Human Neutrophil Lipocalin as a Superior Diagnostic Means To Distinguish between Acute Bacterial and Viral Infections

The distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) concentrations in serum or whole blood activated by formyl-methionine-leucine-phenylalanine (fMLP) were shown to distinguish acute infections of bacterial or viral cause with high accuracy. The aim was therefore to compare the clinical performance of HNL with currently used biomarkers. Seven hundred twenty-five subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the study. C-reactive protein (CRP), the expression of CD64 on neutrophils, procalcitonin (PCT), and blood neutrophil counts were measured by established techniques, and HNL concentrations were measured in whole-blood samples after activation with fMLP. All tested biomarkers were elevated in bacterial as opposed to viral infections (P < 0.001). CRP, PCT, and CD64 expression in neutrophils was elevated in viral infections compared to healthy controls (P < 0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the receiver operating characteristic (ROC) curves were >0.85 for all biomarkers, whereas for the distinction between bacterial and viral infections, only HNL concentration in fMLP-activated whole blood showed an area under the ROC curve (AUROC) of >0.90 and superior clinical performance. The clinical performance of HNL in fMLP-activated whole blood was superior to current biomarkers and similar to previous results of HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.     

Dephosphorylation of myo-inositol phosphates in the in vitro intestinal Caco-2 cell model

Plant and microbial phytases present in raw materials can cause a dephosphorylation of phytate (myo-inositol hexakisphosphate) (InsP₆)) during food processing resulting in a broad range of different myo-inositol phosphates such as pentakisphosphate (InsP₅) and tetrakisphosphate (InsP₄) in foods. Here, we investigated whether the human intestinal epithelium is able to dephosphorylate myo-inositol phosphates (InsP₆, InsP₅-, InsP₄-, InsP₃-isomers) using an in vitro model with differentiated human Caco-2 cells cultured on semipermeable inserts. Incubation of InsP₆ and an InsP₅-isomer with cells for 3?h showed no dephosphorylation of both InsPs. Treatment of cells with a mixture of different InsP₄-isomers, however, caused a formation of about 3.5% of an InsP₃-isomer (Ins(1,5,6)P₃) and treatment with a mixture of different InsP₃-isomers caused about 20% formation of InsP₂-isomers, respectively. Thus, human intestinal cells can contribute to the dephosphorylation of myo-inositol phosphates of partly dephosphorylated forms such as InsP₃ and InsP₄.     

Paraoxonase 1 Q192R (PON1-192) polymorphism is associated with reduced lipid peroxidation in R-allele-carrier but not in QQ homozygous elderly subjects on a tomato-rich diet

Summary. Background: The oxidative modification of LDL is considered to play a central role in the pathogenesis of atherosclerosis and coronary heart disease (CHD). Paraoxonase (PON1) protects LDL from oxidation and may therefore retard the developement of atherosclerosis. The PON1–192 polymorphism is associated with diminished PON1 concentrations and an increased risk for CHD in RR-allele subjects. Aim of the study: To investigate the effect of tomato juice consumption on PON1 activity and other parameters related to oxidative stress in healthy elderly subjects. Furthermore, the PON1–192 genotype has been determined in the volunteers in order to see whether possible treatment effects are related to the PON1–192 polymorphism. Methods: Fifty elderly subjects were randomly assigned to control (mineral water) or intervention group (tomato juice). Subjects of the tomato juice group consumed daily 330 mL tomato juice for 8 weeks. Antioxidant status was measured as LDL oxidation, plasma malondialdehyde, ferric reducing ability of plasma (FRAP) and PON1 activity. The PON1–192 polymorphism was determined by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). Plasma carotenoids were analyzed by HPLC. Results: Tomato juice consumption reduced LDL-oxidation and improved antioxidant status in R-allele carriers, but not in the QQ genotype group. PON1 activity increased irrespective of the genotype in both, control and intervention group. Conclusions: The changes in antioxidant status after tomato juice consumption seem to depend on the PON1–192 genotype. Healthy elderly, carrying the R-allele, could specificly reduce their higher cardiovascular risk by changing dietary habits. Received: 9 October 2002, Accepted: 28 October 2002 Correspondence to: Achim Bub     

Soluble adhesion molecules, cytokines and cellular markers in serum in patients with acute infections

The aim of this study was to evaluate the diagnostic capacity of a number of blood components such as soluble adhesion molecules, interleukin-6 (IL-6), myeloperoxidase (MPO) and lysozyme in the distinction of acute bacterial and viral infections. Blood was taken from 115 acutely infected patients at admission before any treatment and in some cases on several consecutive days. 35 of the patients had a definite viral cause for their infection and 66 a bacterial cause. All variables were raised in patients with acute bacterial infections. Soluble vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, lysozyme and MPO were also raised in acute viral infections, but for sE-selectin and MPO less so than in bacterial infections. Evaluation of the diagnostic power showed that for MPO and IL-6 at cut-offs of 1300 microg/l and 100 ng/l, respectively, the positive predictive value was 97% and 100% and the negative predictive value 78% and 76%, respectively, in the classification of acute bacterial infections. In the distinction between viral or bacterial causes of acute infections in otherwise healthy subjects serum measurements of MPO and IL-6 are valuable tools and should be considered as diagnostic aids in the routine setting. The soluble adhesion molecules did not offer any further information in this respect.     

Clinical efficacy and safety of the orally inhaled neuraminidase inhibitor zanamivir in the treatment of influenza: a randomized, double-blind, placebo-controlled European study

OBJECTIVES: To assess the clinical efficacy and safety of orally inhaled zanamivir in the treatment of influenza in a European primary care setting. METHODS: This was a randomized, double-blind, placebo-controlled trial in primary care and hospital clinics in 11 European countries. Patients aged > or = 12 years were recruited within 2 days of onset of typical influenza symptoms and received orally inhaled zanamivir 10 mg via a Diskhaler twice daily for 5 days or matching placebo. Influenza symptoms and temperature were recorded daily for 14 days. The primary endpoint was time to alleviation of clinically significant symptoms of influenza. Other endpoints included symptom severity, use of relief medications, time to return to normal activities, complications and investigator's assessment of symptoms. RESULTS: A total of 356 patients were recruited; 277 (78%) had laboratory-confirmed influenza and 32 (9%) were considered high-risk (i.e. elderly or with underlying medical conditions). Zanamivir significantly reduced the time to alleviation of symptoms versus placebo (median 5 days versus 7.5 days, P<0.001), a 33% reduction in duration of illness. Zanamivir significantly reduced the severity of several symptoms; improvements versus placebo were discernible after approximately 24 h. The proportion of patients who were afebrile after 24 h increased by 46% versus placebo. Similar treatment benefits were observed in the high-risk patients. Zanamivir was well tolerated, with an adverse event profile similar to that of placebo. CONCLUSIONS: Zanamivir is effective in reducing the duration and severity of influenza illness and is well tolerated. Zanamivir should therefore be a clinically valuable intervention in the management of influenza.     

Comparative analysis of two venipuncture learning methods on nursing students

Introduction

Venus cannulation is one of the main nursing actions. For the safety of patients and nurses, this skill is important to be performed in a proper and responsible way. Thus, the need for adequate education on this skill is essential.

Study objective

Comparison between the 4-stage (demonstration, deconstruction, comprehension, performance) learning method and the simplified 2-stage method (deconstruction, performance) on venous cannulation.

Methods

The study took place from November 2011 to March 2012. In total, 117 students of the Nursing Department of Technological Educational Institute of Athens were randomized into two education groups of the 2- (Group A) and 4- (Group B) stage method respectively. Students of both groups were assessed during training and 45 days later for skill retention. For the assessment of all students, a check list with the steps required to venous cannulation was used. The time to complete the process was also assessed.

Results

Group A included 54 students and Group B 50 students. During initial training, the average time to complete the process without any errors was lower for Group A compared to Group B (1.77 ± 0.12 min vs. 2.33 ± 0.13 min, p = 0.006). Regarding the appropriate steps for venous cannulation, Group A made fewer errors compared to Group B (0.95 ± 0.95 vs. 1.38 ± 1.10, p = 0.021). In addition, Group A omitted more steps than Group B (0.29 ± 0.06 vs. 0.11 ± 0.05, p = 0.042). During skill retention assessment, no significant difference was observed in the number of incorrect steps or in the number of omitted steps between groups.

Conclusion

According to our findings, the 4-stage method, is associated with less omitted steps, while the 2-stage method, is associated with less time required to complete the procedure and less errors during performance, at initial stages. However, skill retention does not seem to be associated with the type of the educational methodology.     

Polymer gel water equivalence and relative energy response with emphasis on low photon energy dosimetry in brachytherapy

The water equivalence and stable relative energy response of polymer gel dosimeters are usually taken for granted in the relatively high x-ray energy range of external beam radiotherapy based on qualitative indices such as mass and electron density and effective atomic number. However, these favourable dosimetric characteristics are questionable in the energy range of interest to brachytherapy especially in the case of lower energy photon sources such as 103Pd and 125I that are currently utilized. In this work, six representative polymer gel formulations as well as the most commonly used experimental set-up of a LiF TLD detector-solid water phantom are discussed on the basis of mass attenuation and energy absorption coefficients calculated in the energy range of 10 keV-10 MeV with regard to their water equivalence as a phantom and detector material. The discussion is also supported by Monte Carlo simulation results. It is found that water equivalence of polymer gel dosimeters is sustained for photon energies down to about 60 keV and no corrections are needed for polymer gel dosimetry of 169Yb or 192Ir sources. For 125I and 103Pd sources, however, a correction that is source-distance dependent is required. Appropriate Monte Carlo results show that at the dosimetric reference distance of 1 cm from a source, these corrections are of the order of 3% for 125I and 2% for 103Pd. These have to be compared with corresponding corrections of up to 35% for 125I and 103Pd and up to 15% even for the 169Yb energies for the experimental set-up of the LiF TLD detector-solid water phantom.