A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study.

OBJECTIVE: To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN: A consensus developmental study. SETTING: International. POPULATION: Two hundred and five stakeholders completed the first round. METHODS: The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES: All outcomes were extracted from the literature. RESULTS: We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS: This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT: 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.

Oxygen-participated electrochemistry of new lithium-rich layered oxides Li3MRuO5 (M = Mn, Fe).

We describe the synthesis, crystal structure and lithium deinsertion-insertion electrochemistry of two new lithium-rich layered oxides, Li3MRuO5 (M = Mn, Fe), related to rock salt based Li2MnO3 and LiCoO2. The Li3MnRuO5 oxide adopts a structure related to Li2MnO3 (C2/m) where Li and (Li0.2Mn0.4Ru0.4) layers alternate along the c-axis, while the Li3FeRuO5 oxide adopts a near-perfect LiCoO2 (R3[combining macron]m) structure where Li and (Li0.2Fe0.4Ru0.4) layers are stacked alternately. Magnetic measurements indicate for Li3MnRuO5 the presence of Mn(3+) and low spin configuration for Ru(4+) where the itinerant electrons occupy a π*-band. The onset of a net maximum in the χ vs. T plot at 9.5 K and the negative value of the Weiss constant (θ) of -31.4 K indicate the presence of antiferromagnetic superexchange interactions according to different pathways. Lithium electrochemistry shows a similar behaviour for both oxides and related to the typical behaviour of Li-rich layered oxides where participation of oxide ions in the electrochemical processes is usually found. A long first charge process with capacities of 240 mA h g(-1) (2.3 Li per f.u.) and 144 mA h g(-1) (1.38 Li per f.u.) is observed for Li3MnRuO5 and Li3FeRuO5, respectively. An initial sloping region (OCV to ca. 4.1 V) is followed by a long plateau (ca. 4.3 V). Further discharge-charge cycling points to partial reversibility (ca. 160 mA h g(-1) and 45 mA h g(-1) for Mn and Fe, respectively). Nevertheless, just after a few cycles, cell failure is observed. X-ray photoelectron spectroscopy (XPS) characterisation of both pristine and electrochemically oxidized Li3MRuO5 reveals that in the Li3MnRuO5 oxide, Mn(3+) and Ru(4+) are partially oxidized to Mn(4+) and Ru(5+) in the sloping region at low voltage, while in the long plateau, O(2-) is also oxidized. Oxygen release likely occurs which may be the cause for failure of cells upon cycling. Interestingly, some other Li-rich layered oxides have been reported to cycle acceptably even with the participation of the O(2-) ligand in the reversible redox processes. In the Li3FeRuO5 oxide, the oxidation process appears to affect only Ru (4+ to 5+ in the sloping region) and O(2-) (plateau) while Fe seems to retain its 3+ state.

Local structure and lithium mobility in intercalated Li3Al(x)Ti(2-x)(PO4)3 NASICON type materials: a combined neutron diffraction and NMR study.

The structural features of intercalated Li3AlxTi2-x(PO4)3 compounds, with x = 0 and 0.2, have been deduced by Rietveld analysis of neutron diffraction (ND) patterns recorded between 100 and 500 K. The Li insertion decreases the symmetry from R3̄c to R3̄ in analyzed compounds. In pristine Li1+xAlxTi2-x(PO4)3 samples, Li occupies mainly six-fold M1 sites at ternary axes; but in lithiated Li3AlxTi2-x(PO4)3 samples, Li is located near M2 positions at M3/M3' four-fold coordinated sites. In both cases, Li arrangement minimizes electrostatic Li-Li repulsions. The insertion of lithium resulted in the reduction of Ti(4+) to Ti(3+) that shifts (7)Li, (27)Al and (31)P MAS-NMR resonances towards more positive chemical shifts, improving the resolution of different sites. The detection of twelve components in (7)Li MAS-NMR spectra recorded at room temperature suggests the location of Li(+) ions at three-oxygen faces that define M2 cavities. From (7)Li MAS-NMR spectra, the occupancy of sites and mobility of lithium were investigated in the temperature range 100-500 K. The correlation between structural information, deduced by neutron diffraction, and lithium mobility, deduced by NMR spectroscopy, provides new insights into structural factors that affect lithium mobility in materials with NASICON structure.

Structural factors that enhance lithium mobility in fast-ion Li(1+x)Ti(2-x)Al(x)(PO4)3 (0 ≤ x ≤ 0.4) conductors investigated by neutron diffraction in the temperature range 100-500 K.

Structural features responsible for lithium conductivity in Li(1+x)Ti(2-x)Al(x)(PO4)3 (x = 0, 0.2, and 0.4) samples have been investigated by Rietveld analysis of high-resolution neutron diffraction (ND) patterns. From structural analysis, variation of the Li site occupancies and atomic thermal factors have been deduced as a function of aluminum doping in the temperature range 100-500 K. Fourier map differences deduced from ND patterns revealed that Li ions occupy M1 sites and, to a lower extent, M3 sites, disposed around ternary axes. The occupation of M1 sites by Li ions is responsible for the preferential expansion of the rhombohedral R3c unit cell along the c axis with temperature. The occupation of less symmetric M3 sites decreases electrostatic repulsions among Li cations, favoring ion conductivity in Li(1+x)Ti(2-x)Al(x)(PO4)3 compounds. The variations detected on long-range lithium motions have been related to variations of the oxygen thermal factors with temperature. The information deduced by ND explains two lithium motion regimes deduced previously by (7)Li NMR and impedance spectroscopy.

Full structural and electrochemical characterization of Li2Ti6O13 as anode for Li-ion batteries.

A detailed structural and electrochemical study of the ion exchanged Li(2)Ti(6)O(13) titanate as a new anode for Li-ion batteries is presented. Subtle structural differences between the parent Na(2)Ti(6)O(13), where Na is in an eightfold coordinated site, and the Li-derivative, where Li is fourfold coordinated, determine important differences in the electrochemical behaviour. While the Li insertion in Na(2)Ti(6)O(13) proceeds reversibly the reaction of lithium with Li(2)Ti(6)O(13) is accompanied by an irreversible phase transformation after the first discharge. Interestingly, this new phase undergoes reversible Li insertion reaction developing a capacity of 170 mAh g(-1) at an average voltage of 1.7 V vs. Li(+)/Li. Compared with other titanates this result is promising to develop a new anode material for lithium ion rechargeable batteries. Neutron powder diffraction revealed that Na in Na(2)Ti(6)O(13) and Li in Li(2)Ti(6)O(13) obtained by Na/Li ion exchange at 325 °C occupy different tunnel sites within the basically same (Ti(6)O(13))(2-) framework. On the other hand, electrochemical performance of Li(2)Ti(6)O(13) itself and the phase released after the first full discharge is strongly affected by the synthesis temperature. For example, heating Li(2)Ti(6)O(13) at 350 °C produces a drastic decrease of the reversible capacity of the phase obtained after full discharge, from 170 mAh g(-1) to ca. 90 mAh g(-1). This latter value has been reported for Li(2)Ti(6)O(13) prepared by ion exchange at higher temperature.

Size evolution study of "molecular" and "atom-in-cluster" polarizabilities of medium-size gold clusters.

A study on static polarizabilities for a family of gold clusters (Au(n), n = 6, 12, 20, 34, 54) is presented. For each cluster, a density functional theory perturbation theory calculation was performed to compute the cluster polarizability and the polarizability of each atom in the cluster using Bader's "quantum theory of atoms in molecules" formalism. The cluster polarizability tensor, α(cluster), is expressed as a sum of the atom-in-molecule tensors, α(cluster)=∑(Ω)α(Ω). A strong quadratic correlation (R(2) = 0.98) in the isotropic polarizability of atoms in the cluster and their distance to the cluster center of mass was observed. The cluster polarizabilities are in agreement with previous calculations.

Transport of sugars and amino acids in the intestine: evidence for a common carrier.

D-Galactose, L-arginine, and their respective actively transported analogs are partially competitive inhibitors of the active transport of neutral amino acids in the small intestine of hamsters. Since the aforesaid classes of compounds are all transported by similar, sodium-ion-dependent mechanisms and elicit countertransport of each other, all may share a common, polyfunctional carrier in which a series of separate binding sites, namely, one each for sugars, neutral amino acids, basic amino acids, and Na(+) are joined together, as in a mosaic.

Virial theorem in the Kohn-Sham density-functional theory formalism: accurate calculation of the atomic quantum theory of atoms in molecules energies.

A new approach for computing the atom-in-molecule [quantum theory of atoms in molecule (QTAIM)] energies in Kohn-Sham density-functional theory is presented and tested by computing QTAIM energies for a set of representative molecules. In the new approach, the contribution for the correlation-kinetic energy (T(c)) is computed using the density-functional theory virial relation. Based on our calculations, it is shown that the conventional approach where atomic energies are computed using only the noninteracting part of the kinetic energy might be in error by hundreds of kJ/mol.

Chemisorption-repulsion energies of H2 on surface (110) of Mg1-xMx alloys (M = Al, Ni, Zn; 0.0 ≤ x ≤ 0.20) as a function of temperature.

In recent years, the popularity of metal hydrides has increased considerably for hydrogen storage and their applications in hydrogen fuel cells. Their potential applications for clean energy are promissory. However, the temperatures required for adsorption and desorption are extremely high, which range between 500 and 700 K, making their use impractical. To overcome these difficulties, the following work considers using three hydride alloys: magnesium-aluminum (MgAl), magnesium-nickel (MgNi), and magnesium-zinc (MgZn). The Mg concentrations were set to be between 80 and 100 wt% in order to reduce the temperatures of adsorption and desorption in contrast with the temperatures of pure magnesium. The chemisorption and repulsion energies of the hydrogen molecule on the surface (110) of the different metallic alloys were studied at 0, 200, 400, 600, and 700 K, respectively. The study was based on the density functional theory (DFT), with the module DMol3 of the molecular simulation program Materials Studio, which was used to obtain these energy values. The results confirm that adding aluminum, nickel, or zinc into magnesium matrix increases the chemisorption and decreases the energy repulsion values on surfaces of the metallic alloys, improving the effectiveness of the hydrogen storage.

Sudden deterioration in nonclassical infantile-onset Pompe disease responding to alglucosidase alfa infusion therapy: a case report.

A patient with atypical infantile Pompe disease suffered acute respiratory insufficiency at the age of 8 years which resulted in complete immobilization and dependence on assisted ventilation. Shortly after initiation of enzyme replacement therapy, she regained her mobility and, after 20 months of treatment, she now leads an almost normal life with limited restrictions.

Harmaline interaction with sodium-binding sites in intestinal brush border sucrase.

The effect of harmaline on rabbit brush border sucrase has been studied at pH 6.8. An initial analysis in classical kinetic terms revealed harmaline to be a fully competitive inhibitor of the substrate, sucrose. In spite of this result however, the following hypothesis has been tested. Harmaline, which is positively charged in the physiological range of pH, might in fact compete, not directly with the substrate site, but rather with an allosterically-related sodium-binding site which has been postulated to be involved in the activation of sucrase by the alkali-metal ions (Mahmood and Alvarado, Arch. Biochem. Biophys. 168, 585, 1975). Because of its size, harmaline, when bound to the metal site, could at least partially overlap with the substrate site, thereby behaving as if it were an authentic fully competitive inhibitor of the substrate. This hypothesis appears to be confirmed by the fact that the alkali metals can completely reverse the inhibition caused by harmaline.

Disaccharide uptake by brush-border membrane vesicles lacking the corresponding hydrolases.

Intestinal disaccharide uptake was studied with isolated brush-border membrane vesicles lacking the corresponding hydrolase. Either 15-day-old chick intestine, lacking both trehalase and lactase, or newborn pig intestine, lacking sucrase, was used. Both animal species yielded osmotically active vesicles capable of D-glucose/Na+ cotransport with a positive overshoot test. Vesicles from either origin gave quantitatively similar results in regard to both initial uptake rates and relative vesicle volumes. The nontransported analogs D-mannitol and L-glucose were used as diffusion markers. When tested with the appropriate disaccharidase-lacking vesicles, lactose, trehalose and sucrose exhibited uptake rates indistinguishable from those of D-mannitol and L-glucose. These uptakes were unaffected by the presence or absence of Na+, phlorizin and Tris. Chromatographic analysis confirmed the lack of hydrolysis of each disaccharide after prolonged incubation. The inescapable conclusion seems to be that intact disaccharides are not transported through the brush-border membrane, their uptake occurring through simple diffusion.

Quantitative analysis of the mixed activating effects of the alkali metal ions on intestinal brush-border sucrase at pH 5.2.

The activation of rabbit brush-border sucrase by the alkali metal ions, Li+, Na+ and K+, was analyzed using the equations of the random-order allosteric model previously proposed for sucrase (Mahmood, A. and Alvarado, F. (1975) Arch. Biochem. Biophys. 168, 585). The alkali metals have mixed activating effects in tert-butylamine buffers at pH 5.2, including: 1. Affinity-type activation, where the apparent Km decreases as a hyperbolic function of the metal concentration. 2. Capacity-type activation, where the apparent V increases with the metal concentration. These two effects were analyzed quantitatively: firstly, by using linear transformations that allowed us to solve each partial equation separately and secondly, by iteration of the general equation, which permits treating the mixed effects as a whole. Results are consistent with the interpretation that a single metal-binding (activator) site suffices to explain the simultaneous occurrence of the two types of kinetic effect. Nevertheless, complicating factors exist that may require the postulation of additional sites for monovalent cations. In particular, the tert-butylammonium ion appears to interface with the effects of the alkali metals, especially Li+.

Chloride transport in control and cystic fibrosis human skin fibroblast membrane vesicles.

Plasma membrane vesicles were isolated from either cystic fibrosis (CF) or non-CF cultured fibroblasts derived from skin biopsies of either foetus, child or adolescent human donors. The total membrane yield was essentially identical for either CF or control membranes. By using a rapid filtration technique, 36Cl uptake by these vesicles was quantitated in the absence and presence of alkali-metal ion-, electrical- and/or pH gradients. In the absence of a pH gradient (pHout = pHin = 7.5), Cl uptake took place downhill in both cases. Either cis K+, cis Na+ or an equimolar mixture of cis Na+ plus K+ caused Cl uptake activation. In the presence of an alkaline-inside pH gradient (pHout/pHin = 5.5/7.5), Cl uptake exhibited an apparent overshoot independently of the presence or absence of any metal-ion gradient. The observed potassium-, sodium- and proton-dependent Cl influx rates were all unaffected by voltage clamping, indicating the existence in these vesicles of electroneutral symport systems of the type Cl-/H+, Cl-/K+ and/or Cl-/Na+; but not 2 Cl-/Na+/K+. In the presence of an inward-directed K+ gradient, valinomycin further increased Cl uptake, both in the presence and in the absence of a pH gradient, indicating the presence of a rheogenic Cl uniport. In absolute quantitative terms, the two different modes (rheogenic and electroneutral) of Cl transport evinced in these vesicles were about 45% lower in CF than in control skin fibroblasts. However, qualitatively, there was no difference between normal and CF cells. The evidence obtained indicates that the CF defect, which is expressed in fibroblast plasma membranes, does not affect specifically either the rheogenic or the electroneutral Cl transport systems. Rather, the CF cells appear to give a smaller yield of closed, functional vesicles, reflected by a significantly smaller apparent intravesicular volume. Because it also affects the transport of D-glucose and L-alanine, this anomaly could be the consequence of a generalized membrane defect characterizing CF fibroblasts.

Trans-potassium effects on the chloride/proton symporter activity of guinea-pig ileal brush-border membrane vesicles.

To investigate the inhibitory effect of trans potassium on the Cl-/H+ symporter activity of brush-border membrane vesicles from guinea pig ileum, we measured both 36Cl uptake and, by the pyranine fluorescence method, proton fluxes, in the presence of appropriate H+ and K+ gradients. In the absence of valinomycin, a time-dependent inhibitory effect of chloride uptake by trans K+ was demonstrated. This inhibition was independent of the presence or absence of any K+ gradient. Electrical effects cannot be involved to explain these inhibitions because the intrinsic permeability of these vesicles to Cl- and K+ is negligibly small. Rather, our results show that, in the absence of valinomycin, the inhibitory effect of intravesicular K+ involves an acceleration of the rate of dissipation of the proton gradient through an electroneutral exchange of trans K+ for cis H+, catalyzed by the K+/H+ antiporter also present in these membranes. Valinomycin can further accelerate the rate of pH gradient dissipation by facilitating an electrically-coupled exchange between K+ and H+. To evaluate the apparent rate of pH-dissipating, downhill proton influx, we measured chloride uptake by vesicles preincubated in the presence of alkaline-inside pH gradients (pHout/pHin = 5.0/7.5), charged or not with K+. In the absence of intravesicular K+, proton influx exhibited monoexponential kinetics with a time constant k = 11 s-1. Presence of 100 mM K+ within the vesicles significantly increased the rate of pH gradient dissipation which, furthermore, became bi-exponential and revealed the appearance of an additional, faster proton influx component with k = 71 s-1. This new component we interpret as representing the sum of the electroneutral and the electrically-coupled exchange of trans K+ for cis H+, mentioned above. Finally, by using the pH-sensitive fluorophore, pyranine, we demonstrate that, independent of the absence or presence of a pH gradient, either vesicle acidification or alkalinisation can be generated by adding, respectively, Cl- or K+ to the extravesicular medium. Such results confirm the independent existence of both Cl-/H+ symporter and K+/H+ antiporter activities in our vesicle preparations, the relative activity of the former being larger under the conditions of the present experiments. The possible interplay of these two proton-transfer mechanisms in the regulation of the intracellular pH is discussed.

Characterization of the D-glucose/Na+ cotransport system in the intestinal brush-border membrane by using the specific substrate, methyl alpha-D-glucopyranoside.

By using isolated membrane vesicles, we have investigated the tenet that D-glucose transport across the intestinal brush-border membrane involves at least two distinct, Na+-activated agencies (D-glucose transport systems S-1 and S-2), only one of which (S-1) can use methyl alpha-D-glucopyranoside (methyl alpha-glucoside) as a substrate. Our results with this glucose analogue show that: (a) As a function of time, methyl alpha-glucoside uptake exhibits a typical overshoot, similar to but smaller than that given by D-glucose with the same vesicle batch. (b) Nonlinear regression analysis of substrate-saturation curves reveals that, contrary to D-glucose, methyl alpha-glucoside transport involves a single transport system which we have identified as S-1. (c) Methyl alpha-glucoside exhibits an apparent affinity (defined as the reciprocal of Km) 4-times smaller than that of D-glucose for S-1 (Km(Dglucose) = 0.5 mM; Km(methyl alpha-glucoside) = 2 mM). However, methyl alpha-glucoside has a Vmax (230 pmol/mg protein per s) identical to that characterizing D-glucose transport by this system. (d) In the absence of Na+, methyl alpha-glucoside uptake is indistinguishable from simple diffusion, confirming that Na+ is an obligatory activator of S-1. (e) Phlorizin behaves as a fully competitive inhibitor of methyl alpha-glucoside transport (Ki = 18 microM), again indicating that S-1 is involved. (f) Neither phloretin nor cytochalasin B affects methyl alpha-glucoside uptake. We conclude that methyl alpha-glucoside is a substrate specific for S-1, which permits study of the properties of this system without interference by substrate fluxes taking place through any other channel.

Usefulness of gastric intramucosal pH for monitoring hemodynamic complications in critically ill children.

OBJECTIVE: To assess the efficacy of gastric intramucosal pH for the evaluation of tissue perfusion and prediction of hemodynamic complications in critically ill children. DESIGN: Open prospective study without controls. SETTING: Pediatric intensive care unit (ICU) of a tertiary care university pediatric hospital. PATIENTS: Thirty critically ill children (16 boys and 14 girls), age range: 3 months-12 years. MEASUREMENTS AND RESULTS: A tonometry catheter was placed in the stomach of all patients on admission to the pediatric ICU. Simultaneous tonometry and arterial gas measurements were made on admittance and every 6-12 h throughout the study; a total of 202 measurements were made. The catheter was removed after extubation and/or when the patient was hemodynamically stable. Intramucosal pH was calculated using the Henderson-Hasselbalch equation based on the pCO2 of the tonometer and arterial bicarbonate. Intramucosal pH values between 7.30 and 7.45 were considered to be normal. The patient's condition was analyzed using the Pediatric Risk Mortality Score (PRISM). The relations between intramucosal pH and the presence of major hemodynamic complications (cardiopulmonary arrest, shock), minor hemodynamic complications (hypotension, hypovolemia or arrhythmia), death, PRISM score and the duration of the stay in the pediatric ICU were analyzed. Intramucosal pH on admission was 7.48 +/- 0.15 on average (range 7.04-7.68). Five patients (16%) had an intramucosal pH lower than 7.30 on admission; these patients did not have a higher incidence of hemodynamic complications. The 16 patients (53%) who had an intramucosal pH of less than 7.30 at some time during the course of their disease had more hemodynamic complications than the patients who did not have pH lower than 7.30 (p < 0.0001). Every case of cardiopulmonary arrest and shock was related to intramucosal pH of less than 7.30. Patients with major complications (cardiopulmonary arrest and shock) had lower intramucosal pHs than those with minor hemodynamic complications (p = 0.03); similarly, they had low intramucosal pH readings more often than those with minor complications (p = 0.0032). Intramucosal pH values less than 7.30 had a sensitivity of 90% and a specificity of 98% as a predictor of hemodynamic complications. There was no relation between intramucosal pH lower than 7.30 and either PRISM or the duration of the stay in the pediatric ICU. Patients with intramucosal pH less than 7.20 had a higher PRISM than the patients who did not have pH lower than 7.20 (p < 0.05). A patient who died during the study due to cardiopulmonary arrest had prior intramucosal pH measurements of 7.23 and 7.10, and three patients died of late complications after the end of the study. Hemodynamic complications were not detected with arterial pH. Gap pH (arterial pH-intramucosal pH) and standard pH measurements yielded the same results as gastric intramucosal pH. CONCLUSION: Intramucosal pH could provide a useful early indication of hemodynamic complications in critically ill children.

Analysis of costs in a pediatric ICU.

OBJECTIVE: To analyze the actual cost of pediatric intensive care and its different components, particularly the differences between various patient groups, with special reference to the variable cost and the elements included in it. DESIGN: Prospective, observational study. SETTING: Multidisciplinary 12-bed pediatric intensive care unit (PICU) in a tertiary university hospital. PATIENTS: 495 admissions to the unit over 17 consecutive months; 64.2% were medical patients and 35.8% were surgical patients; the mean (SE) stay in the PICU was 6.6 +/- 0.4 days. MEASUREMENTS AND RESULTS: The fixed cost per day per patient was calculated, including the costs of physicians, nurses, auxiliary and other personnel who worked during the study period, and the costs of structural depreciation, maintenance, consumption, and disposable material. The variable cost was individually calculated from the costs of routine procedures and also included expenditure on pharmaceuticals, blood products, biochemical, hematological, and bacteriologic tests, radiology, image diagnosis procedures, and other procedures. The Physiologic Stability Index (PSI) was obtained in the first 24 h after admission. The mean fixed cost per patient per day was u.s. $608, which represents 72% of the total patient cost during this study; 86% of this amount was for personnel (58% for nurses and auxiliary staff). Variable costs came to 28% of the total amount, and were $218 +/- 100 (M +/- SEM) per patient per day. In addition to the costs of their longer stay in the PICU, the daily variable costs of nonsurvivors were higher than those of survivors ($542 +/- 52 vs $179 +/- 7; p < 0.001). We classified the patients into four groups according to their PSI score in the first 24 h; variable daily costs increased (p < 0.05) in all comparisons with the PSI level: group I: < 4 points ($155 +/- 0.5), group II: 5-9 points ($210 +/- 13), group III: 10-14 points ($324 +/- 54), group IV: > 15 points ($480 +/- 42). However, this pattern was not found for all resources: the cost of treatment techniques and biochemical and hematological tests increased, but the consumption of antibiotics, parenteral nutrition, blood products, and bacteriologic tests reached their maximum level in groups I-III and radiology was not significantly influenced by PSI level. CONCLUSIONS: The cost of personnel was the biggest factor in intensive care costs: 62.4% of the total costs. Nonsurvivors generated 3 times the mean variable daily expenditure on survivors and had longer stays in the PICU. The increase in PSI score on the first day was associated with a global increase in variable costs. The cost of treatment techniques significantly increased as the illness became more severe but consumption of antibiotics and parenteral nutrition and use of bacteriologic tests and radiology did not.

Action of robenidine on the intestinal transport and digestion of nutrients in rabbit.

Robenidine is an anticoccidial guanidine used as an additive in rabbit fodder. Because its action is restricted to the small intestine, the present work addresses the question whether robenidine affects the growth of the animals, sugar and amino acid intestinal transport and membrane-bound intestinal digestion. For this purpose we have determined the intestinal transport of the substrates, and the enzymatic activity of neutral aminopeptidase and sucrase. We have found that robenidine diminishes the tissue accumulation of L-leucine and D-galactose at long incubation times, and increases the transepithelial mucosal to serosal flux of both substrates. These results suggest that robenidine may stimulate the enterocyte basolateral membrane flux of sugars and neutral amino acids. These results have been corroborated by means of isolated brush border and basolateral membrane vesicles. Apart from these effects, robenidine has also been shown to increase the enzymatic activity of neutral aminopeptidase and sucrase and thus resulting in a better digestion of nutrients.

Interactions between tryptophan, phenylalanine and sugar transport in the small intestinal mucosa.

The kinetics of the influx of tryptophan and phenylalanine into guinea-pig intestinal rings have been examined. The transfer of these two amino acids can be described by a single transport system, each amino acid having an affinity constant, Kt, of about 4 mM for the influx mechanism. Mutual inhibition studies have shown that the inhibitory constant of each of the amino acids is also 4 mM. Although fully competitive inhibition between the two amino acids occurs, the inhibition of the influx of the amino acids by sugars exhibits kinetics of the "pseudo-competitive" type. Such behaviour is compatible with an allosteric interaction between two different binding sites, one for each class of compounds. The lack of correlation between the inhibitory potency of a given sugar and its rate of transfer, as testified by a comparison of the effects of galactose and beta-methyl-glucoside on phenylalanine influx, can be reconciled with the "allosteric-interaction hypothesis", but specifically repudiates any theory that attempts to explain such interactions in a way that requires such a correlation. The fact that allosteric interactions are retained in cells preloaded with sodium also precludes a primary role for sodium in the mechanism of such interactions.