Chance of aneurysm in patients suspected of SAH who have a 'negative' CT scan but a 'positive' lumbar puncture.

In patients with sudden severe headache and a negative computed tomography (CT) scan, a lumbar puncture (LP) is performed to rule in or out a subarachnoid haemorrhage (SAH), but this procedure is under debate. In a hospital-based series of 30 patients with sudden headache, a negative CT scan but a positive LP (defined as detection of bilirubin >0.05 at wavelength 458 nm), we studied the chance of harbouring an aneurysm and the clinical outcome. Aneurysms were found in none of both patients who presented within 3 days, in 8 of the 18 (44%) who presented within 4-7 days and in 5 of the 10 (50%) who presented within 8-14 days. Of the 13 patients with an aneurysm, 3 (23%) had poor outcome. In patients who present late after sudden headache, the yield in terms of aneurysms is high in those who have a positive lumbar puncture. In patients with an aneurysm as cause of the positive lumbar puncture, outcome is in the same range as in SAH patients admitted in good clinical condition.

Prediction of fetal lung immaturity using gestational age, patient characteristics and fetal lung maturity tests: a probabilistic approach.

OBJECTIVES: The lecithin/sphingomyelin (L/S) ratio and the lamellar body count (LBC) can be used to predict respiratory distress syndrome (RDS). DESIGN: We performed a retrospective cohort study among consecutive women who underwent amniotic fluid sampling for the assessment of fetal lung maturity. Logistic regression was used to construct models for the prediction of RDS in three gestational age categories, with models based on clinical characteristics only, clinical characteristics and the LBC, and on clinical characteristics and L/S ratio. RESULTS: When amniotic fluid was collected <30 weeks, the specificity of the LBC was 30% and the sensitivity 100%. Addition of the L/S ratio increased the specifity to 60%, for a sensitivity of 100%. When amniocentesis was performed between 30 and 33 weeks, addition of the L/S ratio only marginally improved the performance of the LBC. CONCLUSIONS: At a gestational age <30 weeks, the L/S ratio has additional value over the LBC. Above 30 weeks of gestation, single use of the LBC seems sufficient.

Serum paraoxonase-I activity is unaffected by short-term administration of simvastatin, bezafibrate, and their combination in type 2 diabetes mellitus.

BACKGROUND: The high-density lipoprotein (HDL)-associated anti-oxidative and anti-inflammatory enzyme, paraoxonase-I, has been found previously to be lower in type 2 diabetes mellitus. We studied whether statin and fibrate treatment, alone and in combination, affect serum paraoxonase-I activity in conjunction with changes in HDL cholesterol in diabetic patients. SUBJECTS AND METHODS: A placebo-controlled crossover study was carried out in 14 type 2 diabetic patients to test the effect of 8 weeks of active treatment with simvastatin (40 mg daily), bezafibrate (400 mg daily), and their combination on serum paraoxonase-I activity, measured as its activity towards arylesterase and paraoxon. Serum paraoxonase-I activity was also compared between these diabetic patients and 49 non-diabetic control subjects. RESULTS: Serum arylesterase activity was lower in type 2 diabetic patients compared to control subjects (P < 0.001), but the difference in paraoxonase activity was not significant (P = 0.22). Neither arylesterase (P = 0.24) nor paraoxonase activity (P = 0.37) was increased in response to treatment, despite higher HDL cholesterol and apolipoprotein A-I during combination therapy (P < 0.05 for both). CONCLUSION: Short-term administration of simvastatin and bezafibrate, even when combined, is ineffective in raising serum paraoxonase-I activity in type 2 diabetes.

Lung maturation in small for gestational age fetuses from pregnancies complicated by placental insufficiency or maternal hypertension.

BACKGROUND: Clinical studies suggest that respiratory outcome of infants born preterm may be influenced by placental insufficiency and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. If so, one could expect to see differences in lung maturation indices (lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC)) in the amniotic fluid. The present study investigates lung maturation indices of preterm small for gestational age (SGA) fetuses with or without abnormal Doppler ultrasound examination and with or without maternal hypertension/HELLP syndrome. STUDY DESIGN: Retrospective cohort study of 76 neonates born in our center between 1997 and 2003 with gestational age (GA) <34 weeks, birth weight

Genetic and environmental determinants of the PON-1 phenotype.

BACKGROUND: Paraoxonase (PON-1) is a high-density lipoprotein (HDL)-associated enzyme that may protect against cardiovascular disease (CVD), because it hydrolyses oxidized phospholipids of low-density lipoprotein (LDL) and therefore prevents the detrimental effects on the arterial wall. The current report describes the determinants of PON-1 bioavailability and activity. MATERIALS AND METHODS: This is the largest (n = 1527) cross-sectional evaluation performed on PON-1 genotypes (Q192R, T-107C and L55M) and environmental determinants to PON-1 catalytic activity and bioavailability in serum of postmenopausal women. PON-1 catalytic activity and PON-1 bioavailability were measured, in vitro, with a paraoxon hydrolysis assay and a phenylacetate hydrolysis assay, respectively. RESULTS: The major determinant of paraoxon hydrolytic activity is the Q192R genotype, but there was also a relation with the C-107T and L55M genotype, HDL levels and alcohol consumption. Phenylacetate hydrolytic activity was most strongly affected by the C-107T genotype followed by the L55M genotype, HDL levels, alcohol consumption and smoking. CONCLUSIONS: PON-1 Q192R, C-107T and L55M genotype, alcohol consumption, smoking and HDL levels are determinants of serum PON-1 phenotype. The contributions of the genetic markers to the PON-1 phenotype are stronger than the contributions of the lifestyle determinants.

Evaluation of nephelometry for albumin measurement in serum and cerebrospinal fluid: experiences with an indwelling subarachnoidal catheter system for repetitive cerebrospinal fluid collection in horses.

The measurement of albumin concentrations in cerebrospinal fluid (CSF) and serum for albumin quotient (AQ) calculations in normal horses was performed by 2 methods: 1) total protein measurement, followed by electrophoresis of the samples to obtain an albumin percentage; and 2) albumin immunoprecipitation quantitated by nephelometry. The results of both methods correlated well, and nephelometry was chosen to determine the albumin concentrations in CSF samples obtained from an indwelling subarachnoidal catheter for daily sampling. Because the use of an indwelling catheter to collect repetitive CSF samples is a novel technique, routine cytological CSF analysis was performed along with daily clinical evaluation to ascertain the well-being of the horses. The catheters were placed in 2 horses for periods of 14 and 17 days. One horse exhibited pleocytosis on cytological evaluation of CSF on 2 occasions for a 1-2-day duration; however, the AQ showed a significant increase on only 1 occasion. The other horse had a normal cell count in CSF but showed 2 sudden changes in the AQ value; however, these values remained within the 95% confidence interval for AQ in horses. Albumin quotient values of the second horse were consistently below the lower range of the confidence interval. Results from this study indicate that nephelometry can be used for albumin determination in serum and CSF samples from horses. Furthermore, an indwelling subarachnoidal catheter system can provide serial CSF samples in horses, thus obviating the need for repetitive centesis for serial CSF sampling.

The effect of statin therapy on plasma high-density lipoprotein cholesterol levels is modified by paraoxonase-1 in patients with familial hypercholesterolaemia.

OBJECTIVES: Statins reduce low-density lipoprotein cholesterol (LDL-C) and can raise high-density lipoprotein cholesterol (HDL-C). HDL-bound paraoxonase-1 (PON1) is associated with variations in plasma HDL-C, and may, therefore, contribute to changes of HDL-C during statin therapy. DESIGN: The effects of baseline PON1 status to HDL-C changes because of statin therapy were investigated. PON1 status was determined with (i) PON1 -107C>T and 192Q>R genotype, (ii) PON1 levels and (iii) PON1 paraoxonase, diazoxonase and arylesterase activity. SETTING: Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. SUBJECTS: A total of 134 familial hypercholesterolaemia (FH) patients undergoing atorvastatin or simvastatin therapy. RESULTS: PON1 levels and activities significantly modified the HDL-C increment (P=0.002 for PON1 levels and arylesterase activity and P=0.001 for diazoxonase activity). The effects were even more evident amongst subgroup classifications based on PON1 status and baseline HDL-C concentrations: the HDL-C increment was more pronounced in subgroups of -107CT/TT or 192QR/RR genotype combined with low baseline HDL-C (+13.9%, P<0.001, respectively+15.4%, P<0.001). In contrast, the -107CC or 192QQ genotype in combination with high baseline HDL-C, did not show a significant increase of HDL-C. CONCLUSIONS: PON1 status in conjunction with baseline HDL-C levels predicts HDL-C increment during statin therapy in FH patients.

Visual inspection versus spectrophotometry in detecting bilirubin in cerebrospinal fluid.

OBJECTIVES: To compare the diagnostic accuracy of visual inspection and spectrophotometry for identifying the presence of bilirubin in the cerebrospinal fluid (CSF). METHODS: Clinicians and students assessed CSF specimens with seven degrees of extinction between 0.00 and 0.09 at 450-460 nm as "yellow," "doubtful," or "colourless" after random presentation under standard conditions. The assessments were compared with spectrophotometry, with 0.05 being taken as the cut off level for the presence of bilirubin. Results were compared between the two groups and explored by means of receiver operating characteristic (ROC) curves. RESULTS: All 51 clinicians and 50 of 51 students scored the tubes with extinction of 0.06 or higher as "yellow" or "doubtful." Tubes without any bilirubin were scored as "yellow" by three of the students only. The ROC curves confirmed that the diagnostic properties of the visual inspection versus spectrophotometry were slightly better for the clinicians than for the students. CONCLUSIONS: If CSF is considered colourless, the extinction of bilirubin is too low to be compatible with a diagnosis of recent subarachnoid haemorrhage. If CSF is not considered colourless, spectrophotometry should be carried out to determine the level of extinction of bilirubin.

Influenza and pneumococcal vaccination as a model to assess C-reactive protein response to mild inflammation.

This study was set up to examine whether an influenza vaccine or an influenza vaccine in combination with pneumococcal vaccine can be used as a model to study responses to mild stimulation of the inflammatory system. In this study, 19 subjects received the influenza vaccine, 20 subjects the combination of influenza and pneumococcal vaccine. CRP and prothrombin fragment 1 and 2 (F1+2) were measured at baseline, and two times after vaccination. Influenza vaccination increased CRP by 0.20 mg/L, and influenza in combination with pneumococcal vaccine increased CRP by 0.60 mg/L. F1+2 increased 0.15 nmol/L after the combined vaccination; an increase in response to the influenza vaccination was not statistically significant. Our findings show that the influenza vaccine alone as well as the combination of the influenza and pneumococcal vaccine increases CRP-levels with a peak 2 days after vaccination.

Effect of inflammatory attacks in the classical type hyper-IgD syndrome on immunoglobulin D, cholesterol and parameters of the acute phase response.

BACKGROUND: Classical type hyper-immunoglobulin D (IgD) syndrome (HIDS) is an hereditary auto-inflammatory disorder, characterized by recurrent episodes of fever, lymphadenopathy, abdominal distress and a high serum concentration of IgD. It is caused by mevalonate kinase deficiency. OBJECTIVE: To further characterize the acute phase response during fever attacks in HIDS in order to improve diagnosis. SUBJECTS: Twenty-two mevalonate kinase-deficient HIDS patients. METHODS: Blood samples were drawn during and in between febrile attacks, and concentrations ofC-reactive protein (CRP), ferritin, procalcitonin, pentraxin 3, IgD and cholesterol in several lipoprotein fractions were determined. RESULTS: The marked acute phase response at the time of a fever attack in classical type HIDS is reflected by a rise in CRP accompanied by a moderate but statistically significant rise in procalcitonin and pentraxin 3. In only two of 22 patients, procalcitonin concentration rose above 2 ng mL(-1) during fever attack, compatible with the noninfectious nature of these attacks. Ferritin does not reach the high concentrations found in adult-onset Still's disease. Despite the defect in mevalonate kinase, a component of cholesterol metabolism, serum cholesterol did not change during attacks. IgD concentration is elevated regardless of disease activity, although there is appreciable variation during life. Its role in HIDS remains unclear. CONCLUSION: The combination of high CRP concentration plus procalcitonin concentration <2 ng mL(-1) in a symptomatic HIDS patient might indicate a febrile attack without (bacterial) infection; this observation warrants further investigation for its usefulness as a marker in clinical practice.

Increased high molecular weight fibrinogen in pre-eclampsia.

INTRODUCTION: The major coagulation protein fibrinogen (Fg) is a heterogeneous protein with three main fractions: high molecular weight fibrinogen (HMW-Fg), low molecular weight fibrinogen (LMW-Fg) and low molecular weight' fibrinogen. The clottability of high molecular weight fibrinogen is highest as compared to the other fractions. Pre-eclampsia is associated with a state of hypercoagulability, and with an increase of fibrinogen concentration. The aim of the present study was to examine if the increased total fibrinogen plasma concentration in patients with pre-eclampsia is associated with a change in distribution of the main fibrinogen fractions. MATERIAL AND METHODS: Plasma was collected from 14 patients with pre-eclampsia and from 14 healthy pregnant matched controls. Total fibrinogen concentrations were determined according to Clauss. The percentage high molecular weight fibrinogen was assessed by SDS-electrophoresis and densitometry after isolation of fibrinogen by precipitation. The study groups were compared by the Mann-Whitney U-test. RESULTS: The median (range) total fibrinogen concentration in the pre-eclampsia group was 5.04 (3.25-6.51) g/l and in the control group 4.19 (3.61-5.38) g/l (p<0.05). The median (range) percentage high molecular weight fibrinogen was 76.5 (69.6-84.0)% and 73.0 (69.0-78.9)% in the pre-eclampsia and control group, respectively (p<0.05). CONCLUSIONS: In pre-eclampsia, the concentration of total fibrinogen is increased and the percentage high molecular weight fibrinogen is also slightly higher than in normal pregnancy. These results may be a reflection of the exaggerated inflammatory response, and subsequent endothelial activation, which are currently believed to be the key pathophysiological mechanisms in pre-eclampsia.

Changes of plasma lipoprotein(a) during and after normal pregnancy in Caucasians.

OBJECTIVE: Elevated plasma concentrations of lipoprotein(a) are associated with an increased risk for development of atherosclerosis. High lipoprotein(a) concentrations may also be associated with pregnancy-induced hypertension and pre-eclampsia, but reference data on the course of lipoprotein(a) during uneventful pregnancies are limited and questionable. METHODS: We studied plasma lipoprotein(a) concentrations in 19 healthy nulliparous Caucasian women during and after uncomplicated pregnancy. Blood was sampled every 4 weeks during pregnancy from 9 weeks onwards, during labor and at 2-4 weeks and 3-5 months after delivery. An apolipoprotein(a) (apo(a)) isoform-independent enzyme-linked immunosorbent assay (ELISA) was used to measure lipoprotein(a). Multilevel analysis was used to describe the data. RESULTS: Lipoprotein(a) increased until 35 weeks, subsequently decreased slightly until delivery, and fell to values below early pregnancy concentrations thereafter. The curve is defined by the formula lipoprotein(a) (mg/l) = exp [4.789 + (0.05215 x GA) + (-0.0007371 x GA2)] where GA = gestational age in weeks. CONCLUSIONS: We constructed a curve for plasma lipoprotein(a) which may serve as the standard reference for changes in pregnancy. Its formula is helpful in predicting changes of gestational age-dependent changes of lipoprotein(a) in normal pregnancy.

The effect of clinical characteristics on the lecithin/sphingomyelin ratio and lamellar body count: a cross-sectional study.

OBJECTIVES: To study the changes in the lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC) during pregnancy and to study the effect of clinical characteristics on these measurements. METHODS: We reviewed in retrospect the amniotic fluid samples for the assessment of fetal lung maturity of consecutive women between January 1996 and December 2000. We evaluated the effect of antenatal administration of glucocorticoids, the presence of diabetes, fetal growth restriction and the amount of amniotic fluid on the L/S ratio and LBC. We then constructed normal curves, by relating the L/S ratio and LBC to gestational age in the cases without respiratory distress syndrome (RDS). Data from the literature were added to these curves. RESULTS: From the 334 included women, 64 infants (19%) developed RDS. The LBC was lower in women with polyhydramnios (p = 0.04), and similar in women with oligohydramnios. Administration of glucocorticoids, the presence of maternal diabetes or fetal growth restriction did not affect the L/S ratio or the LBC. The median L/S ratio in cases without RDS showed a constant increase from a gestational age of 28 weeks onwards. The median LBC increased slowly between a gestational age of 28 weeks and 34 weeks, to increase more steeply thereafter. CONCLUSIONS: The amount of amniotic fluid affects the LBC, but not the L/S ratio. Since the L/S ratio and the LBC increase with gestation, differences in gestational age should be taken into account in the interpretation of these fetal lung maturity tests.

Iron does not bind to the Apo-B protein of low-density lipoprotein.

BACKGROUND: Epidemiological and experimental evidence suggests that (nontransferrin-bound) iron plays an important role in atherogenesis by catalysing peroxidation of low-density lipoprotein (LDL). However, the mechanism of the interaction of iron and LDL is unclear. Iron has to be in the closest vicinity of LDL in order to catalyse the formation of the short-lived hydroxyl. In this study we investigated whether iron can bind to LDL in order to facilitate LDL peroxidation. METHODS: LDL and [(59)Fe]ferric citrate were incubated at 37 degrees C and pH 7.4 for 30 min. Unbound [(59)Fe]ferric citrate was separated from LDL using a Sephadex G25-M column. Activity of [59Fe]ferric citrate was measured in the collected fractions. A control experiment was performed using albumin instead of LDL. RESULTS AND CONCLUSION: No binding was observed between iron, as a low molecular weight Fe(III) complex, and LDL. As a control albumin was able to bind iron, it seems evident that interaction of iron with LDL will involve other iron complexes.

[Procalcitonin concentrations in the diagnosis of acute inflammatory reactions]. / Procalcitonineconcentraties als diagnosticum bij acute ontstekingsreacties.

Procalcitonin is a calcitonin prohormone. During systemic inflammatory response it has the characteristics of an acute-phase protein. However, plasma levels rise more rapidly than those of the parameter (i.e. C-reactive protein) currently used in clinical practice to assess an acute-phase response. The procalcitonin assay is easy to perform and results can be available within a short period of time. This makes procalcitonin a valuable addition to the current diagnostic work-up for acutely ill patients. Procalcitonin can be used as a marker of inflammation, to differentiate serious bacterial infections from other generalised inflammatory diseases, to differentiate bacterial from viral infections, to differentiate infection from disease activity in patients with autoimmune diseases, to differentiate infection from rejection in transplant patients, and as a prognostic marker in critically ill patients. Procalcitonin may prove to be a valuable adjunct in diagnosing and treating patients with a variety of inflammatory disorders.