bluuebunny/crossref_metadata_2025 huggingface dataset:
An Algebra for Queueing Networks with Time-Varying Service and Its Application to the Analysis of Integrated Service Networks
Authors: Agrawal Rajeev , Baccelli François , Rajan Rajendran
Published: August 2004

We introduce a network model that allows us to capture the time-varying service delivered to a traffic stream due to the presence of random perturbations (e.g., cross-traffic in a communication network). We first present the model for a single network element and then describe how such elements may be interconnected using the operations of fork and join. Such networks may be seen as a generalization of stochastic event graphs and of the class of fork-join networks. The departure processes in such a network satisfy a system of equations along with the exogenous arrival processes and the service processes of the various network elements. This system can be seen as a general time-varying linear system in the (min, plus) semi-field. We obtain an explicit representation of the departure process in terms of the exogenous arrival processes and the service processes. Sufficient conditions are derived for this system to have a unique solution. We also study liveness and absence of explosion in this class of networks. Under appropriate stationarity and ergodicity assumptions, we establish stability theorems for such networks. To this end we first obtain a rate result for the departure process in terms of the rates of the exogenous arrival process and the throughput of a saturated system. We then use this result to show that in a network with a single exogenous arrival, all queue lengths are finite with probability one if the arrival rate is less than the throughput of the saturated system, and to give a representation of the queue-length process. This class of networks allows for a detailed description of controlled sessions in integrated service networks. We also show that it contains several earlier discrete event models of the literature pertaining to stochastic Petri nets, service curves, and fork-join networks and show how the present model unifies them in a single algebraic structure. This structure is that of a semi-ring of functions of two real variables, where the addition is the pointwise minimum and the multiplication a generalization of inf-convolution.
Population Pharmacokinetics I: Background, Concepts, and Models
Authors: Ette Ene I , Williams Paul J
Published: August 2004

OBJECTIVE

To present and emphasize the background, foundations, utility, and conceptual underlying theory of the population pharmacokinetic (PPK) approach with an examination of the advantages when compared with other approaches of pharmacokinetic modeling.

DATA SOURCES

Information on PPK was retrieved from a MEDLINE search (1979—June 2002) of literature and a bibliographic review of review articles and books.

STUDY SELECTION AND DATA EXTRACTION

All articles identified from data sources were evaluated and relevant information was included in this review.

DATA SYNTHESIS

PPK plays a pivotal role in developing dosing strategies for direct patient care and in drug development. PPK is valuable because it targets the patient group that will eventually receive the drug of interest, quantitates pharmacokinetic variability at several levels, and seeks to explain those sources of variability.

CONCLUSIONS

PPK models have great utility and the applications are many. They are very different from single-subject pharmacokinetic models and therefore require different approaches to model development.
Physical and Chemical Stability of Palonosetron HCl in 4 Infusion Solutions
Authors: Trissel Lawrence A , Xu Quanyun A
Published: August 2004

BACKGROUND

Palonosetron HCl is a selective 5-HT3 receptor antagonist used for the prevention of chemotherapy-induced nausea and vomiting. Palonosetron HCl may be diluted in an infusion solution for administraton. Consequently, stability information is needed for palonosetron HCl admixed in common infusion solutions.

OBJECTIVE

To evaluate the physical and chemical stability of palonosetron HCl in concentrations of 5 and 30 μg/mL in dextrose 5% injection, NaCl 0.9% injection, dextrose 5% in NaCl 0.45% injection, and dextrose 5% in lactated Ringer's injection.

METHODS

Triplicate test samples of palonosetron HCl at each concentration in each diluent were tested. Samples were stored and evaluated at appropriate intervals for up to 48 hours at room temperature (~23 °C) and 14 days under refrigeration (4 °C). Physical stability was assessed using turbidimetric and particulate measurement, as well as visual inspection. Chemical stability was assessed by HPLC.

RESULTS

All of the admixtures were initially clear and colorless when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially and remained low throughout the study. The drug concentration was unchanged in any of the samples at either temperature throughout the study.

CONCLUSIONS

Palonosetron HCl is physically and chemically stable in all 4 common infusion solutions for at least 48 hours at room temperature and 14 days under refrigeration.
Impact of Pharmacists' Interventions on the Pediatric Discharge Medication Process
Authors: Voirol Pierre , Kayser Steven R , Chang Chi Y , Chang Q Laura , Youmans Sharon L
Published: August 2004

BACKGROUND

To our knowledge, as of August 19, 2004, the impact of pharmacists' interventions on pediatric patients and their caregivers' ability to obtain discharge medications from community pharmacies in a timely fashion has not been described.

OBJECTIVE

To evaluate the impact of pharmacists' interventions on patients' likelihood of obtaining medications within 24 hours of hospital discharge.

METHODS

Patients meeting study criteria were randomized to an intervention or control group. The intervention was a proactive program of discharge planning by the pharmacy team. All study patients received a follow-up telephone interview to assess the amount of time needed to obtain medications and caregivers' knowledge of how to administer medications. A multivariate linear regression was conducted to assess the association between variables such as insurance, place of residence, number of prescribed medications, and the probability to obtain medications within 24 hours of hospital discharge.

RESULTS

The final analysis included 81 control patients and 91 intervention patients. After controlling for a number of factors, the intervention group was able to have obtained medications within 24 hours more often than the control group (84% vs 69%; p = 0.027). Caregivers' knowledge of how to correctly administer medications did not differ between the 2 groups.

CONCLUSIONS

Our results suggest that the coordinated efforts of pharmacists' interventions during the discharge process may have a positive impact. Our observations may be used to establish criteria for identifying patients at risk for problems with obtaining medications at discharge.
Sirolimus-Associated Hepatotoxicity in Liver Transplantation
Authors: Neff Guy W , Ruiz Phillip , Madariaga Juan R , Nishida Seigo , Montalbano Marzia , Meyer Doug , Levi David M , Tzakis Andreas G , O'Brien Christopher B
Published: August 2004

BACKGROUND

Sirolimus is an immunosuppressant that exerts anti-rejection activity by inhibiting T-cell activity and is used to treat chronic rejection and calcineurin-related nephrotoxicity. Unlike tacrolimus and cyclosporine, it has no effect on calcineurin activity in liver transplant recipients.

OBJECTIVE

To report correlates of survival outcomes in a series of patients with putative sirolimus-related hepatotoxicity after liver transplant.

METHODS

We retrospectively reviewed the medical records of patients who underwent a liver transplant for chronic hepatitis C virus (HCV) and who received sirolimus immunosuppressive therapy between November 2000 and November 2003. Extracted data included sirolimus serum concentrations, frequency of sirolimus-related adverse effects, drug-related clinical hepatitis, and survival outcomes.

RESULTS

Ten patients were found to have been treated with sirolimus for either renal insufficiency (n = 6) or chronic rejection (n = 4). Six patients had liver biopsies, while the remaining 4 patients were clinically diagnosed with rejection. Two of the 6 patients demonstrated changes consistent with sinusoidal congestion and one with eosinophilia, consistent with an allergic drug reaction. HCV viral load increased slightly, from 600 000 to 700 000 IU/mL. Mean baseline transaminase levels were 45 IU/L for aspartate aminotransferase and 50 IU/L for alanine aminotransferase, with peak levels of 210 and 180 IU/L, respectively. The time to transaminase increase was a mean of 21 days when sirolimus was added, with resolution within 27 days (mean) after its discontinuation. No changes were evident in antiviral therapy. Combination sirolimus and tacrolimus concentrations were maintained at >10 ng/mL; average monotherapy with sirolimus was 12 ng/mL, and average time on therapy was 25 weeks.

CONCLUSIONS

Sirolimus-related hepatotoxicity is an important complication after liver transplant. Immediate recognition is critical to avoid confusion with other causes of abnormal serum aminotransferases after liver transplant, and discontinuation of the drug may be required.
Matrix metalloproteinases, inflammation and atherosclerosis: therapeutic perspectives
Authors: Beaudeux Jean-Louis , Giral Philippe , Bruckert Eric , Foglietti Marie-José , Chapman M. John
Published: August 2004

Matrix metalloproteinases (MMPs), also called matrixins, are proteinases that participate in extracellular matrix remodelling and degradation. Under normal physiological conditions, the activities of MMPs are precisely regulated at the level of transcription, of activation of the pro-MMP precursor zymogens and of inhibition by endogenous inhibitors (tissue inhibitors of metalloproteinases; TIMPs). Alteration in the regulation of MMP activity is implicated in diseases such as cancer, fibrosis, arthritis and atherosclerosis. The pathological effects of MMPs and TIMPs in cardiovascular diseases involve vascular remodelling, atherosclerotic plaque instability and left ventricular remodelling after myocardial infarction. Since excessive tissue remodelling and increased matrix metalloproteinase activity have been demonstrated during atherosclerotic lesion progression (including plaque disruption), MMPs represent a potential target for therapeutic intervention aimed at modification of vascular pathology by restoring the physiological balance between MMPs and TIMPs. This review describes the members of the MMP and TIMP families and discusses the structure, function and regulation of MMP activity; finally, pharmacological approaches to MMP inhibition are highlighted.
Concomitant isolation of protein C inhibitor and unnicked β2-glycoprotein I
Authors: Čučnik Saša , Križaj Igor , Rozman Blaž , Kveder Tanja , Božić Borut
Published: August 2004

β
Decreased expression of the insulin-like growth factor-I-binding protein-1 (IGFBP-1) phosphoisoform in pre-eclamptic Wharton's jelly and its role in the regulation of collagen biosynthesis
Authors: Bańkowski Edward , Sobolewski Krzysztof , Palka Jerzy , Jaworski Stefan
Published: August 2004

Insulin-like growth factor-I (IGF-I) is known as an important stimulator of collagen and glycosaminoglycans (GAGs) biosynthesis in tissues. IGF-I activity is under control of IGF-I-binding proteins (IGFBPs) with different IGF-I-binding affinity. IGFBP-1 is known as an inhibitor of IGF-dependent functions. Some IGFBPs (e.g., IGFBP-1) may undergo phosphorylation that dramatically increases IGFBP affinity for IGF. Wharton's jelly represents a reservoir of IGF-I and its binding proteins (BPs). Pre-eclampsia, the most common, pregnancy-associated pathological syndrome, contributes to a significant decrease in IGF-I and IGFBP-1 content in Wharton's jelly, although it does not affect collagen content in this tissue. In the present study we show that control Wharton's jelly contains phosphorylated forms of IGFBP-1 that are dramatically dephosphorylated during pre-eclampsia. A dramatic decrease in IGF-I binding to immunoprecipitated IGFBP-1 from pre-eclamptic Wharton's jelly compared to the control was observed. Western immunoblot analysis with anti-phosphothreonine antibodies for immunoprecipitated IGFBP-1 from control and pre-eclamptic Wharton's jelly revealed that both tissues contain phosphorylated forms of IGFBP-1. However, a distinct decrease in the expression of phosphorylated IGFBP-1 from pre-eclamptic Wharton's jelly was observed. The functional significance of the phenomenon was found in cultured fibroblasts treated with IGFBP isolated from Wharton's jelly extracts. A significant decrease in collagen biosynthesis was found in the cells treated with IGFBP of control Wharton's jelly, while in the presence of IGFBP from pre-eclamptic Wharton's jelly, the rate of collagen biosynthesis was similar to that in the control cells. The result was corroborated by data showing increase in expression of IGF-I receptor and phosphorylated MAP kinases (ERK1 and ERK2) in fibroblasts cultured in the presence of IGFBP from pre-eclamptic Wharton's jelly, compared to control. The data suggest that the decrease in phosphorylated IGFBP-1 in pre-eclamptic Wharton's jelly may decrease IGF-I-binding affinity for IGF and increase the bioavailability of IGF-I for receptor interaction. This mechanism may facilitate IGF-I-dependent stimulation of fibroblasts to produce extracellular matrix (ECM) components even at a low IGF-I tissue level. Therefore, IGFBP-1 phosphoisoforms in Wharton's jelly may play an important role in the regulation of IGF-I-dependent functions during pre-eclampsia.
Immunoglobulin G Fcγ receptor expression on polymorphonuclear cells in bronchoalveolar lavage fluid of HIV-infected and HIV-seronegative patients with bacterial pneumonia
Authors: Armbruster Christine , Krugluger Walter , Huber Monika , Kriwanek Stephan
Published: August 2004

This study was designed to test the hypothesis that impaired neutrophil function might contribute to the development of bacterial pneumonia in patients with HIV-infection. Numbers of inflammatory cells and immunoglobulin G Fcγ receptor (IgG FcγR) I, II, III levels were investigated in bronchoalveolar lavage (BAL) fluid of HIV-seronegative and HIV-infected patients with bacterial pneumonia. The 99 patients were classified into three groups: I: HIV-seronegative and pneumonia (n=40); II: HIV-infected and pneumonia (n=19); III: HIV-seronegative with other pulmonary diseases than pneumonia (n=40). The results of groups I and II, II and III, and I and III were compared. The percentage of alveolar macrophages was significantly lower (group II vs. III: p=0.005, group I vs. III: p=0.001), that of neutrophils increased significantly in patients with pneumonia (group II vs. III: p=0.02, group I vs. III: p=0.01). Lymphocytes differed only between groups I and III (p=0.04). Although only the expression of FcγRI was significantly higher in HIV-seronegative pneumonia patients compared to those without pneumonia (p=0.01), the mean expression of all three receptors was lower in the HIV-infected group, with that of FcγRI approaching statistical significance.

This report provides first evidence that altered FcγR expression on BAL neutrophils might contribute to the increased susceptibility of HIV-infected patients to bacterial pneumonia.
Testing and validating a homogeneous immunometric assay for interference
Authors: Bjerner Johan , Olsen Kari Hauge , Børmer Ole P. , Nustad Kjell
Published: August 2004

We analyzed 95 sera, demonstrating interference in a previous study, with the Kryptor homogeneous time-resolved fluorescence resonance energy transfer carcinoembryonic antigen (CEA) immunoassay (Brahms AG, Berlin, Germany). Only one serum differed, i.e., 6.0 μg/l for Kryptor vs. 13.3 μg/l for a microtiter plate in-house immunofluorometric assay (IFMA), using both aggregated mouse immunoglobulins as blocker and capture monoclonal antibody (Mab) F(ab′)

Kryptor-CEA assay results thus agreed with our inhouse CEA assay results, showing no interference. As the Kryptor-CEA assay antibodies were sensitive to interference and the Kryptor-CEA assay buffer did not reduce interference as efficiently as our in-house assay buffer, the Kryptor-CEA assay format was crucial for the absence of interference.
Linearity evaluation of analytical methods that count particles
Authors: Magari Robert T. , Rodriguez Leslie
Published: August 2004

Linearity evaluation of an analytical method is important for both manufacturers of diagnostic devices and laboratory users. Some of the statistical assumptions for estimation and testing in linear regression are violated in analytical methods that count particles per unit of volume or/and time, leading to potential erroneous evaluation of linearity. The objective of this paper is to provide an approach for evaluating linearity in these cases. The number of counts for each concentration level has a Poisson probability distribution that is linear, second-, or higher-order polynomial function of the concentration. Maximum likelihood approach is used to estimate the parameters of the models. Deviance of a particular model and the likelihood ratio test are used to test for linearity. An evaluation of linearity of an analytical method in multiple experiments is also described. No particular changes to the standard testing protocols and data collections are necessary. There are several statistical software packages that can perform the calculations. Formulas and SAS codes presented in this article can also assist in estimation and statistical testing.
Phage-displayed recombinant single-chain antibody fragments with high affinity for cholesteryl ester transfer protein (CETP): cDNA cloning, characterization and CETP quantification
Authors: Ritsch Andreas , Ebenbichler Christoph , Naschberger Elisabeth , Schgoer Wilfried , Stanzl Ursula , Dietrich Hermann , Heinrich Peter C. , Saito Kazunori , Patsch Josef R.
Published: August 2004

Cholesteryl ester transfer protein (CETP) greatly affects the metabolism of all lipoprotein classes including low-density lipoprotein (LDL) and high-density lipoprotein (HDL), bothknown to constitute powerful risk factors for coronary artery disease (CAD). We now report the successful first cloning and characterization of single-chain antibody fragments specific for CETP. A recombinant phage display library was generated using spleen mRNA isolated from BALB/c mice that had been immunized with highly purified CETP. Screening of the library yielded two single-chain antibody fragments with high affinity for CETP, termed 1CL8 and 1CL10, displaying respective K
Stem cell factor and macrophage-colony stimulating factor in patients with pancreatic cancer
Authors: Mroczko Barbara , Szmitkowski Maciej , Wereszczynska-Siemiatkowska Urszula , GrazynaJurkowska Grazyna
Published: August 2004

Stem cell factor (SCF)and macrophage-colony stimulating factor (M-CSF)have assumed an increasing importance in cancer biology. In the present study we investigated the serum levels of these cytokines in pancreatic cancer patients in relation to controls and to patients with benign lesions of the pancreas (chronic pancreatitis group). The classical tumor markers, such as carcinoembryonic antigen (CEA)and carbohydrate antigen 19–9 (CA 19–9)were also tested. We compared the serum levels of cytokines with tumor stage. We also defined the receiver-operating characteristics (ROC)curve for cytokines and classical tumor markers. The cytokines were measured in 47 patients with pancreatic cancer, in 27 patients with chronic pancreatitis and in 35 healthy subjects. SCF and M-CSF were determined using enzyme-linked immunosorbent assay (ELISA). CEA and CA 19–9 were measured by microparticle enzyme immunoassay. There were significant differences in the levels of circulating SCF, M-CSF, CEA and CA 19–9 in the pancreatic cancer patients compared to the control group, but only the serum levels of M-CSF, CEA and CA 19–9 were significantly higher in pancreatic cancer patients compared to the pancreatitis group. The levels of cytokines and tumor markers were higher in patients with a more advanced tumor stage. The M-CSF serum levels correlated positively with the tested tumor markers. The M-CSF area under the ROC curve was higher than the SCF area. These results suggest that M-CSF is a better candidate for a pancreatic cancer tumor marker than SCF.
Modulation of plasma fibrinogen levels in acute-phase response after hepatectomy
Authors: Giovannini Ivo , Chiarla Carlo , Giuliante Felice , Vellone Maria , Nuzzo Gennaro
Published: August 2004

In acute-phase response, the use of amino acids is redirected to supporting the synthesis of proteins for host defence and tissue repair. Fibrinogen is one of these proteins, and its plasma levels commonly increase in acute-phase conditions. After hepatectomy, this pattern may be modified by the variable impact of postoperative liver dysfunction. Our study was performed to specifically assess and quantify this aspect. Data were collected prospectively on 82 hepatectomized patients; 62 recovered normally, 20 had major complications (most commonly sepsis). Plasma fibrinogen and a large series of complementary variables were determined preoperatively and at postoperative days 1, 3 and 7 in all patients and until recovery, or death in those with complications. Multiple regression analysis showed that postoperative changes in fibrinogen (δFIB, μmol/l) were simultaneously related to the number of resected liver segments (NSEG), total bilirubin (BIL, μmol/l), aspartate aminotransferase (AST, U/l, n.v. 5–45), albumin (ALB, g/l), prothrombin activity (PA, % of standard reference), age (AGE, years) and basal preoperative fibrinogen (PFIB, μmol/l): δFIB=−0.51 (NSEG)−0.71 (Log
Expression of activation molecules in neutrophils, monocytes and lymphocytes from patients with unstable angina treated with stent implantation
Authors: Sánchez-Margalet Víctor , Cubero José M. , Martín-Romero Consuelo , Cubero José , Cruz-Fernández José M. , Goberna Raimundo
Published: August 2004

Coronary angioplasty is known to mediate an inflammatory response. Recently, we have characterized the transient systemic inflammatory response after coronary stent implantation in patients with unstable angina by measuring different soluble protein markers. In the present study we have characterized the expression of various cellular activation markers in neutrophils, monocytes and lymphocytes from the same group of patients. Peripheral blood samples were taken before and 24 h, 48 h and 7 days after successful coronary stenting in 58 patients. Cell surface markers (CD11b/CD18 and CD38) were analyzed by flow cytometry to determine the activation of neutrophils, monocytes and T lymphocytes. We found that coronary angioplasty with stent implantation produces an increase in the cell surface expression of CD11b/CD18 in neutrophils and CD38 in monocytes, following a similar time-course with a peak after 24 h, returning to basal levels after 48 h and a second peak after 7 days. However, T lymphocytes were not found to be activated. These results suggest that coronary stent implantation induces a different pattern inducing soluble and cellular inflammation markers, and therefore, they should be taken into account in patients undergoing stent implantation to study clinical correlations.
Acid ribonuclease and alkaline ribonuclease isoenzymes in plasma of patients with decreased glomerular filtration rate
Authors: Naskalski Jerzy , Anyszek Tomasz , Surdacka Ewa , Hoyer Bernadetta , Sulowicz Wladyslaw
Published: August 2004

Removal of low molecular weight proteins from plasma by kidneys depends on glomerular filtration rate (GFR), protein-glomerular membrane electric charge, steric interactions and a number of functionally active nephrons present in the kidneys. There is a well documented relationship between the concentration of low molecular weight proteins in plasma and GFR value in patients with impaired renal function. Accumulation of low molecular weight proteins in plasma along with a decrease in GFR value may in the long run enhance formation of protein tissue deposits known as various forms of amyloidosis. In this paper we present studies on plasma concentrations of acid leukocyte-type ribonuclease (RNase) and alkaline pancreatic-type RNase and GFR value in 54 patients with renal failure. RNase isoenzymes' activities were assayed by measuring their enzyme activities manifested as ability to decompose yeast RNA and assay of digestion products' concentration by spectrophotometry. The studies show that decreasing filtration rate produces an increase in serum activities of both acid and alkaline RNases, which is proportional to the logarithm of GFR value. However, the increase rate vs. GFR value is by four times higher for acid RNase then for alkaline RNase. Acid RNase in human plasma is mostly of leukocytic origin and differs from pancreatic-type alkaline RNase, which is of pancreatic origin. The obtained results may suggest that leukocyte originating proteins essentially contribute to low molecular weight protein accumulation in plasma of patients with chronic renal insufficiency.
Significance of consecutive international normalized ratio (INR) outcomes using statistical control rules in long-term anticoagulated patients. Optimization of laboratory monitoring and interpretation of borderline measurements
Authors: Introcaso Giovanni , Gesu Giampietro
Published: August 2004

Analysis of serial measurements is needed to elaborate observations in all fields of medical research. In the present study, retrospective data of anticoagulated patients were used to calculate a mean of observations and control limits, X±1σ and X±2σ (mean±standard deviation). During 18 months of coagulation monitoring, 45 patients without major oral anticoagulant therapy complications, with more international normalized ratio (INR) determinations in the therapeutic range and with a normal distribution of INR values according to the Kurtosis coefficient, were selected. The cumulative distribution functions allowed us to obtain critical limits of INR with a cumulative probability (p). Control limits, calculated for a therapeutic control chart, indicated through different control rules, 1S
Elevated plasma total homocysteine in centenarians
Authors: Malaguarnera Mariano , Pistone Giovanni , Motta Massimo , Vinci Ernesto , Oreste Giovanni , Avellone Gino , Musumeci Salvatore
Published: August 2004

Homocysteine (Hcy) is a sulfur-containing metabolite of methionine and is an emerging independent risk factor for atherosclerosis. Previous studies have shown that age, gender, renal function and folic acid intake are the main factors influencing total plasma Hcy levels in humans. A unique approach to the science of human longevity is the natural model of centenarians. The objective of this study was to verify whether the previously determined risk factors for atherosclerosis and atherosclerosis-related diseases change with age and, finally, to establish the vitamin nutritional status role.

We studied 54 centenarians (14 males and 40 females) aged between 100–107 years (mean age 102.6±1.8 years) living in Sicily (Italy), recruited via the Registry Office, and compared them with three control groups composed of subjects with different age ranges. Total plasma Hcy, folate, vitamin B

It seems that centenarians are protected by some mechanism (maybe genetic) that allows them a long survival despite the high value of homocysteinemia. On the other hand, it can by hypothesized that good vitamin intake is essential to live over 100 years.
New methodology of influential point detection in regression model building for the prediction of metabolic clearance rate of glucose
Authors: Meloun Milan , Hill Martin , Militký Jiří , Vrbíková Jana , Stanická Sona , Škrha Jan
Published: August 2004

Identifying outliers and high-leverage points is a fundamental step in the least-squares regression model building process. The examination of data quality involves the detection of influential points, outliers and high-leverages, which cause many problems in regression analysis. On the basis of a statistical analysis of the residuals (classical, normalized, standardized, jackknife, predicted and recursive) and diagonal elements of a projection matrix, diagnostic plots for influential points indication are formed. The identification of outliers and high leverage points are combined with graphs for the identification of influence type based on the likelihood distance. The powerful procedure for the computation of influential points characteristics written in S-Plus is demonstrated on the model predicting the metabolic clearance rate of glucose (MCRg) that represents the ratio of the amount of glucose supplied to maintain blood glucose levels during the euglycemic clamp and the blood glucose concentration from common laboratory and anthropometric indices. MCRg reflects insulin sensitivity filtering-off the effect of blood glucose. The prediction of clamp parameters should enable us to avoid the demanding clamp examination, which is connected with a higher load and risk for patients.
Intra-laboratory analytical variability of biochemical markers of fibrosis (Fibrotest) and activity (Actitest) and reference ranges in healthy blood donors
Authors: Imbert-Bismut Françoise , Messous Djamila , Thibaut Vincent , Myers Rob B. , Piton Annie , Thabut Dominique , Devers Laure , Hainque Bernard , Mercadier Anne , Poynard Thierry
Published: August 2004

Combinations of tests comprising α
The glutathione S-transferase polymorphisms in a control population and in Alzheimer's disease patients
Authors: Žuntar Irena , Kalanj-Bognar Svjetlana , Topic Elizabeta , Petlevski Roberta , Štefanović Mario , Demarin Vida
Published: August 2004

In this study, we investigated the role of glutathione S-transferase P1 (GSTP1) polymorphisms in the pathogenesis of Alzheimer's disease (AD). We genotyped the GSTP1 polymorphisms in exon 5 (A313G) and exon 6 (C341T) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 56 Croatian patients with AD and 231 controls. Distributions and frequencies of GSTP1 genetic variants were not statistically different between AD patients and healthy controls. Higher frequencies of the mutant genotypes were observed in AD patients (13% for both A313G and C341T) when compared with control subjects (7% for A313G and 8% for C341T), but association of GSTP1 GG (OR 2.057, 95% CI 0.796–5.315, p=0.094) and TT (OR 1.691, 95% CI 0.669–4.270, p=0.514) genotypes with an increased risk of AD was not confirmed by statistical analysis. The frequencies of
Long-distance mountain biking does not disturb the measurement of total, free or complexed prostate-specific antigen in healthy men
Authors: Herrmann Markus , Scharhag Jürgen , Sand-Hill Marga , Kindermann Wilfried , Herrmann Wolfgang
Published: August 2004

Purpose: Mechanical manipulation of the prostate is a generally accepted interfering factor for the measurement of prostate-specific antigen (PSA). However, only few studies have focused on common daily mechanical manipulations, such as bicycle riding. Furthermore, physical exercise is also supposed to modulate PSA serum concentration. Long-distance mountain biking is an excellent model to study the combined effect of mechanical prostate manipulation by bicycle riding and strenuous endurance exercise on total, free and complexed PSA (tPSA, fPSA, cPSA). Materials and methods: We investigated tPSA, fPSA and cPSA in 42 healthy male cyclists (mean age 35±6 years) before and after a 120 km off-road mountain bike race. Blood sampling was done before, 15 min and 3 h after the race. Results: Mean race time was 342±65 min. All athletes had normal serum levels of tPSA, fPSA or cPSA. None of these parameters was modified by the race. Conclusions: In healthy men the measurement of tPSA, fPSA and cPSA is not disturbed by preceding long distance mountain biking or endurance exercise. Based on the present data, there is no evidence for a recommendation to limit bicycle riding or physical activity before the measurement of tPSA, fPSA or cPSA.
Automated flagging influences the inconsistency and bias of band cell and atypical lymphocyte morphological differentials
Authors: Meer Wim van der , Scott Colin Stephen , Keijzer MarinusH. de
Published: August 2004

This study evaluated inter- and intra-observer variabilities of band cell and atypical lymphocyte differentials and the influence of instrument flagging information on resulting microscopic differentials. Five stained slides with a range of band cell counts and five with variable numbers of atypical lymphocytes were sent for morphological review by 30 technicians. No supplementary full blood cell count information was provided. Two months later, the same slides were sent, together with their corresponding analyzer reports comprising the full blood cell count, automated differentials and flags, to the same technicians. The first and second appraisals of band cells and variant lymphocytes both showed poor levels of inter-observer consistency. Observed values for all slides were very wide and suggested a high inherent predisposition to erroneous reporting practices. Analysis of category trends showed that analyzer left shift or immature granulocytes flags had no influence on observer band cell assessments as downward vs. upward category revisions were evenly balanced. The findings for atypical lymphocytes were, however, somewhat different. Two slides with no flags both showed balanced category revisions, whereas two of the three slides with atypical lymphocyte flags showed clear evidence of upward category revision. The third slide with an atypical lymphocyte flag did not show any overall category trend, but six of the seven observers who in the first examination recorded atypical lymphocyte estimates of ≤30% revised their estimates upward when the slides were examined the second time. These results suggest that morphologist access to an analyzer report and flagging information is unlikely to affect the “randomness” of band cell determinations but it may induce observer bias in variant lymphocyte estimates.
Extracellular concentration of homocysteine in human cell lines is influenced by specific inhibitors of cyst(e)ine transport
Authors: Hultberg Björn
Published: August 2004

Despite the growing evidence that plasma homocysteine is a cardiovascular risk factor, the mechanism behind the vascular injuries is still unknown. Studies of the cellular uptake systems for homocysteine are scarce, but membrane transporters of cyst(e)ine seem to be involved. In the present study the cellular uptake of extracellular homocysteine in HeLa and hepatoma cell lines is investigated by using several different transport inhibitors for cellular uptake of cyst(e)ine. It is shown that systems A and X
Impurities from polypropylene microcentrifuge tubes as a potential source of interference in simultaneous analysis of multiple lipid-soluble antioxidants by HPLC with electrochemical detection
Authors: Yen Hsiu-Chuan , Hsu Yi-Tzu
Published: August 2004

High-performance liquid chromatography (HPLC) with electrochemical detection was used to analyze lipidsoluble antioxidants and micronutrients in plasma. Small amounts of plasma samples are often extracted in polypropylene (PP) microcentrifuge tubes before HPLC analysis due to its convenience. We therefore investigated the effect of impurities released from different PP tubes during extraction on the electrochemical detection of retinol, lutein, α-tocopherol, γ-tocopherol, retinyl palmitate, β-carotene and total coenzyme Q
Cerebrospinal fluid tau and Aβ42 concentrations in healthy subjects: delineation of reference intervals and their limitations
Authors: Burkhard Pierre R. , Fournier Roxane , Mermillod Bernadette , Krause Karl-Heinz , Bouras Constantin , Irminger Irmgard
Published: August 2004

Many limitations and conflicting results have cast serious doubts on the validity of cerebrospinal fluid tau and Aβ42 levels for the biological diagnosis of Alzheimer's disease, particularly extreme variations of the reference limits found by unrelated groups as a consequence of different reference populations used. In this study, we addressed the issue of defining reference limits for cerebrospinal fluid tau and Aβ42 in healthy adult individuals. One hundred and five neurologically intact subjects were enrolled according to strict inclusion criteria, 10 of them with autopsy confirmation of brain integrity. All cerebrospinal fluid samples were similarly and optimally processed as were the dosage methods used and the statistical analyses performed. A robust correlation with age was demonstrated for Aβ42 but not for tau. For tau, we found that an upper cut-off value of 443 ng/l allowed 95% of the subjects to be correctly classified as normal. For Aβ42, a lower cut-off value of 90 ng/l allowed a correct classification of 90% of the subjects. However, a large variance of the reference values, partly explained by the potential contamination of the reference population with presymptomatic dementia patients, may limit the use of reference limits based on living subjects. We propose that the issue of defining reference limits for both cerebrospinal fluid tau and Aβ42 may ultimately be settled by studying large numbers of autopsy-proven neurologically intact individuals only.
The influence of smoking on plasma homocysteine and cysteine levels in passive and active smokers
Authors: Sobczak Andrzej , Wardas Wladyslaw , Zielinska-Danch Wioleta , Pawlicki Krzysztof
Published: August 2004

Total plasma homocysteine (tHcy) and cysteine (tCys) levels are associated with cardiovascular diseases. One of the determinants that influence their levels is cigarette smoking. The aim of this study was to determine the relationship between plasma levels of both amino acids and urinary cotinine concentration as a reliable biomarker of tobacco smoke exposure. One hundred and seventeen volunteers (61 women and 56 men) aged 19–60 years (mean 40.3±11.0) were included in the study. The study subjects were qualified into non-smokers, passive smokers and active smokers based upon the urinary cotinine concentration. In each particular group, plasma tHcy and tCys levels were measured and evaluated in the whole population and separately in women and men. Statistically insignificant differences in plasma tHcy and tCys levels in the whole group of passive smokers in comparison with non-smokers were observed (11.47 vs. 10.94 μmol/l, p=0.414, and 253.0 vs. 266.9 μmol/l, p=0.163, respectively). However, statistically significant differences in plasma tHcy levels (13.29 vs. 10.94 μmol/l, p=0.011) and in plasma tCys levels (218.2 vs. 266.9 μmol/l, p<0.001) were found in the whole group of active smokers compared with nonsmokers. The Pearson's coefficient (r) for the correlation between plasma tHcy level and urinary cotinine concentration was r=0.630 (p<0.001) in the whole group of active smokers and r=0.480 (p=0.003) in the whole group of passive smokers. The correlation between plasma tCys level and urinary cotinine concentration in both study groups was insignificant. Similar results were obtained when calculated separately for men and women. The results suggest that cigarette smoking is a strong determinant of plasma tHcy level, but it is not a determinant of plasma tCys level.
A different approach to analyzing age-related HbA1c values in non-diabetic subjects
Authors: Polneau Sandrine Vallée , Lasserre Virginie , Fonfrède Michèle , Delattre Jacques , Bénazeth Simone
Published: August 2004

Using appropriate statistical tests and taking into account the analytical performance of hemoglobin A

Fasting plasma glucose and HbA

We first checked the normality of HbA
Ratio of urinary free immunoglobulin light chain κ to λ in the diagnosis of Bence Jones proteinuria
Authors: Nakano Takanari , Nagata Atsuo , Takahashi Hidenori
Published: August 2004

The aim of this study was to evaluate the diagnostic efficacy of the ratio of urinary free light chain (FLC) kappa to lambda (κ/λ ratio) for the detection of Bence Jones protein (BJP). Urine specimens were collected from 243 patients suspected of having BJP. Immunofixation identified 59 BJP-positive specimens among them. The κ/λ ratios of all specimens were determined by FLC immunoassays and then the cutoffs for the κ/λ ratio were defined as 5.5 for BJP κ and 0.1 for BJP λ by ROC curve analyses. Using the cutoffs, we detected abnormal κ/λ ratios in 51 (86%) of the 59 BJP-positives and 11 (6%) of the 184 BJP-negatives identified by the results of immunofixation. High-resolution urinary protein electrophoresis (UPE), a sensitive method for BJP screening, showed almost equal sensitivity to the κ/λ ratio, detecting monoclonal band(s) in 52 (88%) of the 59 BJP-positives. However, in UPE analysis these positive specimens should be followed by redundant immunofixation analysis to determine the isotypes. We further evaluated the combination method of FLC assays with UPE that correctly diagnosed 82% of the specimens as positive or negative for BJP, with only two false-negative results. These results suggest that quantitative FLC immunoassays provide an alternative or complementary method for the detection of BJP.
Influence of blood collection in plastic vs. glass evacuated serum-separator tubes on hormone and tumour marker levels
Authors: Smets Eva M. L. , Dijkstra-Lagemaat Josien E. , Blankenstein Marinus A.
Published: August 2004

Introduction of preanalytical automation in our laboratory required the use of plastic blood collection tubes. Because of possible interference caused by adsorption of components to the plastic wall and because there is virtually no literature on this subject, we investigated the influence of collection of serum in plastic tubes on the results of nearly all our immunoassays for hormones and tumour markers. Blood from healthy volunteers was collected simultaneously in glass and plastic tubes, or sera prepared from blood collected in glass tubes were brought into the plastic tubes under investigation. Hormone and tumour marker levels were measured in the pairs thus obtained. Results were analysed using paired t-tests or Wilcoxon signed rank tests. We found small but statistically significant differences (p<0.05) between glass and plastic for free triiodothyronine, progesterone, prolactin, prostate-specific antigen and pregnancy-associated plasma protein-A. Non-significant trends (0.05<p<0.15) were seen with α-foetoprotein, androstenedione, BR (an assay for carbohydrate antigen 15.3), human chorionic gonadotropin and testosterone. Passing and Bablok regression analysis, however, revealed no clinically relevant differences (slopes ranged from 0.89 for progesterone to 1.07 for pregnancy-associated plasma protein-A, while intercepts were all small). We concluded that a switch to plastic blood collection tubes could occur without any implications for the interpretation of results.
Multicenter evaluation of a new immunoassay for procalcitonin measurement on the Kryptor® System
Authors: Steinbach Gerald , Rau Bettina , Debard Anne-Lise , Javourez Jean-François , Bienvenu Jacques , Ponzio Antonio , Bonfà Andrea , Hubl Walter , Demant Thomas , Külpmann W.-R. , Buchholz Jana , Schumann Gerhard
Published: August 2004

We compared the manually performed LUMItest

The new Kryptor

The FAS of the new Kryptor

The performance characteristics of the Kryptor
Analytical performance of the Albumin Cobalt Binding (ACB®) test on the Cobas MIRA® Plus analyzer
Authors: Gidenne Stéphane , Ceppa Franck , Fontan Eleonore , Perrier Françoise , Burnat Pascal
Published: August 2004

Recently a new biological marker, Ischemia Modified Albumin (IMA
Beyond cholesterol - inflammatory cytokines, the key mediators in atherosclerosis
Authors: Mangge Harald , Hubmann Holger , Pilz Stefan , Schauenstein Konrad , Renner Wilfried , März Winfried
Published: August 2004

The development of atherosclerotic lesions encompasses a cascade of cellular and molecular responses that can at best be characterized as an inflammatory process, and exhibits striking similarities to autoimmune diseases, such as rheumatoid arthritis. Chemokines, cytokines and their receptors are critically involved in initiation and perpetuation of atherosclerosis, and they play important roles at all levels in the pathogenesis of this disease. In the present article, the currently available information on cytokines and chemokines as key mediators in atherosclerosis is reviewed. Furthermore, based on recent experiences of our own with very early stages of atherosclerosis, possible new ways to make use of these parameters toward improved early detection, prevention and treatment of this disease are indicated.
The emerging value of P-selectin as a disease marker
Authors: Kappelmayer János , Nagy Béla , Miszti-Blasius Kornél , Hevessy Zsuzsa , Setiadi Hendra
Published: August 2004

Activated platelets are key components in many arterial disorders. P-selectin is an activation-dependent platelet receptor, which is also identified in endothelial cells. Together with E-and L-selectin it constitutes the selectin family. These transmembrane proteins have continued to attract great interest as they support rapid and reversible cell adhesion in flow systems and thus play an essential role in multicellular interactions during thrombosis and inflammation. Similarly to other lectins, selectins bind to different glycoconjugates with varying affinities. Protein ligands, equipped with the appropriate carbohydrate and sulfate moieties for P-selectin binding, have been identified in normal peripheral blood leukocytes and several non-hematopoietic organs, as well as on cancer cells. For diagnostic purposes, P-selectin can readily be detected on the platelet surface by flow cytometry and by ELISA as a soluble ligand in the plasma. Along with other markers, these data can be used in the assessment of platelet activation status. Such results bear clinical significance since P-selectin has been implicated in the pathogenesis of widespread disorders including coronary artery disease, stroke, diabetes and malignancy.
Up-regulation of reactive oxygen species (ROS) and resistance to Fas-mediated apoptosis in the C33A cervical cancer cell line transfected with IL-18 receptor
Authors: Yoon Do-Young , Cho Young-Sik , Park Joo-Won , Kim Soo-Hyun , Kim Jong-Wan
Published: August 2004

Cervical cancer cells were transfected with a newly discovered interleukin (IL)-18 receptor to investigate the effect of endogenous IL-18 on the regulation of immune-related factors such as Fas (CD95/Apo-1)/Fas ligand and intercellular adhesion molecules. Transfection of the IL-18 receptor selectively induced a slight enhancement of the Fas via the up-regulation of intracellular reactive oxygen species and IL-18 in cervical carcinoma C33A cells, whereas there were no effects on the expression of p53, intercellular adhesion molecules-1 and Fas ligand. Neither IL-18 receptor transfection nor recombinant IL-18 enhanced interferon-γ production in C33A cells. Thus, IL-18 receptor transfection induced IL-18 expression and enhanced intracellular reactive oxygen species and Fas expression in C33A cells in an interferon-γ-independent pathway. However, treatment with agonistic anti-Fas antibody did not induce the apoptosis of C33A/IL-18 receptor transfectants, suggesting that either reactive oxygen species play a key role in resisting the Fas-induced apoptosis of C33A cells, or Fas was not functional. These results show that C33A/IL-18 receptor cells are resistant to the apoptosis and thus can survive against the immune surveillance and activated immune cells. Our results thus suggest that IL-18 and IL-18 receptor, together, may play a role in immunoregulation or in inflammation by augmenting the levels of IL-18 and reactive oxygen species in C33A cells.