Risk factors for prolonged duration of mechanical ventilation in acute traumatic tetraplegic patients--a retrospective cohort study.

PURPOSE: Respiratory complications constitute an important determinant of length of stay in tetraplegic patients. In a population of tetraplegic patients, we investigated the factors involved in the duration of mechanical ventilation (MV) and whether the duration of MV was associated with the long-term neurologic status. MATERIAL AND METHODS: In a retrospective study in 3 intensive care units (ICUs) (January 2001 to December 2009), consecutive patients (≥ 18 years) hospitalized for acute (≤ 24 hours) traumatic tetraplegia were included in the study. Patients with severe brain injury or who died in the first 48 hours were excluded. The primary outcome was the duration of MV. The secondary outcomes were the American Spinal Injury Association (ASIA) motor score on ICU discharge and at 1 year. RESULTS: A total of 164 consecutive adult patients with tetraplegia were analyzed. Median (interquartile range) ASIA motor scores were 15 (6-26) on admission, 22 (9-40) on ICU discharge (n = 145 survivors), and 37 (10-80) at 1 year (n = 52 complete follow-up). The median duration of MV was 11 (2-26) days. In multivariate analysis, MV duration increased with pneumonia (P < .0001), atelectasis (P = .0042), and tracheotomy (P < .0001). In exploratory analysis, an increased duration of MV was the only factor associated in multivariate analysis with a low ASIA motor score on ICU discharge (P = .0201) and at 1 year (P = .0003). CONCLUSIONS: Prevention of pneumonia and atelectasis is critical for the reduction of MV in tetraplegic patients. Prolonged MV was independently associated with poor neurologic status.

Conformational studies on five octasaccharides isolated from chondroitin sulfate using NMR spectroscopy and molecular modeling.

Chondroitin sulfate proteoglycans (CS-PG) are involved in the regulation of the central nervous system in vertebrates due to their presence on cell surfaces and in the extracellular matrix of tissues. The CS moieties are built up from repeating -4)GlcA(beta1-3)GalNAc(beta1- disaccharide units, partly O-sulfated at different positions. The presence of the disulfated disaccharide D-unit, GlcA2S(beta1-3)GalNAc6S, in the CS moiety of the proteoglycan DSD-1-PG/phosphacan, correlates with neurite outgrowth promotion. The binding of monoclonal antibody (mAb) 473HD to DSD-1-PG, reducing neuronal stimulation, is inhibited by shark cartilage CS-D. CS-D is also recognized by two other mAbs, MO-225 and CS-56. Conformational studies were performed using NMR spectroscopy and molecular modeling on five octasaccharides isolated from shark cartilage CS-D. These octasaccharides present different binding properties toward the three mAbs. The combination of the experimental and theoretical approaches revealed that the sulfate group at position 2 of GlcA in disaccharide D and the presence of an exocyclic negative tail in disaccharides C [GlcA(beta1-3)GalNAc6S] and DeltaC [Delta4,5HexA(alpha1-3)GalNAc6S] are important for antibody recognition.

Structure and dynamics of the conserved protein GPI anchor core inserted into detergent micelles.

A suitable approach which combines nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations have been used to study the structure and the dynamics of the glycosylphosphatidylinositol (GPI) anchor Manalphal-2Manalpha1-6Manalphal -4GlcNalpha1-6myo-inositol-1-OPO(3)-sn-1,2-dimyristoylglycerol (1) incorporated into dodecylphosphatidylcholine (DPC) micelles. The results have been compared to those previously obtained for the products obtainable from (1) after phospholipase cleavage, in aqueous solution. Relaxation and diffusion NMR experiments were used to establish the formation of stable aggregates and the insertion of (1) into the micelles. MD calculations were performed including explicit water, sodium and chloride ions and using the Particle Mesh Ewald approach for the evaluation of the electrostatic energy term. The MD predicted three dimensional structure and dynamics were substantiated by nuclear overhauser effect (NOE) measurements and relaxation data. The pseudopentasaccharide structure, which was not affected by incorporation of (1) into the micelle, showed a complex dynamic behaviour with a faster relative motion at the terminal mannopyranose unit and decreased mobility close to the micelle. This motion may be better described as an oscillation relative to the membrane rather than a folding event.

The heparin-Ca(2+) interaction: the influence of the O-sulfation pattern on binding.

The specific binding of Ca(2+) to synthetic hexasaccharide models of modified heparin has been investigated by NMR and molecular modeling and compared with previous results on a model of regular heparin. These two models represent the regular region of heparin lacking one type of O-sulfate group, either at C-6 of glucosamine or at C-2 of iduronate. The NMR experiments show different responses to the presence of Ca(2+). In the case of the compound lacking O-sulfate groups at C-2, the results are indicative of specific binding similar to that observed for the regular heparin, while the model lacking sulfate groups in position 6 interacts more weakly with Ca(2+). In order to understand the basis of this difference, a molecular modeling study based on a rigid body docking approach of the interaction of these carbohydrates with Ca(2+) and Na(+) was performed. We have found that the results are strongly dependent on the starting orientation of the lateral side chains of the charged groups of the carbohydrate, and that the best agreement with the experimental results is obtained when the starting conformations are taken from previous simulations in the presence of Ca(2+).