Predictive graphical model, network-based medical tool for the prognosis of chronic hepatitis C patients treated with peg-interferon plus ribavirin.

BACKGROUND: There are few model networks to predict treatment outcome in viral hepatitis. AIM: To develop an easy bioinformatics platform based on algorithm decisions (Bayesian network) for a more efficient prediction of treatment response. METHODS: Totally 385 consecutive chronic hepatitis C (CHC) treated patients were included. More than 40 variables were analysed. Data from 308 patients were used to build the variable model network using DLIFE platform based on predictive graphical models. The prediction accuracy of the bioinformatics network was compared with the true data collected in a retrospective study. The model was then validated twice with external data from CHC patients treated in other hospitals. RESULTS: The accuracy of this bioinformatics network for treatment response in our 308 patients was 83.3%, which is higher than the accuracy obtained by physicians on the basis of study of clinical data and their own experience (50-65%). The receiver operator characteristic curve areas after validation with another cohort of patients were: 0.91 for sustained virological response, one for nonresponse, and 0.81 for relapse. DLIFE offered a diagnostic accuracy of 81.3%, which is a clear improvement compared with unassisted prognosis (50-65%). CONCLUSIONS: This bioinformatics platform (DLIFE) accurately predicts the outcome of CHC combination therapy, improving treatment decisions and reducing costs. This bioinformatics platform allows integrating widespread data sources and permits predicting the clinical outcome of a particular patient using a general predictive graphical model.

[High-frequency jet ventilation with the HFV 970 prototype in laryngeal microsurgery: comparison of 2 injection systems]. / Ventilación con jet a alta frecuencia con el prototipo HFV 970 en microcirugía laríngea: comparación entre dos sistemas de inyección.

OBJECTIVE: To describe the results obtained with the use of a high frequency jet ventilation system with the HFV 970 prototype through two types of injector, an intratracheal cannula and an endotracheal tube, in 12 patients undergoing laryngoscopic microsurgery. PATIENTS AND METHOD: After anesthetic induction with propofol and succinylcholine, an intratracheal cannula was placed in the patients in group A by way of cricothyroid membrane puncture. The tracheas of group B patients were intubated with a number 7 tube, through which was inserted the same type of cannula as had been used with group A patients. A prototype Servo HFV 970 respirator was used with the following protocol: minute volume 120 ml/min, inspiratory time 30%, respiratory rate 120 cycles/min and a FiO2 of 1. Anesthesia was maintained with propofol in continuous perfusion. The parameters studied were peak airway pressure, PCO2, PO2 and pH. Data were recorded at baseline and every 5 min thereafter until the end of surgery. RESULTS: During high frequency jet ventilation there were no statistically significant differences between groups A and B with respect to peak airway pressure. PCO2 in group A increased significantly during surgery, while in group B it decreased significantly. Oxygenation was excellent in both groups, being significantly higher than baseline values at all times studied, with no statistically significant differences between the 2 groups. CONCLUSION: Our results for the efficacy of ventilation and oxygenation with the prototype HFV 970 are similar to those published for conventional high frequency jet ventilation. Using a tracheal tube assures adequate ventilation, but supposes a tendency to entrapment, whereas use of an intratracheal cannula is associated with lower ventilatory efficacy and less entrapment. Oxygenation is excellent with both systems.

Conformational transition of insulin induced by n-alkyltrimethylammonium bromides in aqueous solution.

A surfactant-induced conformational transition of bovine insulin has been detected by difference spectroscopy for a homologous series of n-alkytrimethylammonium bromides, chain length C10-C16 at pH 10.0, 25 degrees C. The transition was followed as a function of surfactant concentration by absorbance measurements at 275 nm and the data were analysed to obtain the Gibbs energy of the transition in water (delta Gw degree) and in a hydrophobic environment (delta Ghc degree) for saturated protein-surfactant complexes. A value of delta Gw degree of -11.8 +/- 1.8 kJ mol-1 was found independent of n-alkyl chain length, which is similar to the value found for the n-alkylsulfate-induced transition in a previous study (-14.6 +/- 3.0 kJ mol-1). The values of delta Ghc degree were in the range approximately -88 to -100 kJ mol-1 for chain lengths from C10 to C16. The values of delta Ghc degree vs. chain length for both the n-alkyltrimethylammonium bromides and the n-alkylsulfates lie on the same curve, demonstrating that delta Ghc degree is independent of the nature of the surfactant head group.

Interaction between sodium n-undecyl sulfate and insulin.

The binding of sodium n-undecyl sulfate with bovine insulin was studied at pH 3.2 and 10 by equilibrium dialysis at 25 degrees C. The binding data have been used to determine the Gibbs energies of interaction using the theoretical model of the Wyman binding potential. The curves of Gibbs energies as a function of the number of bound ligands (v) tend to limiting values of around -14 kJ mol-1 at high values of v. The enthalpies of interaction have been measured directly by microcalorimetry showing an increase of exothermicity at lower pH. The results have been compared with similar data for the interaction of anionic surfactants with insulin.

Inactivation of yeast nucleotidyl transferase and its effect on the integrity of the aminoacid acceptor end of transfer RNA.

Yeast tRNA nucleotidyl transferase rapidly inactivates (half life c. 2 hr) upon nitrogen starvation of exponentially growing cells. The inactivation does not occur when glucose together with the nitrogen source is removed or when glucose is replaced by ethanol. The transferase activity reappears shortly after replenishment of the nitrogen source and this appearance of the enzymatic activity is blocked by cycloheximide, indicating the need for protein biosynthesis during the process. The nucleotidyl transferase activity is also very low in stationary phase yeast cells. A ten fold decrease in the transferase activity is not paralleled by loss of the integrity of the 3' end of the tRNA chains. It seems that there is a large excess of enzymatic activity over that needed to keep the tRNA chains complete. The observed lack of the 3' end of tRNAs from late stationary phase yeast cannot be accounted for by the observed drop in transferase activity in these cells.

Identification of an apparent aminoacyl-tRNA synthetase activator factor as tRNA nucleotidyltransferase.

The ability of yeast extracts to aminoacylate crude yeast tRNA with leucine and other amino acids is largely lost after chromatography of the extracts in DEAE-Sephadex. The original aminoacylating ability is restored by combining protein fractions from the DEAE-chromatogram. The characteristics of this reactivation are very similar to the activation, by protein factors, of certain aminoacyl-tRNA synthetases reported by others. The results in this work indicate that the apparent aminoacyl-tRNA synthetase activator factor is the tRNA nucleotidyltransferase and that the restoration of the original tRNA aminoacylating ability is a consequence of the repairing of the 3' end of incomplete tRNA chains.