Decrease in serum procalcitonin levels over time during treatment of acute bacterial meningitis

INTRODUCTION: The aim of this study was to describe the change in serum procalcitonin levels during treatment for community-acquired acute bacterial meningitis. METHODS: Out of 50 consecutive patients presenting with bacterial meningitis and infection at no other site, and who had received no prior antibiotic treatment, 48 had a serum procalcitonin level above 0.5 ng/ml on admission and were enrolled in the study. RESULTS: The mean age of the patients was 55 years, and mean Glasgow Coma Scale score on admission was 13. The time from symptom onset to admission was less than 24 hours in 40% of the patients, 24–48 hours in 20%, and more than 48 hours in 40%. The median (interquartile) interval between admission and initial antibiotic treatment was 160 min (60–280 min). Bacterial infection was documented in 45 patients. Causative agents included Streptococcus pneumoniae (n = 21), Neisseria meningitidis (n = 9), Listeria monocytogenes (n = 6), other streptococci (n = 5), Haemophilus influenzae (n = 2) and other bacteria (n = 2). The initial antibiotic treatment was effective in all patients. A lumbar puncture performed 48–72 hours after admission in 34 patients showed sterilization of cerebrospinal fluid. Median (interquartile) serum procalcitonin levels on admission and at day 2 were 4.5 (2.8–10.8) mg/ml and 2 (0.9–5.0) mg/ml, respectively (P < 0.0001). The corresponding values for C-reactive protein were 120 (21–241) mg/ml and 156 (121–240) mg/ml, respectively. Five patients (10%) died from noninfectious causes during their hospitalization. CONCLUSIONS: Serum procalcitonin levels decrease rapidly with appropriate antibiotic treatment, diminishing the value of lumbar puncture performed 48–72 hours after admission to assess treatment efficacy

The surface properties of milk fat globules govern their interactions with the caseins: Role of homogenization and pH probed by AFM force spectroscopy

The surface of milk fat globules consists of a biological membrane rich in polar lipids and glycoproteins. However, high shear stress applied upon homogenization disrupts the membrane and leads to the adsorption of casein micelles, as the major protein fraction of milk. These changes in the interface properties could affect the interactions between native or homogenized milk fat globules and the surrounding protein matrix, at neutral pH and upon acidification. In this study, macroscale rheometry, microscopic observations, nanoscale AFM-based force spectroscopy and physico-chemical analysis were combined to examine the interfacial composition and structure of milk fat globules and to evaluate their interactions with casein micelles. We showed that the surface properties of milk fat globules (biological membrane vs. caseins) and pH govern their interactions with casein micelles. The adhesion between individual fat globules and casein micelles was higher upon homogenization, especially at acid pH where the work of adhesion increased from 3.3 x 10-18 to 14 x 10-18 J for native and homogenized fat globules, respectively. Consequently, casein-coated homogenized fat globules yield stiffer milk acid gels. These findings cast light on the importance of colloidal particle’s surface properties and pH on their connectivity with the surrounding matrix, which modulates the bulk microstructure and rheological properties with potential functional consequences, such as milk lipid digestion

Continuous infusion of ceftazidime in critically ill patients undergoing continuous venovenous haemodiafiltration: pharmacokinetic evaluation and dose recommendation

INTRODUCTION: In seriously infected patients with acute renal failure and who require continuous renal replacement therapy, data on continuous infusion of ceftazidime are lacking. Here we analyzed the pharmacokinetics of ceftazidime administered by continuous infusion in critically ill patients during continuous venovenous haemodiafiltration (CVVHDF) in order to identify the optimal dosage in this setting. METHOD: Seven critically ill patients were prospectively enrolled in the study. CVVHDF was performed using a 0.6 m(2 )AN69 high-flux membrane and with blood, dialysate and ultrafiltration flow rates of 150 ml/min, 1 l/hour and 1.5 l/hour, respectively. Based on a predicted haemodiafiltration clearance of 32.5 ml/min, all patients received a 2 g loading dose of ceftazidime, followed by a 3 g/day continuous infusion for 72 hours. Serum samples were collected at 0, 3, 15 and 30 minutes and at 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours; dialysate/ultrafiltrate samples were taken at 2, 8, 12, 24, 36 and 48 hours. Ceftazidime concentrations in serum and dialysate/ultrafiltrate were measured using high-performance liquid chromatography. RESULTS: The mean (± standard deviation) elimination half-life, volume of distribution, area under the concentration-time curve from time 0 to 72 hours, and total clearance of ceftazidime were 4 ± 1 hours, 19 ± 6 l, 2514 ± 212 mg/h per l, and 62 ± 5 ml/min, respectively. The mean serum ceftazidime steady-state concentration was 33.5 mg/l (range 28.8–36.3 mg/l). CVVHDF effectively removed continuously infused ceftazidime, with a sieving coefficient and haemodiafiltration clearance of 0.81 ± 0.11 and 33.6 ± 4 mg/l, respectively. CONCLUSION: We conclude that a dosing regimen of 3 g/day ceftazidime, by continuous infusion, following a 2 g loading dose, results in serum concentrations more than four times the minimum inhibitory concentration for all susceptible pathogens, and we recommend this regimen in critically ill patients undergoing CVVHDF

On how k-casein affects the interactions between the heat-induced whey protein/k-casein complexes and the casein micelles during the acid gelation of skim milk

Heat treatment of milk at 85–95 °C has long been reported to increase the pH of gelation and firmness of acid milk gels; hence its wide application in yoghurt manufacture. These changes have been attributed to the formation of heat-induced whey protein/κ-casein complexes in the milk, to which heat-denatured whey protein ingredients may be substituted. However, variations in resulting gels show that a possible role of κ-casein in determining the functional acid-gelation property of the complexes needs investigating. Model heat-induced whey protein/κ-casein complexes were produced of κ-casein content from 0 to 40% (w/w), but of similar size, secondary structure, surface hydrophobicity and thiol/disulphide distribution. These complexes were added to whey protein-free skim milk systems and the resulting acid-gelation behaviour of the milks was evaluated. The results showed a modification of the pH of gelation that was explained more by variation of the pI of complexes than by the κ-casein content

On how heat-induced whey protein/κ-casein complexes affect interactions during the acid gelation of milk

Heat treatment of milk at 85–95 °C has long been reported to increase the pH of gelation and firmness of acid milk gels; hence its wide application in yoghurt manufacture. These changes have been attributed to the formation of heat-induced whey protein/κ-casein complexes in the milk, to which heat-denatured whey protein ingredients may be substituted. However, variations in resulting gels show that a possible role of κ-casein in determining the functional acid-gelation property of the complexes needs investigating. Model heat-induced whey protein/κ-casein complexes were produced of κ-casein content from 0 to 40% (w/w), but of similar size, secondary structure, surface hydrophobicity and thiol/disulphide distribution. These complexes were added to whey protein-free skim milk systems and the resulting acid-gelation behaviour of the milks was evaluated. The results showed a modification of the pH of gelation that was explained more by variation of the pI of complexes than by the κ-casein content

The interfacial properties of milk fat globules govern their interactions with proteins: role of high shear stress and pH probed by AFM based force spectroscopy

The interfacial properties of colloidal particles influence their interaction with each other and with their environment. This, in turn, governs the physical and functional characteristics of colloidal systems such as emulsions found in foods, drugs or cosmetics.Milk has been an important part of the human diet for thousands of years. It is a natural oil-in-water emulsion in which the lipids are dispersed as ~0.1-10 μm colloidal assemblies called the milk fat globules (MFG). MFG are composed of a core droplet of triacylglycerols (TAG) surrounded by a biological membrane. This membrane, mainly composed of polar lipids, cholesterol and glycoproteins, acts as the interface with the surrounding bulk of milk proteins (ie. casein micelles and whey proteins) or with enzymes of the gastrointestinal tract during digestion. The physicochemical properties of MFG and their membrane composition are altered by technological treatments during the manufacture of dairy products (Lopez et al., 2015, Dairy Science & Technology). Shear stress induces the adsorption of caseins from the aqueous phase of milk to the MFG surface and heat-treatment causes the co-adsorption of highly-reactive denatured whey proteins. All these proteins precipitate at acid pH, which is used for milk gelation in yoghurt-making.Here, atomic force spectroscopy was used to measure the adhesion forces, adhesion work and rupture distances between individual casein micelles, attached to the AFM probe, and MFG taken at different stages of processing: native MFG, then processed MFG, prior to and after acidification.Results showed that native MFG present low affinity for casein micelles independently of the pH, due to the steric effect of the glycocalyx surrounding their native membrane. When casein were adsorbed to the MFG’s surface, the adhesion forces increased, particularly at acid pH due to a decrease in electrostatic repulsion. The presence of denatured whey proteins further enhanced adhesion between the MFG and individual casein micelles.These results evidenced a clear correlation between adhesion forces at the nanoscale and the bulk properties of the milk gels. This showed that the interfacial properties of MFG are important to drive the connectivity of the acid gel. This study open perspectives for the closer evaluation of individual colloid interface properties in relationship with the bulk physical and functional properties of colloid systems

The interfacial properties of milk fat globules govern their interactions with proteins: role of high shear stress and pH probed by AFM based force spectroscopy

The interfacial properties of colloidal particles influence their interaction with each other and with their environment. This, in turn, governs the physical and functional characteristics of colloidal systems such as emulsions found in foods, drugs or cosmetics.Milk has been an important part of the human diet for thousands of years. It is a natural oil-in-water emulsion in which the lipids are dispersed as ~0.1-10 μm colloidal assemblies called the milk fat globules (MFG). MFG are composed of a core droplet of triacylglycerols (TAG) surrounded by a biological membrane. This membrane, mainly composed of polar lipids, cholesterol and glycoproteins, acts as the interface with the surrounding bulk of milk proteins (ie. casein micelles and whey proteins) or with enzymes of the gastrointestinal tract during digestion. The physicochemical properties of MFG and their membrane composition are altered by technological treatments during the manufacture of dairy products (Lopez et al., 2015, Dairy Science & Technology). Shear stress induces the adsorption of caseins from the aqueous phase of milk to the MFG surface and heat-treatment causes the co-adsorption of highly-reactive denatured whey proteins. All these proteins precipitate at acid pH, which is used for milk gelation in yoghurt-making.Here, atomic force spectroscopy was used to measure the adhesion forces, adhesion work and rupture distances between individual casein micelles, attached to the AFM probe, and MFG taken at different stages of processing: native MFG, then processed MFG, prior to and after acidification.Results showed that native MFG present low affinity for casein micelles independently of the pH, due to the steric effect of the glycocalyx surrounding their native membrane. When casein were adsorbed to the MFG’s surface, the adhesion forces increased, particularly at acid pH due to a decrease in electrostatic repulsion. The presence of denatured whey proteins further enhanced adhesion between the MFG and individual casein micelles.These results evidenced a clear correlation between adhesion forces at the nanoscale and the bulk properties of the milk gels. This showed that the interfacial properties of MFG are important to drive the connectivity of the acid gel. This study open perspectives for the closer evaluation of individual colloid interface properties in relationship with the bulk physical and functional properties of colloid systems

Weaning from mechanical ventilation with pressure support in patients failing a T-tube trial of spontaneous breathing.

International audienceOBJECTIVE: Evidence that PS may facilitate weaning from mechanical ventilation (MV), although not confirmed by randomized trials, prompted us to investigate whether patients could be weaned with PS after failing a T-tube trial. DESIGN AND SETTING: This was a prospective, non-randomized study in two French intensive care units. PATIENTS AND PARTICIPANTS: One hundred eighteen patients were enrolled and underwent a T-tube trial, after which 87 were extubated. Thirty-one underwent a further trial with PS, after which 21 were extubated. INTERVENTIONS: All patients under MV >24 h meeting the criteria for a weaning test underwent a 30-min T-tube trial. If this was successful, they were immediately extubated. Otherwise, a 30-min trial with +7 cm H2O PS was initiated with an individualized pressurization slope and trigger adjustment. If all weaning criteria were met, the patients were extubated; otherwise, MV was reinstated. MEASUREMENTS AND RESULTS: The extubation failure rate at 48 h did not differ significantly between the groups: 11/87 (13%) versus 4/21 (19%), P=0.39. The groups were comparable with regard to endotracheal tube diameter, MV duration, the use of non-invasive ventilation (NIV) after extubation, initial severity score, age and underlying pathology, except for COPD. A significantly higher percentage of patients with COPD was extubated after the trial with PS (8/21-38%) than after a single T-tube trial (11/87-13%) (P=0.003). CONCLUSIONS: Of the patients, 21/118 (18%) could be extubated after a trial with PS, despite having failed a T-tube trial. The reintubation rate was not increased. This protocol may particularly benefit patients who are most difficult to wean, notably those with COPD

Mixing milk, egg and plant resources to obtain safe and tasty foods with environmental and health benefits

International audienceBackground: Since the early 1990s, major health and environmental concerns have developed and driven the emergence of diets involving a lower consumption of animal products. However, the transition towards greener diets is being hampered by the poor acceptance of vegan foodstuffs among western consumers. Mixed animal/ plant alternatives to familiar dairy or egg products offer a new field of innovation. Scope and approach: This review focuses on innovative mixes of egg or milk with plant ingredientsespecially legumesto develop products in which interactions between animal and plant are not usually expected, such as dairy or egg gels, emulsions or foams. The opportunities offered by such products in terms of consumer acceptance, nutrition, digestibility and techno-functional properties are reviewed and discussed with respect to their risk-benefit ratios. Key findings and conclusions: In many cases, animal/plant mixes offer enhanced protein stability and synergistic interfacial or textural properties that make them a flexible tool for food design. Fermentation offers important prospects for the nutritional and sensorial enhancement of animal/plant mixes, through the multi-criteria application of microbial consortia. Animal/plant mixes enable reduction in animal protein consumption while preserving amino acid and micronutrient intakes and sensory properties. However, their acceptability to consumers and society will also depend on controlled safety, especially regarding allergies or contaminants, on affordability, their degree of novelty or (ultra)processing, their actual environmental footprint and whether they meet consumer expectations for innovative foods in the transition towards greener diets