smooth pursuit eye movements are associated with phonological awareness in preschool children.

Phonological awareness is strongly related to reading ability, but reports are more conflicting concerning the association of high level oculomotor skills with reading. Here, we show that phonological awareness is specifically associated with the ability to perform smooth pursuit eye movements in preschool children. Two large independent samples of preschool children (n=838 and n=732) aged 5-6.4 years, without history of neurological disorder, were examined by school medical doctors for visual and oculomotor problems. Nineteen percent of the children in the first sample and 14% in the second failed at the clinical evaluation of smooth pursuit eye movements, and 17 and 15%, respectively, presented another visual or oculomotor problem. Ten short cognitive tests were performed by the same children. Visual and oculomotor problems other than a failure on smooth pursuit were not consistently related to the cognitive tasks, with one exception, the visual recognition of letters. Children who failed at smooth pursuit obtained lower scores at a number of cognitive tasks, and especially phonological awareness tasks and copy of visually presented trajectories. Poor working memory and/or failure of anticipation during the tracking of a visual or auditory stimulus related to frontal cortex immaturity may explain these associations in preschool children.

Awareness↗

A new algorithm for haplotype-based association analysis: the Stochastic-EM algorithm.

It is now widely accepted that haplotypic information can be of great interest for investigating the role of a candidate gene in the etiology of complex diseases. In the absence of family data, haplotypes cannot be deduced from genotypes, except for individuals who are homozygous at all loci or heterozygous at only one site. Statistical methodologies are therefore required for inferring haplotypes from genotypic data and testing their association with a phenotype of interest. Two maximum likelihood algorithms are often used in the context of haplotype-based association studies, the Newton-Raphson (NR) and the Expectation-Maximisation (EM) algorithms. In order to circumvent the limitations of both algorithms, including convergence to local minima and saddle points, we here described how a stochastic version of the EM algorithm, referred to as SEM, could be used for testing haplotype-phenotype association. Statistical properties of the SEM algorithm were investigated through a simulation study for a large range of practical situations, including small/large samples and rare/frequent haplotypes, and results were compared to those obtained by use of the standard NR algorithm. Our simulation study indicated that the SEM algorithm provides results similar to those of the NR algorithm, making the SEM algorithm of great interest for haplotype-based association analysis, especially when the number of polymorphisms is quite large.

Algorithms↗

SELPLG gene polymorphisms in relation to plasma SELPLG levels and coronary artery disease.

P-selectin and P-selectin glycoprotein ligand (SELPLG, selectin P ligand) constitute a receptor/ligand complex that is likely to be involved in the development of atherosclerosis and its complications. While the genetic variability of P-selectin has already been investigated in depth, that of the SELPLG gene has not yet been extensively explored. The coding and regulatory sequences of the SELPLG were screened and nine polymorphisms were identified. The identified polymorphisms were genotyped in the AtheroGene study, a case-control study of coronary artery disease (CAD). Haplotype analysis revealed that two polymorphisms of SELPLG, the M62I and the VNTR, independently influenced plasma SELPLG levels. Conversely, haplotypes of SELPLG were not associated with CAD risk.

Adult↗

Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II Trial.

BACKGROUND: beta-Blockade-induced benefit in heart failure (HF) could be related to baseline heart rate and treatment-induced heart rate reduction, but no such relationships have been demonstrated. METHODS AND RESULTS: In CIBIS II, we studied the relationships between baseline heart rate (BHR), heart rate changes at 2 months (HRC), nature of cardiac rhythm (sinus rhythm or atrial fibrillation), and outcomes (mortality and hospitalization for HF). Multivariate analysis of CIBIS II showed that in addition to beta-blocker treatment, BHR and HRC were both significantly related to survival and hospitalization for worsening HF, the lowest BHR and the greatest HRC being associated with best survival and reduction of hospital admissions. No interaction between the 3 variables was observed, meaning that on one hand, HRC-related improvement in survival was similar at all levels of BHR, and on the other hand, bisoprolol-induced benefit over placebo for survival was observed to a similar extent at any level of both BHR and HRC. Bisoprolol reduced mortality in patients with sinus rhythm (relative risk 0.58, P:<0.001) but not in patients with atrial fibrillation (relative risk 1.16, P:=NS). A similar result was observed for cardiovascular mortality and hospitalization for HF worsening. CONCLUSIONS: BHR and HRC are significantly related to prognosis in heart failure. beta-Blockade with bisoprolol further improves survival at any level of BHR and HRC and to a similar extent. The benefit of bisoprolol is questionable, however, in patients with atrial fibrillation.

Adrenergic beta-Antagonists↗

A multi-state model for evolution of intensive care unit patients: prediction of nosocomial infections and deaths.

Nosocomial (hospital-acquired) infections are very frequent in intensive care units (ICU). The risk of death after severe infection is high, but the precise rate of death in ICU attributable to nosocomial infection is not known. The goal of this project was to build a statistical model to predict the occurrence of nosocomial infections in ICU and the outcome of the patients. We collected data on 676 consecutive patients admitted to an ICU for more than 24 hours between 1993 and 1996. The following data were collected for each patient: history; clinical examination at entry; subsequent infections; outcome. A multi-state heterogeneous semi-Markov model was determined and then validated; the initial data set was randomly split into two groups: two-thirds (450 patients) to build the model and one-third (226 patients) to validate it. The model defined five states: ICU admission; first simple infection; first complicated infection; death, and discharge from the ICU. Transitions between these states determined nine different events. The global model of patient histories can be divided into nine survival models, each corresponding to one of these events. The possible events from a given state were considered to be competing. Since many risk factors induced non-proportional hazard functions, piecewise exponential models were used to model event occurrence. The effect of continuous covariates on hazard functions has been described with a non-parametric method that enables non-linear relations to be shown. Among other things, the model allows patients' post-admission histories to be predicted from data available at ICU admission. The bootstrap estimator of the attributable risk of death due to simple or complicated nosocomial infections is 44.2 percent (95 percent CI 26.0-61.6 percent). We were also able to characterize the most highly exposed patients, those who comprise the high-risk group on whom prevention efforts must be focused.

Cross Infection↗

Antibiotic susceptibility pattern of Mycobacterium marinum.

In vitro activities of 17 antibiotics against 53 clinical strains of Mycobacterium marinum, an atypical mycobacterium responsible for cutaneous infections, were determined using the reference agar dilution method. Rifampin and rifabutin were the most active drugs (MICs at which 90% of the isolates tested were inhibited [MIC(90)s], 0.5 and 0.6 microgram/ml, respectively). MICs of minocycline (MIC(90), 4 microgram/ml), doxycycline (MIC(90), 16 microgram/ml), clarithromycin (MIC(90), 4 microgram/ml), sparfloxacin (MIC(90), 2 microgram/ml), moxifloxacin (MIC(90), 1 microgram/ml), imipenem (MIC(90), 8 microgram/ml), sulfamethoxazole (MIC(90), 8 microgram/ml) and amikacin (MIC(90), 4 microgram/ml) were close to the susceptibility breakpoints. MICs of isoniazid, ethambutol, trimethoprim, azithromycin, ciprofloxacin, ofloxacin, and levofloxacin were above the concentrations usually obtained in vivo. For each drug, the MIC(50), geometric mean MIC, and modal MIC were very close, showing that all the strains had a similar susceptibility pattern. Percent agreement (within +/-1 log(2) dilution) between MICs yielded by the Etest method and by the agar dilution method used as reference were 83, 59, 43, and 24% for minocycline, rifampin, clarithromycin, and sparfloxacin, respectively. Reproducibility with the Etest was low, in contrast to that with the agar dilution method. In conclusion, M. marinum is a naturally multidrug-resistant species for which the agar dilution method is more accurate than the Etest for antibiotic susceptibility testing.

Anti-Bacterial Agents↗

Outcome of Budd-Chiari syndrome: a multivariate analysis of factors related to survival including surgical portosystemic shunting.

The aim of this study was to assess the factors, including surgical portosystemic shunts, which affect survival in adults with Budd-Chiari syndrome. Multivariate retrospective analysis was performed using characteristics recorded at the time of diagnosis in 120 patients admitted from 1970 to 1992, of whom 82 were treated with surgical portosystemic shunts and 38 received only medical therapy. The 1-, 5-, and 10-year survival rates were 77 +/- 4%, 64 +/- 5%, and 57 +/- 6%, respectively. Survival was significantly better in the subgroup of patients diagnosed after versus before 1985. In both subgroups, and in patients with, as well as in patients without surgical shunts, 4 factors were found to be inversely and independently related to survival: age, response of ascites to diuretics, Pugh score, and serum creatinine. In patients diagnosed since 1985, an index combining these 4 factors allowed to differentiate patients with a good outcome (5-year survival 95%) from those with a poor outcome (5-year survival 62%; P <.05). There was no statistically significant and independent influence of surgical portosystemic shunts on survival. In conclusion, age, severity of liver failure, and presence of refractory ascites are the main prognostic factors in Budd-Chiari syndrome. Increased survival in recent years is consistent with improved management of hypercoagulable states as well as improved general care. It is uncertain whether surgical portosystemic shunting favorably modifies survival. Therefore, we recommend that surgical shunting should be restricted to management of refractory ascites or variceal bleeding in patients with otherwise good prognostic factors.

Adolescent↗

Prognostic value of bisoprolol-induced hemodynamic effects in heart failure during the Cardiac Insufficiency BIsoprolol Study (CIBIS).

BACKGROUND: To further evaluate the mechanism of beta-blocker-induced benefits in heart failure, the relationships between bisoprolol-induced hemodynamic effects and survival were studied during the Cardiac Insufficiency BIsoprolol Study (CIBIS). METHODS AND RESULTS: In 557 patients studied, bisoprolol significantly reduced heart rate (-16.3+/-15.3 versus -1.6+/-13.4 bpm, respectively; P<.001) compared with placebo at 2 months after inclusion in the study. Heart rate change over time had the highest predictive value for survival (P<.01). Left ventricular fractional shortening (LVFS) significantly increased in the bisoprolol group compared with the placebo group 5 months after inclusion (+0.04+/-0.06 versus -0.001+/-0.05, respectively; P<.001; n=160). LVFS change over time was also significantly correlated with further survival (P<.02 by Cox analysis). Using a nonparametric approach, we demonstrated a significant interaction between study treatment group and LVFS over time. Patients who demonstrated improvement of LVFS over time (82% and 51% of patients in the bisoprolol and the placebo groups, respectively; P<.02) were at lower risk, but the hazard did not further decrease with a further increase of fractional shortening, and there was no significant difference between study treatment groups. Finally, it could be demonstrated that each of the three factors (heart rate change over time, LVFS change over time, and bisoprolol treatment) made a specific contribution to mortality rate. CONCLUSIONS: Preservation of left ventricular function appears to play a key role in the bisoprolol-induced beneficial effects on prognosis in heart failure. Short-term beta-blocker-induced cardiac effects could provide a means to identify those patients who will experience improved survival over the long term.

Adrenergic beta-Antagonists↗

Prognostic value of plasma endothelin-1 in patients with chronic heart failure.

AIMS: Endothelin-1 is a potent vasoconstrictive and multifunctional peptide. Elevated concentrations have been reported in congestive heart failure. We hypothesized that the level of endothelin-1 in plasma is a prognostic marker in congestive heart failure. METHODS AND RESULTS: Plasma levels of endothelin-1 were measured by radioimmunoassay in 120 congestive heart failure patients with ischaemic or non-ischaemic cardiomyopathy (mean ejection fraction 28 +/- 11%, in New York Heart Association (NYHA) functional class I:21, class II 35, class III: 61, class IV: 3). During a median follow-up of 361 +/- 338 days, 14 cardiac deaths occurred. In the univariate Cox model, endothelin-1 was the most powerful prognostic marker among the variables tested (P = 0.0001). A multivariate model, including plasma atrial natriuretic peptide and noradrenaline, NYHA class, age, and echocardiographic left ventricular end-diastolic diameter index was highly predictive of mortality (P = 0.00008), but only endothelin-1 remained significantly associated with outcome (P = 0.02). Patients with plasma endothelin-1 > or = 5 pg. ml-1 had a higher mortality rate than those with endothelin-1 < 5 pg. ml-1 (21% vs 4%, P = 0.001). CONCLUSION: Our results suggest that elevated endothelin-1 plasma levels are associated with a poor prognosis and routine plasma endothelin-1 determination provides important prognostic information in mild to moderate heart failure.

Atrial Natriuretic Factor↗

Morphometric and metabolic profile of the distal segment of the internal mammary artery: caution on its use for coronary anastomoses.

OBJECTIVE: Elastic arteries were found to be less prone to intimal hyperplasia than muscular arteries. The internal mammary artery (IMA), which is elastic in its proximal segment, presents a gradual decrease of media elastic fibers along its downstream course. Metabolic and morphometric studies of the distal end of the IMA with regard to its local susceptibility to develop intimal changes were undertaken in order to evaluate the reliability of its use as an anastomotic site for bypass grafting. METHODS: Twenty distal segments of IMA were harvested from patients who had undergone myocardial revascularization. Histologic, enzyme-histochemical and morphometric studies were undertaken on these arterial segments. RESULTS: Histologic examinations indicated an elastomuscular structure in 13 patients, a muscular structure in 6 and an elastic structure in 1. Of the 20 IMAs, none was found to have intimal thickening of greater than 25% of the diameter of the lumen. The enzyme-histochemical profile of the proliferating cells found in the intimal thickening differed from normal contractile smooth muscle medial cells in the loss of myosin and mitochondrial ATPase, plasma membrane 5' nucleotidase, moderately decreased aerobic dehydrogenase and increased lactate dehydrogenase activity and ribonucleoprotein-linked pyroninophilia. Lysosomal beta-glucuronidase and sulfatase were strongly active. This enzyme behavior is unfavorable to contractile function and favorable to cell proliferation and lipid accumulation, two events strongly involved in the atherogenic process. CONCLUSION: Intimal proliferative changes were observed in the distal segment of the IMA. Although there was no histologic evidence of atherosclerotic plaque, the enzyme-histochemical profile of this intimal thickening was favorable to cell proliferation and lipid accumulation. These findings suggest that it may be beneficial to avoid coronary anastomoses with the distal end of the IMA and to use a more proximal/elastic segment.

5'-Nucleotidase↗

Prognostic significance of bacterial infection in bleeding cirrhotic patients: a prospective study.

BACKGROUND/AIMS: In cirrhotic patients, bacterial infection is frequently associated with gastrointestinal bleeding and seems to increase mortality. The aims of this study were to determine the incidence of bacterial infections in bleeding cirrhotic patients and the influence of infections on the risk of rebleeding and death. METHODS: Cirrhotic patients admitted for gastrointestinal bleeding who had not received antimicrobial chemotherapy in the previous 7 days were included. Blood, urine, and ascitic fluid cultures were systematically performed 1, 2, 4, and 7 days after admission. RESULTS: Sixty-four patients were enrolled. Forty-two bacterial infections were documented in 23 patients (36%) within 7 days of admission. In patients with bacterial infection, mean Child-Pugh score and mean number of blood units transfused were significantly higher, early rebleeding was more frequent (43.5% vs. 9.8%; P < 0.01), and 4-week mortality was higher (47.8% vs. 14.6%; P < 0.01). Multivariate analysis only identified bacterial infections as predictive of early rebleeding (P < 0.02) and a high Child-Pugh score as predictive of death (P < 0.001). CONCLUSIONS: In bleeding cirrhotic patients, bacterial infections only increase the risk of early rebleeding, and mortality is related to the severity of cirrhosis.

Adolescent↗

Cognitive function and assessment of lung function in the elderly.

The feasibility of spirometry or respiratory impedance measurements for assessing lung function in the elderly was compared in 208 institutionalized patients with various degrees of cognitive function impairment. Respiratory impedance was determined by the forced oscillation technique. Cognitive function was assessed by the score for the mini-mental state (MMS) examination. Of the 208 patients, 126 had severe cognitive impairment (MMS < or = 17), 36 had mild impairment (18 < or = MMS < or = 23), and 46 had no impairment (MMS > or = 24). Of the 208 patients, respiratory impedance measurements were possible in 159, whereas in only 85 was spirometry possible. The overall difference between the feasibility rates for the spirometric and respiratory impedance measurements was highly significant (chi 2 = 71.4; p < 10(-6)). The difference between the feasibility rates for the two techniques was higher in the group of subjects with severe cognitive impairment than in the groups with mild impairment and no impairment, respectively. Among the 84 patients able to complete both tests, significant correlations were found between the spirometric and respiratory impedance measurements. These results indicate that respiratory impedance measurement seems a more useful tool than spirometry for assessing lung function in elderly patients whenever cognitive function is impaired.

Aged↗

Electrophoretic study of the physico-chemical characteristics of Bence-Jones proteinuria and its association with kidney damage.

AIM: To identify a physico-chemical criterion, or set of criteria, explaining and possibly predicting the nephrotoxic behaviour of Bence-Jones proteins (BJP). METHODS: The electrophoretic mobility and isoelectric point (pI) of 92 BJP isolates were determined using various electrophoresis procedures on polyacrylamide gel. The proportions of monomers and dimers were determined using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS PAGE) in 58 cases. PAGE data for 10 BJP isolates were used to construct Ferguson plots and titration curves. RESULTS: The distribution of electrophoretic mobility and pI values was bimodal and showed a positive correlation when the pI was above 6. The values of these two parameters in 22 patients with renal impairment were not significantly different from those in the patients without renal impairment, and the statistical analysis showed no predictive value for the onset of renal impairment. However, patients excreting the lambda light chain isotype had a 2.8-fold higher risk of developing renal impairment compared with the other patients. Studies of the charge variation of the protein with pH indicated three types of behaviour, suggesting that the charge of BJP is highly variable at physiological pH. CONCLUSION: It is important to study not only the positivity or negativity of the BJP charge at a given pH, but also its intensity. The study of the BJP titration curves in patients with renal impairment suggests that a low charge at physiological urinary pH could predict renal impairment.

Aged↗

Clinical pharmacokinetics of zidovudine: inter and intraindividual variability and relationship to long term efficacy and toxicity.

The variability of the pharmacokinetics of zidovudine after its oral administration to 36 AIDS patients has been investigated by measuring the plasma and urine levels of zidovudine and its metabolite on Days 1 and 35 of continuous treatment. A two-phase absorption model was first defined from well-documented data in 12 subjects. The population characteristics of the kinetic parameters for both days were estimated by a nonparametric method. On Day 1, the mean (coefficient of variation) volume of distribution of zidovudine was 94.41 (90%), its mean half-life was 0.81 h (107%) and its mean oral clearance was 117 l.h-1 (57%) and on Day 35, these values were, respectively, 1121 (139%), 0.75 h (181%) and 295 l.h-1 (196%). The results confirm the large interindividual and intraindividual variation in zidovudine kinetics. The four covariates included in the population analysis (body weight, serum haemoglobin, creatinine and bilirubin) did not show clear relationship to the kinetic parameters. Thirty-four subjects were follow-up clinically for 99 days to 367 days after initiation of zidovudine therapy. The relationship between individual kinetic parameters (determined by Bayesian estimation), mean concentration profiles and outcome was studied through survival analysis. Long-term efficacy was defined as the prevention of opportunistic infections, which occurred in 13 patients. No clinical or kinetic variables, nor the individual zidovudine concentration profiles were found to predict the occurrence of an opportunistic infection. Toxicity was defined as a 20%-decrease in serum haemoglobin, which occurred in 13 patients. A significant relationship between mean daily concentration and toxicity was found, with an hazard of occurrence of toxicity 4.3-times larger when the mean steady stade concentration was 0.8 mg.l-1 than 0.6. The results indicate that zidovudine dosage should be individualised.

AIDS-Related Complex↗