Epidemiological and clinical aspects of the Guillain-Barre Syndrome

The Guillain-Barre syndrome (GBS) is an acute immune-mediated disorder of the peripheral nerves. The essential features are a rapidly progressive, more or less symmetrical weakness of the limbs and decreased or absent tendon reflexes. The weakness reaches its nadir (maximum severity) by definition within four weeks, but it is usually seen within two weeks. In 20-30% of the patients, weakness is so severe that artificial ventilation is needed. People of all age, gender or race can be affected by this polyneuropathy. The first symptoms of GBS are often preceded by an infection. Seventy percent of the patients report influenzalike symptoms, a respiratory infection or a gastro-enteritis within the three weeks prior to the onset of the disease. The first description of what is now called the Guillain-Barre syndrome, was given by J.B.O. Landry in 1859 1 . The summation of clinical characteristics was extended by typical findings in the cerebrospinal fluid as described by G. Guillain, JA Barre and A Strohl in 1916 2 • As research progressed, many studies reported on the clinical diversity of GBS. As a consequence, the concept of GBS shifted from a single clinical entity to a disease with heterogeneity in presentation, course and outcome. Nowadays GBS is considered to be a post-infectious immune-mediated acute polyneuropathy with a heterogeneous symptomatology

IVIG Treatment and Prognosis in Guillain–Barré Syndrome

Introduction Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyneuropathy that often leads to severe weakness. Intravenous immunoglobulin (IVIG) is a proven effective treatment for GBS (class 1 evidence). However, about 25% of patients need artificial ventilation and 20% are still unable to walk unaided after 6 months. Important clinical factors associated with poor outcome are age, presence of preceding diarrhea and the severity of disability in the early course of disease. These clinical factors were combined in a clinical prognostic scoring scale, the Erasmus GBS Outcome Scale (EGOS). Materials and Methods GBS patients being unable to walk unaided are currently treated with a standard single IVIg dose (0.4 g/kg bodyweight for 5 days). A recent retrospective study in 174 GBS patients enrolled in one of our randomized controlled clinical trials showed that patients with a minor increase of serum IgG level after standard single IVIg dose recovered significantly slower. Additionally, fewer patients reached the ability to walk unaided at six months after correction for the known clinical prognostic factors (multivariate analysis; P<0.022). Discussion It is yet unknown why some GBS patients only have a minor increase after standard IVIg treatment. By using the EGOS it is possible to select GBS patients with a poor prognosis. These patients potentially may benefit from a second IVIg dose. Conclusion A standard dose of IVIG is not sufficiently effective in many GBS patients. Whether these patients might benefit from a second IVIg dose needs further investigation

A simple approach to polymer mixture miscibility

Polymeric mixtures are important materials, but the control and understanding of mixing behaviour poses problems. The original Flory–Huggins theoretical approach, using a lattice model to compute the statistical thermodynamics, provides the basic understanding of the thermodynamic processes involved but is deficient in describing most real systems, and has little or no predictive capability. We have developed an approach using a lattice integral equation theory, and in this paper we demonstrate that this not only describes well the literature data on polymer mixtures but allows new insights into the behaviour of polymers and their mixtures. The characteristic parameters obtained by fitting the data have been successfully shown to be transferable from one dataset to another, to be able to correctly predict behaviour outside the experimental range of the original data and to allow meaningful comparisons to be made between different polymer mixtures

Fractionation of polydisperse systems: multi-phase coexistence

The width of the distribution of species in a polydisperse system is employed in a small-variable expansion, to obtain a well-controlled and compact scheme by which to calculate phase equilibria in multi-phase systems. General and universal relations are derived, which determine the partitioning of the fluid components among the phases. The analysis applies to mixtures of arbitrarily many slightly-polydisperse components. An explicit solution is approximated for hard spheres.Comment: 4 pages, 1 figur

Predicting phase equilibria in polydisperse systems

Many materials containing colloids or polymers are polydisperse: They comprise particles with properties (such as particle diameter, charge, or polymer chain length) that depend continuously on one or several parameters. This review focusses on the theoretical prediction of phase equilibria in polydisperse systems; the presence of an effectively infinite number of distinguishable particle species makes this a highly nontrivial task. I first describe qualitatively some of the novel features of polydisperse phase behaviour, and outline a theoretical framework within which they can be explored. Current techniques for predicting polydisperse phase equilibria are then reviewed. I also discuss applications to some simple model systems including homopolymers and random copolymers, spherical colloids and colloid-polymer mixtures, and liquid crystals formed from rod- and plate-like colloidal particles; the results surveyed give an idea of the rich phenomenology of polydisperse phase behaviour. Extensions to the study of polydispersity effects on interfacial behaviour and phase separation kinetics are outlined briefly.Comment: 48 pages, invited topical review for Journal of Physics: Condensed Matter; uses Institute of Physics style file iopart.cls (included

Bright light increases alertness and not cortisol in healthy men:A forced desynchrony study under dim and bright light (I)

Light-induced improvements in alertness are more prominent during nighttime than during the day, suggesting that alerting effects of light may depend on internal clock time or wake duration. Relative contributions of both factors can be quantified using a forced desynchrony (FD) designs. FD designs have only been conducted under dim light conditions (<10 lux) since light above this amount can induce non-uniform phase progression of the circadian pacemaker (also called relative coordination). This complicates the mathematical separation of circadian clock phase from homeostatic sleep pressure effects. Here we investigate alerting effects of light in a novel 4 × 18 h FD protocol (5 h sleep, 13 h wake) under dim (6 lux) and bright light (1300 lux) conditions. Hourly saliva samples (melatonin and cortisol assessment) and 2-hourly test sessions were used to assess effects of bright light on subjective and objective alertness (electroencephalography and performance). Results reveal (1) stable free-running cortisol rhythms with uniform phase progression under both light conditions, suggesting that FD designs can be conducted under bright light conditions (1300 lux), (2) subjective alerting effects of light depend on elapsed time awake but not circadian clock phase, while (3) light consistently improves objective alertness independent of time awake or circadian clock phase. Reconstructing the daily time course by combining circadian clock phase and wake duration effects indicates that performance is improved during daytime, while subjective alertness remains unchanged. This suggests that high-intensity indoor lighting during the regular day might be beneficial for mental performance, even though this may not be perceived as such

Bright light during wakefulness improves sleep quality in healthy men:A forced desynchrony study under dim and bright light (III)

Under real-life conditions, increased light exposure during wakefulness seems associated with improved sleep quality, quantified as reduced time awake during bed time, increased time spent in non-rapid eye movement (NREM) sleep, or increased power of the electroencephalogram delta band (0.5-4 Hz). The causality of these important relationships and their dependency on circadian phase and/or time awake has not been studied in depth. To disentangle possible circadian and homeostatic interactions, we employed a forced desynchrony protocol under dim light (6 lux) and under bright light (1300 lux) during wakefulness. Our protocol consisted of a fast cycling sleep-wake schedule (13 h wakefulness-5 h sleep; 4 cycles), followed by 3 h recovery sleep in a within-subject cross-over design. Individuals (8 men) were equipped with 10 polysomnography electrodes. Subjective sleep quality was measured immediately after wakening with a questionnaire. Results indicated that circadian variation in delta power was only detected under dim light. Circadian variation in time in rapid eye movement (REM) sleep and wakefulness were uninfluenced by light. Prior light exposure increased accumulation of delta power and time in NREM sleep, while it decreased wakefulness, especially during the circadian wake phase (biological day). Subjective sleep quality scores showed that participants rated their sleep quality better after bright light exposure while sleeping when the circadian system promoted wakefulness. These results suggest that high environmental light intensity either increases sleep pressure buildup during wakefulness or prevents the occurrence of micro-sleep, leading to improved quality of subsequent sleep

Comparative study of different methods for the prediction of drug-polymer solubility

YesIn this study, a comparison of different methods to predict drug−polymer solubility was carried out on binary systems consisting of five model drugs (paracetamol, chloramphenicol, celecoxib, indomethacin, and felodipine) and polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios. The drug−polymer solubility at 25 °C was predicted using the Flory−Huggins model, from data obtained at elevated temperature using thermal analysis methods based on the recrystallization of a supersaturated amorphous solid dispersion and two variations of the melting point depression method. These predictions were compared with the solubility in the low molecular weight liquid analogues of the PVP/VA copolymer (N-vinylpyrrolidone and vinyl acetate). The predicted solubilities at 25 °C varied considerably depending on the method used. However, the three thermal analysis methods ranked the predicted solubilities in the same order, except for the felodipine−PVP system. Furthermore, the magnitude of the predicted solubilities from the recrystallization method and melting point depression method correlated well with the estimates based on the solubility in the liquid analogues, which suggests that this method can be used as an initial screening tool if a liquid analogue is available. The learnings of this important comparative study provided general guidance for the selection of the most suitable method(s) for the screening of drug−polymer solubility.The Irish Research Council and Eli Lilly S.A. through an Irish Research Council Enterprise Partnership Scholarship for C.M.B., in part by The Royal Society in the form of Industrial Fellowship awarded to G.A., and in part by a research grant from Science Foundation Ireland (SFI) under Grant Number SFI/12/RC/2275 (for A.M.H., L.T., K.P., and A.K.)