Assessment of QT(c)-prolonging potential of BX471 in healthy volunteers. A 'thorough QT study' following ICH E14 using various QT(c) correction methods.

Aims: Within the framework of the clinical development of BX471, this study was intended to provide experience in conducting 'thorough QT(c) studies' according to ICH E14. A broad range of QT correction methods and analysis strategies was employed. METHODS A double-blind, placebo- and positive-controlled, single-centre, three-way cross-over study was conducted in 74 healthy volunteers.

Persistent T1 hypointensity as an MRI marker for treatment efficacy in multiple sclerosis.

Background: MRI is often used as primary outcome measure in phase II clinical trials in multiple sclerosis (MS). Since persistent T1 hypointense lesions are a surrogate parameter for axonal damage and demyelination, they may serve as a marker for monitoring the efficacy of neuroprotective drugs. At present, a power analysis using black hole (BH) evolution as primary outcome measure has not been performed.

A complex plasma plant sterol locus on mouse chromosome 14 has at least two genes regulating intestinal sterol absorption.

We previously identified two inbred mouse strains, C57BL/6J and CASA/Rk, with different plasma plant sterol levels. An intercross between these strains revealed a broad plasma plant sterol locus on chromosome 14, which peaked at 17 centimorgan (cM) with a maximum logarithm of the odds score of 9.9.

Inclusion of MPA and in a rapid multi-drug LC-tandem mass spectrometric method for simultaneous determination of immunosuppressants.

Background: [corrected] Mycophenolic Acid (MPA) is often co-prescribed as part of a multiple immunosuppressant drug regimen. In this study an established LC-MS/MS method for the measurement of immunosuppressants cyclosporine A, tacrolimus, sirolimus and everolimus was optimized to include MPA without changing the sample pre-treatment and the LC-MS/MS configuration.

Methods: The sample pretreatment for EDTA-plasma was used as for whole blood.

Standardized approach to proteome profiling of human serum based on magnetic bead separation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Background: Magnetic bead purification for the analysis of low-abundance proteins in body fluids facilitates the identification of potential new biomarkers by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The aims of our study were to establish a proteome fractionation technique and to validate a standardized blood sampling, processing, and storage procedure for proteomic pattern analysis.

Methods: We used magnetic bead separation for proteome profiling of human blood by MALDI-TOF MS (mass range, 1000-10,000 Da) and studied the effects on the quality and reproducibility of the proteome analysis of anticoagulants, blood clotting, time and temperature of sample storage, and the number of freeze-thaw cycles of samples.

Rapid quantification of free and esterified phytosterols in human serum using APPI-LC-MS/MS.

A novel analytical platform based on liquid chromatography and tandem mass spectrometry using atmospheric pressure photoionization was applied for the simultaneous quantification of free and esterified beta-sitosterol, campesterol, brassicasterol, and stigmasterol. The total time for sample pretreatment and analysis could be reduced from approximately 3 h [gas chromatography-mass spectrometry (GC-MS)] to 15 min. The detection limits of the different phytosterols ranged between 0.

Rapid simultaneous quantification of immunosuppressants in transplant patients by turbulent flow chromatography combined with tandem mass spectrometry.

Background: Immunosuppressant therapeutic drug monitoring (TDM) is an important requirement in the management of post-transplant patients. Our aim was to develop and evaluate a robust high-throughput method using turbulent flow chromatography (TFC) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous quantification of cyclosporin A (CsA), tacrolimus (FK 506) and sirolimus.

Methods: A total of 1483 EDTA-blood pre-dosage samples from 147 kidney, 67 liver, 15 kidney/pancreas, and 48 bone marrow recipients were collected.

Population-based plasma kinetics of an oral dose of [2H4]retinyl acetate among preschool-aged, Peruvian children.

Background: The deuterated-retinol-dilution technique provides a quantitative estimate of total-body vitamin A (TBVA) stores in adults. To apply the technique to children, information on plasma retinol kinetics in this age group is needed.

Objectives: We described the plasma retinol kinetics of an oral dose of [(2)H(4)]retinyl acetate in a population of Peruvian children (12-24 mo of age) in order to examine the relation between TBVA stores and individual plasma isotopic ratios 3 d after the dose and to estimate 1) the time required for the isotope dose to mix with endogenous vitamin A, 2) the fractional catabolic rate for retinol, and 3) TBVA stores.

Acceptability, safety, and digestibility of spray-dried bovine serum added to diets of recovering malnourished children.

Background: Specially collected, spray-dried bovine and porcine blood plasma have been incorporated previously in feeds of weanling farm animals, resulting in increased dietary intakes and greater rates of weight gain than observed in control animals. Before conducting similar trials in human populations, preliminary studies have been completed to assess the acceptability, safety, and digestibility of processed animal plasma in young children.

Methods: Masked study diets were provided sequentially to each of ten young, Peruvian children recovering from severe protein-energy malnutrition during three randomly ordered 7-day dietary periods.

Protein requirements of infants and children: growth during recovery from malnutrition.

Objective: To evaluate the adequacy of protein intakes now recommended as safe for infants and toddlers.

Methods: Subjects were recovering malnourished infants, age 5.3 to 17.

Parallel optical image addition and subtraction in a dynamic photorefractive memory by phase-code multiplexing.

We propose and demonstrate experimentally a method for utilizing a dynamic phase-encoded photorefractive memory to realize parallel optical addition, subtraction, and inversion operations of stored images. The phase-encoded holographic memory is realized in photorefractive BaTiO(3), storing eight images using Walsh-Hadamard binary phase codes and an incremental recording procedure. By subsampling the set of reference beams during the recall operation, the selectivity of the phase address is decreased, allowing one to combine images in such a way that different linear combination of the images can be realized at the output of the memory.

Effect of milk-containing diets on the severity and duration of childhood diarrhea.

Individual components of milk from humans and other mammalian species may influence the severity, duration, and nutritional outcome of childhood diarrhea in different ways. Nonetheless, empirical data from clinical trials can be used to assess children's responses to specific milk-containing diets. Factors modifying the response to milk include its source, amount, frequency of feeding, type of processing, and accompanying foods, as well as the type and severity of enteric infection and specific characteristics of the host.

Post-prandial plasma aminograms in the assessment of protein quality for young children: maize and grain amaranth, alone and combined.

Post-prandial (p.p.) changes in plasma free amino acid (AA) concentrations of children consuming a single source of protein at critical levels are determined by its digestibility and total essential AA/total AA ratios; the molar proportion of the limiting EAA (EAA/TEAA), if any, will fall significantly in plasma as it is utilized more completely than others.

Quality-protein maize as the sole source of dietary protein and fat for rapidly growing young children.

Earlier studies demonstrated that quality protein maize (QPM), with increased lysine and tryptophan and decreased leucine contents, was more digestible and supported 45% greater nitrogen retention than common maize. Ten recovering malnourished children (ages 13 to 29 months, height-ages 5 to 15 months, weight-ages 3 to 11 months) have now received 90% of their diet energy and 100% of protein and fat from QPM. Energy intake was adjusted to allow them to reach the 50th centile of weight-for-length (according to the National Center for Health Statistics) in 90 days (two completed 60 days only).

[Base activity of glycogen phosphorylase b in human serum. Study of reference and discrimination values].

Serum glycogen phosphorylase activity as one of the sensitive indicators for the diagnosis of acute heart infarction was determined at 216 healthy probands using a standardized fluorometric procedure with a detection range from 0.03 to 6 nmol/s x l serum. Basal activity was averaged at 1.

Prediction of total daily fecal excretion during acute childhood diarrhea.

Clinical data from 133 male patients between 3 and 36 months of age were reviewed to identify factors that could predict high rates of fecal excretion during acute diarrhea. Diarrheal severity after hospitalization was measured by separate 4-h quantitative collections of feces during 6 days: the number of these 4-h collection periods with any stool output was used as an estimate of the number of bowel movements each day. The number of 4-h periods with any stool output was highly correlated with total fecal excretion expressed as grams per kilogram of body weight per day (p less than 0.

Quality protein maize: digestibility and utilization by recovering malnourished infants.

The opaque-2 gene was shown years ago to increase the nitrogen, lysine, and tryptophan contents of maize and to markedly increase its nutritional value for small children. Concerns about decreased yield, resistance, and acceptability discouraged further development of the gene. Quality protein maize, while retaining the opaque-2 characteristics, has overcome those constraints.

Effects of cassava variety and processing on energy and protein digestibility and utilization by young children.

Two varieties of cassava, processed as Nigerian fermented flour (gari) or as Brazilian flour (farinha), were fed to two groups of eight infants and young children, each group receiving both forms of one variety, with preceding, intervening and following casein control diets. The flours provided 50% of diet energy, with casein added to make 8% energy as protein, vegetable oils to make 20% as fat and corn syrup solids and sugar to make 72% carbohydrate (CHO) energy. Fecal wet weight increased (P less than 0.

Effect of continued oral feeding on clinical and nutritional outcomes of acute diarrhea in children.

One hundred twenty-eight nonmalnourished male patients between 3 and 36 months of age were randomly assigned to receive one of four lactose-free dietary treatments to determine the effect of dietary therapy on the severity and nutritional outcome of diarrheal illness. Group 1 received a formula diet composed of casein, sucrose, dextrin with maltose (Dextri-Maltose), and vegetable oil to provide 110 kcal/kg body weight/d (CSO-110). Group 2 received CSO to provide 55 kcal/kg/d (CSO-55) for 2 days and then CSO-110.

Nutritional value for young children of grain amaranth and maize-amaranth mixtures: effect of processing.

Amaranthus caudatus L. toasted flour, popped grain and flakes were each fed to nine young children as the source of all diet protein and fat and 50% of diet energy, preceded and followed by casein control diets. All provided 6.

[Hypertrophic cardiomyopathy with midventricular and subvalvular obstruction in both heart ventricles].

Typical (subaortic) and atypical (midventricular or apical) obstructions of both ventricles in HOCM are rare events. This combination could be demonstrated in a 21-year-old female patient by heart catheterization and angiocardiography. Simultaneous registration via 2 catheters in each ventricle showed pressure gradients with two steps in both ventricles: RV apical/RV midventricular 70-100 mm Hg, RV midventricular/subvalvular 25 mm Hg; LV apical/LV midventricular 70 mm Hg, LV midventricular/LV subvalvular 30 mm Hg; no valvular pressure gradients.