Phenytoin toxicity in patients with traumatic brain injury.

BACKGROUND: We observed that in patients with traumatic brain injury (TBI) who did not improve as expected, serum levels of phenytoin were in the toxic range and that their sensorium improved with modification of the dose. This led us to study the usage of phenytoin in patients with TBI. AIMS: To determine the prevalence of phenytoin toxicity in TBI patients and to study the suitability of using ideal body weight (IBW) to guide phenytoin dosing. SETTING AND DESIGN: Neurotrauma unit of a tertiary care centre in India. Prospective data collection from an already established protocol of drug level monitoring. MATERIALS AND METHODS: The study cohort included 100 consecutive adult patients with mild or moderate TBI who were administered phenytoin based on IBW. Trough serum phenytoin and albumin levels were measured on day 4 after administration of the loading dose and actual body weight obtained when it was possible. STATISTICAL ANALYSIS: Chi-square was used for comparing categorical variables, student's t-test for continuous variables and multivariate regression analysis to obtain independent risk factors. RESULTS: Clinical toxicity was observed in 15% of patients and biochemical toxicity in 36%, with a significant association between the two (P < 0.01). Using multivariate analysis, abdominal girth ≤75 cm (P = 0.07), neck circumference ≤34 cm (P = 0.025) and IV dose proportion ≥80% (P = 0.003) were independent risk factors for biochemical toxicity. The plot between actual weight and IBW showed that toxicity occurred when IBW was higher than actual weight. CONCLUSION: The prevalence of biochemical phenytoin toxicity was high, with independent risk factors being a higher proportion of IV administration and overestimation of weight by IBW. Clinical suspicion of phenytoin toxicity was a good predictor of biochemical toxicity.

A comparison of thermal transitions in dip- and spray-assisted layer-by-layer assemblies.

Spray-assisted layer-by-layer (LbL) assembly is far more rapid than conventional dip-assisted assembly methods and has gained widespread interest recently. Even so, it has remained unclear as to how the structure and properties of the resulting LbL film vary with processing method. Here, we compared the thermal properties of poly(ethylene oxide) (PEO)/poly(acrylic acid) (PAA) and PEO/poly(methacrylic acid) (PMAA) hydrogen-bonded LbL assemblies prepared using both dip-assisted and spray-assisted deposition methods. While the surface morphologies of PEO/PAA LbL assemblies were similar, those of PEO/PMAA LbL assemblies were greatly influenced by deposition method. In both PEO/PAA and PEO/PMAA LbL assemblies, glass transition temperatures were not influenced by deposition method, but the transition's breadth was consistently larger for the spray-assisted LbL films. These results indicate that the internal structure of spray-assisted LbL films is slightly more heterogeneous, possibly arising from the shorter time scale of deposition.

Effect of thickness on the thermal properties of hydrogen-bonded LbL assemblies.

Layer-by-layer (LbL) assemblies have attracted much attention for their functional versatility and ease of fabrication. However, characterizing their thermal properties in relation to the film thickness has remained a challenging topic. We have investigated the role of film thickness on the glass transition temperature (T(g)) and coeffecient of thermal expansion for poly(ethylene oxide)/poly(acrylic acid) (PEO/PAA) and PEO/poly(methacrylic acid) (PEO/PMAA) hydrogen-bonded LbL assemblies in both bulk and ultrathin films using modulated differential scanning calorimetry (modulated DSC) and temperature-controlled ellipsometry. In PEO/PAA LbL films, a single, well-defined T(g) was observed regardless of film thickness. The T(g) increased by 9 °C relative to the bulk T(g) as film thickness decreased to 30 nm because of interactions between the film and its substrate. In contrast, PEO/PMAA LbL films show a single glass transition only after a thermal cross-linking step, which results in anhydride bonds between PMAA groups. The T(g), within error, was unaffected by film thickness, but PEO/PMAA LbL films of thicknesses below ~2.7 µm exhibited a small amount of PEO crystallization and phase separation for the thermally cross-linked films. The coefficients of thermal expansion of both types of film increased with decreasing film thickness.

In-plane correlations in a polymer-supported lipid membrane measured by off-specular neutron scattering.

Polymer-supported single lipid bilayers are models to study configurations of cell membranes. We used off-specular neutron scattering to quantify in-plane height-height correlations of interfacial fluctuations of such a lipid bilayer. As temperature decreased from 37 °C to 25 °C, the polymer swells and the polymer-supported lipid membrane deviates from its initially nearly planar structure. A correlation length characteristic of capillary waves changes from 30 µm at 37 °C to 11 µm at 25 °C, while the membrane bending rigidity remains roughly constant in this temperature range.

Surface instabilities in ultrathin, cross-linked poly(N-isopropylacrylamide) coatings.

Near-the-surface instabilities with a cusplike morphology were observed in ultrathin photo-cross-linked poly(N-isopropylacrylamide) coatings upon swelling in water. The characteristic wavelength of the instability was approximately 25 times the dry thickness and scaled linearly with coating thickness between 30 and 1200 nm. Above 1200 nm, slippage of the coating along the confining substrate led to reticulated patterns with a much larger wavelength. To help interpret the origin of the instability, the coatings were also exposed to a solvent slightly worse than water (acetone) and a solvent slightly better than water (isopropanol). In all cases, the characteristic wavelength scaled linearly with respect to the swelling induced by each solvent. Both water and isopropanol produced well-defined cusps or folds in the gel surface, while acetone produced semiordered blisters that grew into one another. The features produced in acetone may be a consequence of swelling being close to the threshold value for the loss of planar stability. Through the use of a first-order linear perturbation of the Flory-Rehner model, it is shown that the emergence of a characteristic wavelength is consistent with an inhomogeneous distribution of solvent that results from diffusion of solvent into a dry coating.

Design and Characterization of a PVLA-PEG-PVLA Thermosensitive and Biodegradable Hydrogel.

A set of poly(δ-valerolactone-co-d,l-lactide)-b-poly(ethylene glycol)-b-poly(δ-valerolactone-co-d,l-lactide) (PVLA-PEG-PVLA) triblock copolymers was synthesized and the solution properties were characterized using rheology, cryo-TEM, cryo-SEM, SANS, and degradation studies. This polymer self-assembles into a low viscosity fluid with flowerlike spherical micelles in water at room temperature and transforms into a wormlike morphology upon heating, accompanied by gelation. At even higher temperatures syneresis is observed. At physiological temperature (37 °C) the hydrogel's average pore size is around 600 nm. The PVLA-PEG-PVLA gel degrades in about 45 days in cell media, making this unique hydrogel a promising candidate for biomedical applications.

Importance of fibrinogen in dilutional coagulopathy after neurosurgical procedures: A descriptive study.

BACKGROUND AND AIMS: The routine management of coagulopathy during surgery involves assessing haemoglobin, prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelets. Correction of these parameters involves administration of blood, fresh frozen plasma and platelet concentrates. The study was aimed at identifying the most common coagulation abnormality during neurosurgical procedures and the treatment of dilutional coagulopathy with blood components. METHODS: During 2 years period, all adult patients undergoing neurosurgical procedures who were transfused two or more units of red cells were prospectively evaluated for the presence of a coagulopathy. PT, aPTT, platelet count and fibrinogen levels were estimated before starting a component therapy. RESULTS: After assessing PT, aPTT, platelet count and fibrinogen levels following two or more blood transfusions, thirty patients were found to have at least one abnormal parameter that required administration of a blood product. The most common abnormality was a low fibrinogen level, seen in 26 patients; this was the only abnormality in three patients. No patient was found to have an abnormal PT or aPTT without either the fibrinogen concentration or platelet count or both being low. CONCLUSION: Low fibrinogen concentration was the most common coagulation abnormality found after blood transfusions for neurosurgical procedures.

Temperature-triggered shape-transformations in layer-by-layer microtubes.

One-dimensional layer-by-layer (LbL) nano- and microtubes have been extensively studied for energy and biomedical applications. Here, we report a temperature-triggered transformation in shape for LbL microtubes consisting of poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA). PAH/PAA microtubes were assembled onto porous sacrificial templates. Released microtubes transform to closed ellipsoids upon heating in water. On the other hand, unreleased microtubes (remaining within the template) exhibit a completely different behavior in which periodic perforations appear, suggestive of Rayleigh instabilities. In both cases, the transformations occurred near and above the glass transition temperature (Tg) of the hydrated PAH/PAA LbL assembly, suggesting that the transformation in shape is tied to the thermal properties of the LbL assembly.

Thermal transitions in dry and hydrated layer-by-layer assemblies exhibiting linear and exponential growth.

Layer-by-layer (LbL) assemblies are remarkable materials, known for their tunable mechanical, optical, and surface properties in nanoscale films. However, questions related to their thermal properties still remain unclear. Here, the thermal properties of a model LbL assembly of strong polyelectrolytes, poly(diallyldimethylammonium chloride)/poly(styrene sulfonate) (PDAC/PSS), assembled from solutions of varying ionic strength (0-1.25 M NaCl) are investigated using quartz crystal microbalance with dissipation (QCM-D) and modulated differential scanning calorimetry. Hydrated exponentially growing films (assembled from 0.25 to 1.25 M NaCl) exhibited distinct thermal transitions akin to a glass transition at 49-56 °C; linearly growing films (assembled without added salt) did not exhibit a transition in the temperature range investigated and were glassy. Results support the idea that exponentially growing films have greater segmental mobility than that of linearly growing films. On the other hand, all dry LbL assemblies investigated were glassy at room temperature and did not exhibit a T(g) up to 250 °C, independent of ionic strength. For the first time, thermal transitions such as T(g) values can be measured for LbL assemblies using QCM-D by monitoring fluctuations in changes in dissipation, allowing us to probe the film's internal structure as a function of film depth.

Model lipid membranes on a tunable polymer cushion.

A hydrated, surface-tethered polymer network capable of fivefold change in thickness over a 25-37 degrees C temperature range has been demonstrated via neutron reflectivity and fluorescence microscopy to be a novel support for single lipid bilayers in a liquid environment. As the polymer swells from 170 to 900 A, it promotes both in- and out-of-plane fluctuations of the supported membrane. The cushioned bilayer proved to be very robust, remaining structurally intact for 16 days and many temperature cycles. The promotion of membrane fluctuations offers far-reaching applications for this system as a surrogate biomembrane.