Effect of hydration status on cerebral blood flow and cerebrospinal fluid lactic acidosis in rabbits with experimental meningitis

The effects of hydration status on cerebral blood flow (CBF) and development of cerebrospinal fluid (CSF) lactic acidosis were evaluated in rabbits with experimental pneumococcal meningitis. As loss of cerebrovascular autoregulation has been previously demonstrated in this model, we reasoned that compromise of intravascular volume might severely affect cerebral perfusion. Furthermore, as acute exacerbation of the inflammatory response in the subarachnoid space has been observed after antibiotic therapy, animals were studied not only while meningitis evolved, but also 4-6 h after treatment with antibiotics to determine whether there would also be an effect on CBF. To produce different levels of hydration, animals were given either 50 ml/kg per 24 h of normal saline ("low fluid") or 150 ml/kg 24 h ("high fluid"). After 16 h of infection, rabbits that were given the lower fluid regimen had lower mean arterial blood pressure (MABP), lower CBF, and higher CSF lactate compared with animals that received the higher fluid regimen. In the first 4-6 h after antibiotic administration, low fluid rabbits had a significant decrease in MABP and CBF compared with, and a significantly greater increase in CSF lactate concentration than, high fluid rabbits. This study suggests that intravascular volume status may be a critical variable in determining CBF and therefore the degree of cerebral ischemia in meningitis.

Restrictive deferred hydration combined with preemptive norepinephrine infusion during radical cystectomy reduces postoperative complications and hospitalization time: a randomized clinical trial.

BACKGROUND Anesthetics and neuraxial anesthesia commonly result in vasodilation/hypotension. Norepinephrine counteracts this effect and thus allows for decreased intraoperative hydration. The authors investigated whether this approach could result in reduced postoperative complication rate. METHODS In this single-center, double-blind, randomized, superiority trial, 166 patients undergoing radical cystectomy and urinary diversion were equally allocated to receive 1 ml·kg·h of balanced Ringer's solution until the end of cystectomy and then 3 ml·kg·h until the end of surgery combined with preemptive norepinephrine infusion at an initial rate of 2 µg·kg·h (low-volume group; n = 83) or 6 ml·kg·h of balanced Ringer's solution throughout surgery (control group; n = 83). Primary outcome was the in-hospital complication rate. Secondary outcomes were hospitalization time, and 90-day mortality. RESULTS In-hospital complications occurred in 43 of 83 patients (52%) in the low-volume group and in 61 of 83 (73%) in the control group (relative risk, 0.70; 95% CI, 0.55-0.88; P = 0.006). The rates of gastrointestinal and cardiac complications were lower in the low-volume group than in the control group (5 [6%] vs. 31 [37%]; relative risk, 0.16; 95% CI, 0.07-0.39; P < 0.0001 and 17 [20%] vs. 39 [48%], relative risk, 0.43; 95% CI, 0.26-0.60; P = 0.0003, respectively). The median hospitalization time was 15 days [range, 11, 27d] in the low-volume group and 17 days [11, 95d] in the control group (P = 0.02). The 90-day mortality was 0% in the low-volume group and 4.8% in the control group (P = 0.12). CONCLUSION A restrictive-deferred hydration combined with preemptive norepinephrine infusion during radical cystectomy and urinary diversion significantly reduced the postoperative complication rate and hospitalization time.

Intraoperative Continuous Norepinephrine Infusion Combined with Restrictive Deferred Hydration Significantly Reduces the Need for Blood Transfusion in Patients Undergoing Open Radical Cystectomy: Results of a Prospective Randomised Trial

BACKGROUND Open radical cystectomy (ORC) is associated with substantial blood loss and a high incidence of perioperative blood transfusions. Strategies to reduce blood loss and blood transfusion are warranted. OBJECTIVE To determine whether continuous norepinephrine administration combined with intraoperative restrictive hydration with Ringer's maleate solution can reduce blood loss and the need for blood transfusion. DESIGN, SETTING, AND PARTICIPANTS This was a double-blind, randomised, parallel-group, single-centre trial including 166 consecutive patients undergoing ORC with urinary diversion (UD). Exclusion criteria were severe hepatic or renal dysfunction, congestive heart failure, and contraindications to epidural analgesia. INTERVENTION Patients were randomly allocated to continuous norepinephrine administration starting with 2 μg/kg per hour combined with 1 ml/kg per hour until the bladder was removed, then to 3 ml/kg per hour of Ringer's maleate solution (norepinephrine/low-volume group) or 6 ml/kg per hour of Ringer's maleate solution throughout surgery (control group). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Intraoperative blood loss and the percentage of patients requiring blood transfusions perioperatively were assessed. Data were analysed using nonparametric statistical models. RESULTS AND LIMITATIONS Total median blood loss was 800 ml (range: 300-1700) in the norepinephrine/low-volume group versus 1200 ml (range: 400-2800) in the control group (p<0.0001). In the norepinephrine/low-volume group, 27 of 83 patients (33%) required an average of 1.8 U (±0.8) of packed red blood cells (PRBCs). In the control group, 50 of 83 patients (60%) required an average of 2.9 U (±2.1) of PRBCs during hospitalisation (relative risk: 0.54; 95% confidence interval [CI], 0.38-0.77; p=0.0006). The absolute reduction in transfusion rate throughout hospitalisation was 28% (95% CI, 12-45). In this study, surgery was performed by three high-volume surgeons using a standardised technique, so whether these significant results are reproducible in other centres needs to be shown. CONCLUSIONS Continuous norepinephrine administration combined with restrictive hydration significantly reduces intraoperative blood loss, the rate of blood transfusions, and the number of PRBC units required per patient undergoing ORC with UD.

Vibronic Spectra of Jet-Cooled 2-Aminopurine center dot H2O Clusters Studied by UV Resonant Two-Photon Ionization Spectroscopy and Quantum Chemical Calculations

For understanding the major- and minor-groove hydration patterns of DNAs and RNAs, it is important to understand the local solvation of individual nucleobases at the molecular level. We have investigated the 2-aminopurine center dot H2O. monohydrate by two-color resonant two-photon ionization and UV/UV hole-burning spectroscopies, which reveal two isomers, denoted A and B. The electronic spectral shift delta nu of the S-1 <- S-0 transition relative to bare 9H-2-aminopurine (9H-2AP) is small for isomer A (-70 cm(-1)), while that of isomer B is much larger (delta nu = 889 cm(-1)). B3LYP geometry optimizations with the TZVP basis set predict four cluster isomers, of which three are doubly H-bonded, with H2O acting as an acceptor to a N-H or -NH2 group and as a donor to either of the pyrimidine N sites. The "sugar-edge" isomer A is calculated to be the most stable form with binding energy D-e = 56.4 kJ/mol. Isomers B and C are H-bonded between the -NH2 group and pyrimidine moieties and are 2.5 and 6.9 kJ/mol less stable, respectively. Time-dependent (TD) B3LYP/TZVP calculations predict the adiabatic energies of the lowest (1)pi pi* states of A and B in excellent agreement with the observed 0(0)(0) bands; also, the relative intensities of the A and B origin bands agree well with the calculated S-0 state relative energies. This allows unequivocal identification of the isomers. The R2PI spectra of 9H-2AP and of isomer A exhibit intense low-frequency out-of-plane overtone and combination bands, which is interpreted as a coupling of the optically excited (1)pi pi* state to the lower-lying (1)n pi* dark state. In contrast, these overtone and combination bands are much weaker for isomer B, implying that the (1)pi pi* state of B is planar and decoupled from the (1)n pi* state. These observations agree with the calculations, which predict the (1)n pi* above the (1)pi pi* state for isomer B but below the (1)pi pi* for both 9H-2AP and isomer A.

Engineering Tocopherol Selectivity in alpha-TTP: A Combined In Vitro/In Silico Study

"We present a combined in vitro/in silico study to determine the molecular origin of the selectivity of a-tocopherol transfer" "protein (a-TTP) towards a-tocopherol. Molecular dynamics simulations combined to free energy perturbation calculations predict a binding free energy for a-tocopherol to a-TTP 8.26+2.13 kcal mol{1 lower than that of c-tocopherol. Our calculations show that c-tocopherol binds to a-TTP in a significantly distorted geometry as compared to that of the natural ligand. Variations in the hydration of the binding pocket and in the protein structure are found as well. We propose a mutation, A156L, which significantly modifies the selectivity properties of a-TTP towards the two tocopherols. In particular, our simulations predict that A156L binds preferentially to c-tocopherol, with striking structural similarities to the wild-type- a-tocopherol complex. The affinity properties are confirmed by differential scanning fluorimetry as well as in vitro competitive binding assays. Our data indicate that residue A156 is at a critical position for determination of the selectivity of a-TTP. The engineering of TTP mutants with modulating binding properties can have potential impact at industrial level for easier purification of single tocopherols from vitamin E mixtures coming from natural oils or synthetic processes. Moreover," "the identification of a c-tocopherol selective TTP offers the possibility to challenge the hypotheses for the evolutionary development of a mechanism for a-tocopherol selection in omnivorous animals."

Continuous or repeated prolonged cisplatin infusions in children: a prospective study on ototoxicity, platinum concentrations, and standard serum parameters

BACKGROUND: To overcome the ototoxicity of cisplatin, single bolus infusions were replaced by repeated prolonged infusions of lower doses or by continuous infusions at still lower infusion rates. However, considering ototoxicity little is, in fact, known about the tolerance of repeated prolonged or continuous infusion in children. PROCEDURE: Auditory function was monitored along with plasma concentrations of free and total platinum (Pt), and with standard serum parameters (sodium, potassium, calcium, magnesium, phosphate, chloride, and creatinine) in 24 children receiving cisplatin by continuous infusion for the treatment of neuroblastoma and osteosarcoma or by repeated 1 or 6 hr infusions for the treatment of germ cell tumors. RESULTS: Hearing deteriorated in 10/15 osteosarcoma patients, 2/3 neuroblastoma patients, and 1/6 patients with germ cell tumors. Ototoxicity occurred after cumulative doses between 120 and 360 mg/m(2) cisplatin. In osteosarcoma patients, ototoxicity was associated with a comparatively higher mean plasma concentration of free Pt. However, Pt plasma concentrations did not discriminate between patients with or without ototoxicity. In patients experiencing ototoxicity serum creatinine increased by 45% compared to pre-treatment levels (mean). Serum creatinine increased by 26% in patients without ototoxicity (P < 0.05, Mann-Whitney Rank sum test). Despite standardized hydration, discrete but significant changes of potassium, sodium, magnesium, and phosphate were observed during and/or after cisplatin infusion, which, however, did not discriminate between patients with and without ototoxicity. CONCLUSIONS: While continuous cisplatin infusions are less nephrotoxic than repeated prolonged infusions, we observed considerable ototoxicity in patients treated with continuous cisplatin infusions, which necessitates further evaluations on the tolerance of continuous cisplatin infusions in children.

ESPEN Guidelines on Parenteral Nutrition: geriatrics

Older subjects are at increased risk of partial or complete loss of independence due to acute and/or chronic disease and often of concomitant protein caloric malnutrition. Nutritional care and support should be an indispensable part of their management. Enteral nutrition is always the first choice for nutrition support. However, when patients cannot meet their nutritional requirements adequately via the enteral route, parenteral nutrition (PN) is indicated. PN is a safe and effective therapeutic procedure and age per se is not a reason to exclude patients from this treatment. The use of PN should always be balanced against a realistic chance of improvement in the general condition of the patient. Lower glucose tolerance, electrolyte and micronutrient deficiencies and lower fluid tolerance should be assumed in older patients treated by PN. Parenteral nutrition can be administered either via peripheral or central veins. Subcutaneous administration is also a possible solution for basic hydration of moderately dehydrated subjects. In the terminal, demented or dying patient the use of PN or hydration should only be given in accordance with other palliative treatments.

[Urinary specific gravity--comparative measurements using reagent strips and refractometer in 340 morning urine samples]

The specific gravity of urine (SG) indicates the number and weight of solute particles in urine; its measurement is helpful in interpreting proteinuria detected by dipstick tests and in monitoring adequate hydration in patients with nephrolithiasis. Four methods for measuring SG or osmolality of urine are currently available (depression of the freezing-point, urometry, refractometry, cation exchange on a reagent strip). Using a recently developed reagent strip, we have measured SG in morning urines of 340 non-selected outpatients and compared the results with SG measurements by refractometry of the same urines. In 86.2% of all urines, a good positive correlation between SG measured by reagent strip and refractometry was noted (r = 0.913, p = 0.0001). In 13.8% of the urines, however, the SG measured by reagent strip deviated by more than +/- 5 from the value obtained by refractometry; in 90% of these urines, glucosuria (reagent strip values too low or too high), proteinuria (values too high), or bacteriuria/leukocyturia (values too low or too high) could be found. In alkaline urine (pH > 7.0), SG values obtained by reagent strip have to be corrected by +5.

Prediction of water–rock interaction and porosity evolution in a granitoid-hosted enhanced geothermal system, using constraints from the 5 km Basel-1 well

Numerical simulations based on plans for a deep geothermal system in Basel, Switzerland are used here to understand chemical processes that occur in an initially dry granitoid reservoir during hydraulic stimulation and long-term water circulation to extract heat. An important question regarding the sustainability of such enhanced geothermal systems (EGS), is whether water–rock reactions will eventually lead to clogging of flow paths in the reservoir and thereby reduce or even completely block fluid throughput. A reactive transport model allows the main chemical reactions to be predicted and the resulting evolution of porosity to be tracked over the expected 30-year operational lifetime of the system. The simulations show that injection of surface water to stimulate fracture permeability in the monzogranite reservoir at 190 °C and 5000 m depth induces redox reactions between the oxidised surface water and the reduced wall rock. Although new calcite, chlorite, hematite and other minerals precipitate near the injection well, their volumes are low and more than compensated by those of the dissolving wall-rock minerals. Thus, during stimulation, reduction of injectivity by mineral precipitation is unlikely. During the simulated long-term operation of the system, the main mineral reactions are the hydration and albitization of plagioclase, the alteration of hornblende to an assemblage of smectites and chlorites and of primary K-feldspar to muscovite and microcline. Within a closed-system doublet, the composition of the circulated fluid changes only slightly during its repeated passage through the reservoir, as the wall rock essentially undergoes isochemical recrystallization. Even after 30 years of circulation, the calculations show that porosity is reduced by only ∼0.2%, well below the expected fracture porosity induced by stimulation. This result suggests that permeability reduction owing to water–rock interaction is unlikely to jeopardize the long-term operation of deep, granitoid-hosted EGS systems. A peculiarity at Basel is the presence of anhydrite as fracture coatings at ∼5000 m depth. Simulated exposure of the circulating fluid to anhydrite induces a stronger redox disequilibrium in the reservoir, driving dissolution of ferrous minerals and precipitation of ferric smectites, hematite and pyrite. However, even in this scenario the porosity reduction is at most 0.5%, a value which is unproblematic for sustainable fluid circulation through the reservoir.

Translational diffusion of water in compacted clay systems

The translational diffusion of water in compacted clays at a high hydration level has been investigated by quasielastic neutron scattering at a time-of-flight spectrometer FOCUS (SINQ). Four compacted clays with systematic structural differences have been studied: Na-montmorillonite, Na-illite, kaolinite and pyrophyllite. The QENS experiments were performed using two different incident wavelengths in order to access a larger Q range and verify the data analysis. The translational diffusion coefficient for water in Na-montmorillonite and Na-illite are lower than those for bulk water, whereas the preliminary results for kaolinite and pyrophyllite show larger diffusion coefficient.