An improved laboratory protocol to assess subarachnoid haemorrhage in patients with negative cranial CT scan.

BACKGROUND: The laboratory analysis of cerebrospinal fluid (CSF) plays a key role in considering subarachnoid haemorrhage (SAH) in patients with clinical suspicion, but negative CT scan. Although the determination of the CSF bilirubin concentration generally provides high sensitivity, it was recently shown that specificity and positive predictive value are unacceptably low, limiting its use as a diagnostic tool. METHODS: We intended to design and evaluate an improved laboratory protocol, which fulfills the requirement of better specificity without losing sensitivity. We present a procedure in which a "bili-excess" concentration is determined, which is the surplus CSF bilirubin measured after subtraction of an estimated upper limit for the individual patient. The latter is calculated from [bilirubin](serum), [albumin](serum) and [albumin](CSF), taking into account the propagation of analytical errors in the individual analyses. We investigated the applicability of direct absorption vs. derivative spectroscopy, thereby addressing the influence of various calibration methods. We evaluated our procedure in 92 CSF samples drawn from patients with (n=37) and without (n=55) clinical suspicion of SAH. RESULTS: In our study population, we show that specificity increases from 0.83 (95% CI, 0.74-0.91) to 1.00 (95% CI, 0.96-1.00) using the bili-excess concept, with an established upper limit for bili-excess of 0.11 micromol/L instead of the recommended use of an "uncorrected" CSF bilirubin upper limit of 0.20 micromol/L. Sensitivity in both cases is 1.00 (95% CI, 0.66-1.00). We demonstrate the merit of allowing for analytical imprecision in the bili-excess concept. CONCLUSIONS: We provide a quantitative procedure to explore the likelihood of (CT-negative) SAH independent of the absolute CSF bilirubin concentration by considering the "bili-excess" concentration per individual, using derivative spectroscopy to determine CSF bilirubin. This procedure led to an increase in specificity to 1.00 (95% CI, 0.96-1.00) in our study population.

Do we measure bilirubin correctly anno 2005?

We observed 30% discrepancy between liquid chemistry and dry chemistry analysers for the determination of total bilirubin in human adult serum samples, which were consistent with a 20% overestimation and 10% underestimation relative to a Jendrassik-Grof reference method, respectively. In contrast, standard reference material SRM916, which was recently recommended as being the most suitable material for attaining interlaboratory agreement, shows very good agreement on both types of analysers, as well as close to 100% recovery with respect to the reference method. We show that the liquid vs. dry bilirubin discrepancies seem to originate in the presence of either conjugated or delta-bilirubin. Our observations make it clear that good interlaboratory (or inter-analyser) agreement between bilirubin reference materials does not guarantee the same for bilirubin concentrations in human serum samples.

A quantitative appraisal of interference by icodextrin metabolites in point-of-care glucose analyses.

An important number of patients dependent on renal dialysis prefer peritoneal dialysis to hemodialysis. In the case of peritoneal dialysis, the glucose polymer icodextrin is frequently added to the dialysis fluid as an osmotic agent, since this polymer is able to maintain an osmotic gradient across the peritoneal membrane longer than monomeric glucose, leading to a prolonged effective ultrafiltration time. It was previously shown that icodextrin is partly able to enter the blood via the lymphatic system, where hydrolysis to glucose oligomers such as maltose and maltotriose occurs. The presence of these oligomers in the blood appears to cause significant overestimations of the glucose values in several point-of-care (POC) glucose analyzers, with potentially dramatic consequences. This effect has been investigated for a series of POC glucose analyzers, both by analyzing the blood of peritoneal dialysis patients and by an in vitro investigation of the quantitative effects of maltose and maltotriose. In particular, POC analyzers utilizing the bacterially produced enzyme glucose dehydrogenase seem to lack glucose specificity.

Optical and redox properties of a series of 3,4-ethylenedioxythiophene oligomers.

The optical and redox properties of a series of 3,4-ethylenedioxythiophene oligomers (EDOTn, n=1-4) and their beta,beta'-unsubstituted analogues (Tn, n=1-4) are described. Both series are end capped with phenyl groups to prevent irreversible alpha-coupling reactions during oxidative doping. Absorption and fluorescence spectra of both series reveal a significantly higher degree of intrachain conformational order in the EDOTn oligomers. Oxidation potentials (E(PA1) and E(PA2)) determined by cyclic voltammetry reveal that those of EDOTn are significantly lower than the corresponding Tn oligomers as a consequence of the electron-donating 3,4-ethylenedioxy substitution. Linear fits of E(PA1) and E(PA2) versus the reciprocal number of double bonds reveal significantly steeper slopes for the EDOTn than for the Tn oligomers. This could indicate a more effective conjugation for the EDOTn series, confirmed by the fact that coalescence of E(PA1) and E(PA2) is reached already at relatively short chain lengths ( approximately 5 EDOT units) in contrast to the Tn series (>10 thiophene units). The stepwise chemical oxidation of the EDOTn and Tn oligomers in solution was carried out to obtain radical cations and dications. The energies of the optical transitions of the radical cations and dications as determined by UV/Vis/NIR spectroscopy were similar for the two series. These spectroscopic observations are consistent with quantum-chemical calculations performed on the singly charged molecules. Cooling solutions containing T2.+, T3.+, EDOT2.+, and EDOT3.+ revealed the reversible formation of dimers, albeit with a somewhat different tendency, expressed in the values for the dimerization enthalpy.