Editorial: A light breakfast, a jug of salt water, and bowel.

Successful colonoscopy is predicated on achieving adequate colon cleansing. An ideal bowel preparation would be low in volume, acceptable to patients, reliable in cleansing efficacy, and safe. The study by Di Palma et al. in this issue shows that a novel, low-volume (960 ml) preparation of mixed sulfate salts can achieve excellent bowel cleansing with acceptable tolerability and minimal electrolyte shifts. A split-dosing strategy, with a proportion of the preparation administered on the day of colonoscopy, achieved a 97.2% preparation success rate vs. 82.4% using a regimen provided entirely the day before colonoscopy. These results were comparable with control groups using a commercially available polyethylene glycol solution. Endoscopists and patients alike should be encouraged by the trend toward lower-dose bowel cleansing regimens that achieve equivalent efficacy compared with large-volume preparations.

Randomized study comparing two regimens of oral sodium phosphates solution versus low-dose polyethylene glycol and bisacodyl.

PURPOSE: Low-volume bowel preparation regimens for colonoscopy are reported to improve patient acceptance and compliance. We sought to compare the bowel cleansing efficacy, tolerability, and acceptability of three low-volume regimens: an oral sodium phosphates solution 45/45 ml (NaP-45/45), a reduced-dose oral sodium phosphates solution 45/30 ml (NaP-45/30), and polyethylene glycol plus bisacodyl (PEG-2L). RESULTS: A total of 121 patients were evaluated (mean age 55.2 +/- 8.9 years). Bowel cleansings rated as excellent and good were significantly different among the groups: NaP-45/45 = 98%, NaP-45/30 = 88%, and PEG-2L = 76% (P < 0.04). Side effects were not significantly different except for greater thirst in the NaP-45/45 group (P = 0.001) and increased vomiting in females using PEG-2L (two-tailed interaction, P < 0.10). Willingness to retake the preparation was higher among the sodium phosphates regimens (88, 95, and 73%, respectively; P = 0.019). CONCLUSIONS: Better cleansing and willingness to retake the regimen was achieved with the oral sodium phosphates solutions than with polyethylene glycol plus bisacodyl.

Guidelines for the safe and effective use of sodium phosphate solution for bowel cleansing prior to colonoscopy.

Oral sodium phosphate solution is used worldwide as a bowel preparation for colonoscopy, surgery, and medical-imaging procedures. Although recent reports of adverse renal effects associated with sodium phosphate raise concern, sodium phosphate preparations remain safe and effective choices for patients who receive proper instruction for their use. Improper use of any bowel preparation can lead to complications. The purpose of this article is to provide a guide for selecting those patients for whom oral sodium phosphate solution is an appropriate bowel-cleansing choice and to review the importance of patient education, dosing, and hydration to help ensure that clinicians and patients use these preparations safely.

Robust regression for high throughput drug screening.

Effective analysis of high throughput screening (HTS) data requires automation of dose-response curve fitting for large numbers of datasets. Datasets with outliers are not handled well by standard non-linear least squares methods, and manual outlier removal after visual inspection is tedious and potentially biased. We propose robust non-linear regression via M-estimation as a statistical technique for automated implementation. The approach of finding M-estimates by Iteratively Reweighted Least Squares (IRLS) and the resulting optimization problem are described. Initial parameter estimates for iterative methods are important, so self-starting methods for our model are presented. We outline the software implementation, done in Matlab and deployed as an Excel application via the Matlab Excel Builder Toolkit. Results of M-estimation are compared with least squares estimates before and after manual editing.

Monotonicity of interleukin-1 receptor-ligand binding with respect to antagonist in the presence of decoy receptor.

We consider the interaction between interleukin-1 IL-1, its receptor IL-1RI, the receptor antagonist IL-1Ra and a decoy receptor (or trap) that binds both with the ligand and the antagonist. We study how the interaction between IL-1Ra and the decoy receptor influences the effect of either reagent on reducing the equilibrium concentration of the receptor-ligand complex. We obtain that, given a certain relationship among the equilibrium constants and the total concentrations of solutes, IL-1Ra can reverse the effect of the decoy receptor of decreasing the equilibrium concentration of the receptor-ligand complex. This finding derives from a mathematical result applicable to any reversible chemical reaction system comprising four species arranged in a square such that each species binds its two immediate neighbors. The result gives the monotonicity of the equilibrium concentrations of the complex species as functions of the total concentrations of the simple species.

Scan-rate-dependent melting transitions of interleukin-1 receptor (type II): elucidation of meaningful thermodynamic and kinetic parameters of aggregation acquired from DSC simulations.

The role of thermal unfolding as it pertains to thermodynamic properties of proteins and their stability has been the subject of study for more than 50 years. Moreover, exactly how the unfolding properties of a given protein system may influence the kinetics of aggregation has not been fully characterized. In the study of recombinant human Interleukin-1 receptor type II (rhuIL-1R(II)) aggregation, data obtained from size exclusion chromatography and differential scanning calorimetry (DSC) were used to model the thermodynamic and kinetic properties of irreversible denaturation. A break from linearity in the initial aggregation rates as a function of 1/T was observed in the vicinity of the melting transition temperature (T(m) approximately 53.5 degrees C), suggesting significant involvement of protein unfolding in the reaction pathway. A scan-rate dependence in the DSC experiment testifies to the nonequilibrium influences of the aggregation process. A mechanistic model was developed to extract meaningful thermodynamic and kinetic parameters from an irreversibly denatured process. The model was used to simulate how unfolding properties could be used to predict aggregation rates at different temperatures above and below the T(m) and to account for concentration dependence of reaction rates. The model was shown to uniquely identify the thermodynamic parameters DeltaC(P) (1.3 +/- 0.7 kcal/mol-K), DeltaH(m) (74.3 +/- 6.8 kcal/mol), and T(m) with reasonable variances.

Low volume bowel preparation for colonoscopy: randomized, endoscopist-blinded trial of liquid sodium phosphate versus tablet sodium phosphate.

OBJECTIVE: The aim of this study was to compare the colon-cleansing effectiveness, ease of consumption, and side effect profiles of two commercially available preparations of sodium phosphate: liquid Fleet Phospho-soda and Visicol tablets. METHODS: Outpatients undergoing elective colonoscopy were sequentially randomized to one of two preparation groups: liquid: 45 ml at 7:00 PM, 45 ml 3 h before colonoscopy; or tablet: 20 tablets at 7:00 PM, 20 tablets 3-5 h before colonoscopy. Subjects rated preparation tolerability on a 5-point Likert scale. A Residual Stool Score was calculated for each subject based on the amount of stool, consistency of residual stool, and percent of bowel visualized (range 0-11, 0 = best). The endoscopists were blinded to the preparation used. RESULTS: A total of 101 subjects were enrolled (43 male, 58 female, mean age 58.2 yr). The groups were similar in age and indications for colonoscopy. Overall, bowel cleansing was rated "Excellent" or "Good" in 92% of liquid preparation subjects, compared with 74% of tablet preparation subjects (p = 0.03). Subjects in the liquid group demonstrated significantly less residual stool than did tablet subjects (Residual Stool Scores: liquid 1.3 +/- 1.2 vs tablet 1.9 +/- 1.5, p < 0.05). Subjects rated the liquid preparation easier to swallow (p < 0.005) and more convenient to take (p < 0.005) than tablets. Among liquid subjects, 45 of 50 reported a willingness to take their preparation for future colonoscopies, compared with 36 of 49 who took tablet sodium phosphate (p < 0.04). CONCLUSIONS: Liquid sodium phosphate is better tolerated and more effective at colon cleansing when compared with sodium phosphate in tablet form.