bluuebunny/crossref_metadata_2025 huggingface dataset:
Rounding Algorithms for a Geometric Embedding of Minimum Multiway Cut
Authors: Karger David R. , Klein Philip , Stein Cliff , Thorup Mikkel , Young Neal E.
Published: August 2004

Given an undirected graph with edge costs and a subset of k≥3 nodes called terminals, a multiway, or k-way, cut is a subset of the edges whose removal disconnects each terminal from the others. The multiway cut problem is to find a minimum-cost multiway cut. This problem is Max-SNP hard. Recently, Calinescu et al. (Calinescu, G., H. Karloff, Y. Rabani. 2000. An improved approximation algorithm for MULTIWAY CUT. J. Comput. System Sci. 60(3) 564–574) gave a novel geometric relaxation of the problem and a rounding scheme that produced a (3/2−1/k)-approximation algorithm.

In this paper, we study their geometric relaxation. In particular, we study the worst-case ratio between the value of the relaxation and the value of the minimum multicut (the so-called integrality gap of the relaxation). For k=3, we show the integrality gap is 12/11, giving tight upper and lower bounds. That is, we exhibit a family of graphs with integrality gaps arbitrarily close to 12/11 and give an algorithm that finds a cut of value 12/11 times the relaxation value. Our lower bound shows that this is the best possible performance guarantee for any algorithm based purely on the value of the relaxation. Our upper bound meets the lower bound and improves the factor of 7/6 shown by Calinescu et al.

For all k, we show that there exists a rounding scheme with performance ratio equal to the integrality gap, and we give explicit constructions of polynomial-time rounding schemes that lead to improved upper bounds. For k=4 and 5, our best upper bounds are based on computer-constructed rounding schemes (with computer proofs of correctness). For general k we give an algorithm with performance ratio 1.3438−εk.

Our results were discovered with the help of computational experiments that we also describe here.
Efficiency Loss in a Network Resource Allocation Game
Authors: Johari Ramesh , Tsitsiklis John N.
Published: August 2004

We explore the properties of a congestion game in which users of a congested resource anticipate the effect of their actions on the price of the resource. When users are sharing a single resource, we establish that the aggregate utility received by the users is at least 3/4 of the maximum possible aggregate utility. We also consider extensions to a network context, where users submit individual payments for each link in the network they may wish to use. In this network model, we again show that the selfish behavior of the users leads to an aggregate utility that is no worse than 3/4 of the maximum possible aggregate utility. We also show that the same analysis extends to a wide class of resource allocation systems where end users simultaneously require multiple scarce resources. These results form part of a growing literature on the “price of anarchy,” i.e., the extent to which selfish behavior affects system efficiency.
Some Properties of the Augmented Lagrangian in Cone Constrained Optimization
Authors: Shapiro Alexander , Sun Jie
Published: August 2004

A large class of optimization problems can be modeled as minimization of an objective function subject to constraints given in a form of set inclusions. In this paper, we discuss augmented Lagrangian duality for such optimization problems. We formulate the augmented Lagrangian dual problems and study conditions ensuring existence of the corresponding augmented Lagrange multipliers. We also discuss sensitivity of optimal solutions to small perturbations of augmented Lagrange multipliers.
Use of Verapamil as a Potential P-Glycoprotein Inhibitor in a Patient with Refractory Epilepsy
Authors: Summers Monica A , Moore J Layne , McAuley James W
Published: August 2004

OBJECTIVE

To describe a patient in whom we used adjunctive verapamil therapy was used for its P-glycoprotein inhibitory effects.

CASE SUMMARY

Verapamil was added to the antiepileptic drug regimen of a 24-year-old woman with intractable epilepsy. The average time interval between hospitalizations for complex partial status doubled. The addition of verapamil greatly improved overall seizure control and subjective quality of life in this pharmacoresistant patient.

DISCUSSION

The overexpression of P-glycoprotein in the central nervous system may be one mechanism of pharmacoresistance in patients with epilepsy. The calcium-channel blocker verapamil is a known inhibitor of P-glycoprotein and may function to block P-glycoprotein—modulated efflux of antiepileptic drugs in the brain, thereby raising the intracellular concentration of antiepileptic drugs and ultimately decreasing seizure burden in patients with refractory epilepsy.

CONCLUSIONS

Verapamil may offer pharmacoresistant patients hope of improved seizure control due to its potential P-glycoprotein inhibitory effects.
Anti-Xa Monitoring of Enoxaparin for Acute Coronary Syndromes in Patients with Renal Disease
Authors: Ma Jessica M , Jackevicius Cynthia A , Yeo Erik
Published: August 2004

BACKGROUND

There are limited data on dosing of enoxaparin in patients with renal disease due to the routine exclusion of this population in clinical trials. To account for the potentially delayed drug elimination in these patients, we developed guidelines for adjusting enoxaparin dosing based on anti-Xa monitoring.

OBJECTIVE

To evaluate anti-Xa level monitoring, resulting from the standards of practice as set out by our hospital's guidelines for enoxaparin dosing in renally impaired patients.

METHODS

A total of 72 separate acute coronary syndrome patient admissions were retrospectively reviewed. All patients had anti-Xa levels taken and creatinine clearance values <30 mL/min during enoxaparin therapy.

RESULTS

The average trough anti-Xa level at the once- and twice-daily doses was 0.40 and 0.72 IU/mL, respectively. With twice-daily dosing, only 6% of the trough concentrations were in the target range of 0.2–0.3 IU/mL compared with 36% with once-daily dosing. Of the 22 patients who had a change of dosing frequency from twice to once daily, 5% of trough anti-Xa levels were ≤0.5 IU/mL with twice-daily versus 68% with once-daily dosing.

CONCLUSIONS

Although the relationship between anti-Xa activity, efficacy, and adverse effects has not been definitively established, anti-Xa levels can assist with dosing of enoxaparin in renally impaired patients. Our hospital guidelines are effective in adjusting dosing to reach target anti-Xa levels.
Physical and Chemical Compatibility of Daptomycin with Nine Medications
Authors: Lai Jan-Ji , Brodeur Stephanie K
Published: August 2004

BACKGROUND

Hospitalized patients with serious gram-positive infections tend to require concomitant therapy. Unfortunately, a number of antimicrobial agents have demonstrated incompatibility with other agents commonly administered intravenously.

OBJECTIVE

To evaluate the physical compatibility and chemical stability of the novel lipopeptide antibiotic daptomycin, at 20 mg/mL, with 9 commonly administered intravenous medications: aztreonam, ceftazidime, ceftriaxone, dopamine, gentamicin, fluconazole, heparin, levofloxacin, and lidocaine to support simultaneous Y-site administration.

METHODS

Daptomycin was admixed with each medication separately in NaCl 0.9%, incubated at room temperature, and assayed at 30, 60, and 120 minutes. Physical stability was assessed by visual inspection and by turbidity measurements. Chemical stability was assessed by HPLC analysis using standard methods.

RESULTS

All 9 daptomycin admixtures remained clear solutions, free of visible particulates. There were also few changes in turbidity (range 0 to −0.7 nephelometric turbidity units) during the study. In general, pH changes were within ± 0.06 of baseline readings for all admixtures. HPLC analysis indicated no significant reduction (<4%) in daptomycin potency after 120 minutes at room temperature compared with baseline values in all 9 admixtures tested. In addition, there was no significant reduction (<5%) in potency compared with baseline values of the 9 medications tested in the daptomycin admixtures.

CONCLUSIONS

The results of this study indicate that solutions of 9 commonly administered intravenous medications simultaneously Y-site administered with daptomycin are stable and compatible, based on both physical and chemical potency analyses.
Effect of 24-Hour Intravenous Tubing Set Change on the Sterility of Repackaged Fat Emulsion in Neonates
Authors: Reiter Pamela D , Robles Janie , Dowell Elaine B
Published: August 2004

BACKGROUND

Duration of intravenous fat emulsion (IVFE) infusions, precise method of administration (manufactured bottle vs repackaged syringe), and interval for administration set change continue to be debated.

OBJECTIVE

To determine the contamination rate associated with replacing IVFE administration sets every 24 hours in newborn infants receiving fat emulsion repackaged into unit-of-use syringes.

METHODS

This was a prospective, microbiologic study of 90 administration sets used in 19 neonates. IVFE samples were obtained from administration sets at the end of a 19– to 23–hour infusion and prior to daily tubing set change from infants who received repackaged IVFE. Samples of IVFE (1–3 mL) were aseptically removed at the catheter connection site proximal to the patient, transferred into BACTEC PEDSPlus culture media, and continuously monitored for 5 days to detect gram-positive and gram-negative organisms, as well as yeast.

RESULTS

Two samples (2.27%) grew coagulase-negative Staphylococcus. Both samples were from the same asymptomatic patient and were obtained on consecutive days. A blood sample obtained through this infant's central catheter grew the same organism and suggested catheter hub colonization as the primary site of microbe origin.

CONCLUSIONS

Microbial contamination of IVFE infusion sets changed at 24–hour intervals, using unit-of-use syringes in neonates, was low at 2.2%.
Celecoxib-Induced Methemoglobinemia
Authors: Kaushik Prashant , Zuckerman Steven J , Campo Nicholas J , Banda Venkatramana R , Hayes Scott D , Kaushik Richa
Published: August 2004

OBJECTIVE

To report a case of acute methemoglobinemia in a patient treated with celecoxib for osteoarthritis.

CASE SUMMARY

A 72-year-old African American man developed an acute confusional state (ACS) one month after receiving celecoxib for osteoarthritis of his knee joints. There was no other identifiable cause of ACS such as any recognized cause of metabolic encephalopathy, meningoencephalitis, cerebrovascular accident, or drug intoxication. He was found to have severe methemoglobinemia (serum methemoglobin fraction 9%; reference range 0–0.2). His symptoms improved substantially, and serum methemoglobin levels decreased to 0.7% after the initiation of methylene blue therapy. He was discharged on oral riboflavin and ascorbic acid and was advised not to restart celecoxib therapy. He had not shown any recurrence of the symptoms at a follow-up visit 2 months after the withdrawal of celecoxib.

DISCUSSION

Celecoxib is a nonsteroidal antiinflammatory drug that selectively inhibits cyclooxygenase-2. Acute methemoglobinemia can present as a syndrome of nonspecific symptoms such as headache, nausea, fatigue, dyspnea, and lethargy; these may progress to respiratory depression, coma, shock, seizures, and death. Although acute methemoglobinemia has been reported with the use of several drugs, including sulfonamides, as of August 13, 2004, this is the first case report of severe methemoglobinemia manifesting as ACS with celecoxib therapy. Use of the Naranjo probability scale indicated a probable relationship between the clinical manifestations of methemoglobinemia and celecoxib therapy in this patient.

CONCLUSIONS

Celecoxib can be associated with acute methemoglobinemia. Prompt diagnosis of this condition, withdrawal of celecoxib, and treatment with the antagonists (methylene blue, ascorbic acid, riboflavin) can reverse this potentially serious condition.
Increased serum maternal levels of the HER2 oncoprotein p105 ectodomain in preeclampsia
Authors: Tse Chantal , Lefevre Guillaume , Berkane Nadia , Flahault Antoine , Toumi Karine , Brault Didier , Capeau Jacqueline , Uzan Serge
Published: August 2004

HER2/ERBB2 protein is a 185 kDa transmembrane growth factor receptor whose extracellular domain, a 105 kDa fragment (p105), can be released from cell surfaces by proteolytic cleavage. The aim of our study was to compare serum p105 concentrations in normal and pathological pregnancies and to determine whether any correlation exists between preeclampsia and p105 levels. Serum p105 was assayed in 96 nonpregnant women and 89 pregnant women (26 normotensive, 14 normotensive with a history of preeclampsia or fetal hypotrophy, 10 with chronic hypertension, 10 with gestational hypertension and 29 with preeclampsia). Median serum p105 levels (median; 95% confidence interval) were higher in the preeclampsia group (13.9 μg/l; 12.8–16.1 μg/l) than in the normotensive (11.7 μg/l; 10.6μ13.3 μg/l; p<0.05) or non-pregnant groups (9.3 μg/l; 8.9–9.6 μg/l; p<0.001). There were no significant differences between the other pregnancy groups. In the normotensive group, serum p105 was correlated with the number of gestations (r=0.46; p<0.05), parity (r=0.39; p<0.05) and placenta weight (r=0.61; p<0.05). In preeclamptic women, serum p105 correlated with parity (r=0.46; p<0.05). Serum p105 concentrations above 11.9 μg/l were associated with a high odds ratio (OR) for onset of preeclampsia (after adjustment for parity OR=9.0; 95% CI=2.3–36.0; p<0.005). Preeclampsia is associated with increased serum p105 concentrations, which may be related to increased fetomaternal cell traffic.
Determination of urinary glyoxal and methylglyoxal by high-performance liquid chromatography
Authors: Akira Kazuki , Matsumoto Yui , Hashimoto Takao
Published: August 2004

Carbonyl stress compounds such as glyoxal and methylglyoxal have been recently attracting much attention because of their possible clinical significance in chronic and age-related diseases. A high-performance liquid chromatographic procedure has been developed for the simultaneous quantitation of glyoxal and methylglyoxal in human urine. The assay is based on the reaction of these compounds with 1,2-diamino-4,5-dimethoxybenzene to form fluorescent adducts, which are separated by reversed-phase highperformance liquid chromatography in a total run time of 45 minutes and quantitated fluorometrically using 2,3-pentanedione as an internal standard. Derivatization is performed for diluted urine (100–120 mOsm/kg H
Antioxidants in patients with hyperthyroidism
Authors: Mayer Ljiljana , Romic Željko , Škreb Franjo , Bačic-Vrća Vesna , Čepelak Ivana , Žanic-Grubišić Tihana , Kirin Marijan
Published: August 2004

Hyperthyroidism is a hypermetabolic state accompanied by increased oxygen utilization, increased production of reactive oxygen species and consequentially measurable changes in antioxidative factors. Therefore, the activities of whole blood glutathione peroxidase (GPx) and erythrocyte superoxide dismutase (SOD), total antioxidant status (TAS) in serum and erythrocytes, and serum urate and transferrrin concentrations were determined in 70 women: 14 with newly diagnosed Graves' disease (group A); 28 with hyperthyroidism on therapy with methimazole (group B, divided into two subgroups, B1 and B2) and 28 healthy women (group C).

In comparison with control group C, GPx activity was significantly decreased in all patient groups (p<0.05), whereas SOD activity was significantly decreased in group A (p<0.01) and significantly increased in group B (p<0.01). In comparison with the control group, serum TAS activity was significantly decreased in group A, and erythrocyte TAS activity in all patient groups.

Study results suggest that the impaired antioxidative factor balance leads to the development and presence of oxidative stress in women with hyperthyroidism. The severity of these alterations, considered contradictory by some authors, appears to depend on the use of therapy.
Biochemical diagnosis of impaired left ventricular ejection fraction - comparison of the diagnostic accuracy of brain natriuretic peptide (BNP) and amino terminal proBNP (NT-proBNP)
Authors: Mueller Thomas , Gegenhuber Alfons , Poelz Werner , Haltmayer Meinhard
Published: August 2004

The aim of the present investigation was to evaluate the diagnostic accuracy of brain natriuretic peptide (BNP) and amino terminal proBNP (NT-proBNP) for the detection of mild/moderate and severe impairment of left ventricular ejection fraction (LVEF). In 180 subjects BNP and NT-proBNP were measured by two novel fully automated chemiluminescent assays (Bayer and Roche methods). LVEF as determined by echocardiography was categorized as normal (>60%), mildly/moderately reduced (35–60%) and severely diminished (<35%). Discriminating between patients with LVEF<35% (n=32) and subjects with LVEF ≥35% (n=148), receiver-operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) of 0.912 for BNP and of 0.896 for NT-proBNP (difference 0.016, p=0.554). In contrast, BNP displayed an AUC of 0.843and NT-proBNP an AUC of 0.927 (difference of 0.084, p=0.034) when comparing patients with LVEF 35–60% (n=37) and individuals with LVEF >60% (n=111). Evaluation of discordant false classifications at cut-off levels with the highest diagnostic accuracy showed advantages for BNP in the biochemical diagnosis of LVEF<35% (4 misclassifications by BNP and 25 by NT-proBNP, p<0.001) and for NT-proBNP in the detection of LVEF 35–60% (25 misclassifications by BNP and 7 by NT-proBNP, p=0.002). In conclusion, the present study indicates a different diagnostic accuracy of BNP and NT-pro-BNP for the detection of mildly/moderately reduced LVEF and severely diminished LVEF. Advantages of BNP may be advocated for the biochemical diagnosis of more severely impaired LVEF, while NT-proBNP might be a more discerning marker of early systolic left ventricular dysfunction.
Urine albumin excretion in acute ischaemic stroke is related to serum interleukin-6
Authors: Dziedzic Tomasz , Slowik Agnieszka , Szczudlik Andrzej
Published: August 2004

Background and purpose: Several studies show a link between microalbuminuria and markers of inflammation. Increased urine albumin excretion accompanies acute ischaemic stroke. The mechanisms responsible for microalbuminuria in acute stroke patients remain unclear. The goal of this study was to determine if there is a relationship between urine albumin excretion and interleukin-6, a key mediator of acute phase reaction. Methods: Nineteen acute ischaemic stroke patients and 13 controls matched for age, sex and cardiovascular risk factors were included. Serum interleukin-6 level was measured on the 2nd day of stroke at 06:00 am, 10:00 am, 06:00 pm and 10:00 pm using ELISA method. Urine albumin excretion was determined using immunonephelometric method. Results: Interleukin-6 level and urine albumin excretion were significantly higher in stroke patients than in controls. There was a significant correlation between interleukin-6 level and urine albumin excretion in stroke patients (R=−0.60 at 06:00 am; R=−0.49 at 10:00 am; R=−0.64 at 06:00 pm; R=−0.54 at 10:00 pm) but not in controls. Conclusions: Urine albumin excretion in acute ischaemic stroke is related to serum interleukin-6.
The discordance rate, a new concept for combining diagnostic decisions with analytical performance characteristics. 2. Defining analytical goals applied to the diagnosis of type 2 diabetes by blood glucose concentrations
Authors: Haeckel Rainer , Wosniok Werner
Published: August 2004

A novel statistical approach has recently been described to estimate diagnostic “errors” in method comparison studies. This procedure requires a population-based probability, p

The new concept was then applied in a reverse mode by determining the analytical variability of glucose concentrations for a fixed discordance rate diagnosing type 2 diabetes. If a combined discordance rate (sum of positive and negative discordances) of 5% is allowed, a maximal imprecision of 3.7% can be tolerated in the absence of bias. In the presence of a 3.0% bias, the allowable imprecision must be reduced to 2.8%. The relationship between bias and imprecision followed a complex function and not a simple linear model. These allowable limits were achieved with venous plasma in the fasting state.

The allowable analytical specifications were slightly more stringent with capillary blood. After a 2 h glucose challenge, higher error rates could be tolerated, indicating that post-load glucose concentrations have a higher diagnostic efficiency than fasting levels. The new concept has the advantage that it is derived from patient's samples in relation to diagnostic requirements.
Effects of some pre-analytical conditions on the measurement of homocysteine and cysteine in plasma
Authors: Zighetti Maddalena L. , Chantarangkul Veena , Lombardi Rossana , Lecchi Anna , Cattaneo Marco
Published: August 2004

The association of hyperhomocysteinemia and hypercysteinemia with the risk of arterial and venous thrombosis is well documented. While it is known that standardized pre-analytical conditions are necessary for reliable measurement of plasma total homocysteine, the effects of pre-analytical conditions on cysteine measurement are less well known. The aim of this study was to evaluate the effects of pre-analytical conditions on the measurement of homocysteine and cysteine. We observed that the concentration of total homocysteine in plasma increased significantly with time (38% after 6 h), whereas total cysteine decreased (5% after 2h) when blood anticoagulated with ethylenediaminetetraacetic tripotassium salt was kept at room temperature. These changes were minimized when acidic citrate dextrose was used as an anticoagulant and were abolished when blood samples were immediately placed on crushed ice, independently of the anticoagulant. Storage of plasma for 72h at room temperature induced a small (≅6%), but significant, decrease in cysteine when blood was collected in ethylenediaminetetraacetic tripotassium salt. In contrast, homocysteine was stable in plasma for 72h, independently of the anticoagulant used. In conclusion, if blood samples for plasma total homocysteine and cysteine measurement cannot be kept on ice, they should be collected in acidic citrate dextrose to minimize the artifactual changes.
Anti-nucleosome, anti-chromatin, anti-dsDNA and anti-histone antibody reactivity in systemic lupus erythematosus
Authors: González Concepción , Garcia-Berrocal Belen , Herráez Oscar , Navajo José Alejandro , ManuelGonzález-Buitrago José
Published: August 2004

Anti-nucleosome (anti-chromatin) antibodies play a key role in the pathogenesis of systemic lupus erythematosus (SLE). The objective of the present study was to determine the clinical significance of anti-nucleosome (anti-chromatin) antibodies, anti-dsDNA antibodies and anti-histone antibodies in patients with SLE in relation to patients with positive nuclear antibodies and healthy controls. We measured anti-nucleosome (anti-chromatin) antibodies, anti-dsDNA antibodies and anti-histone antibodies in 70 patients with SLE, 35 antinuclear antibody (ANA)-positive subjects without autoimmune disease and 35 blood donors. All antibodies were determined by enzyme-linked immunosorbent assay (ELISA). We obtained the receiver operating caracteristic (ROC) curve and the area under the curve (AUC) for each autoantibody. Likewise, we obtained the sensitivity, specificity and positive and negative likelihood ratios for each autoantibody. The highest AUC was obtained for anti-nucleosome (0.898) and the lowest AUC for a kit for anti-dsDNA (0.725). Stratification of the control group (ANA-positive subjects without autoimmune disease and blood donors) produced significant changes in the AUCs; all AUCs decreased when ANA-positive patients without autoimmune disease were considered as controls and all AUCs increased when blood donors were considered as controls. These effects were less marked in anti-dsDNA antibodies. We observed discrepancies between kits (anti-nucleosome and anti-chromatin and two for anti-dsDNA). The highest sensitivity for SLE was obtained for anti-nucleosome antibodies (86%) and the highest specificity was obtained for anti-dsDNA antibodies (90%). In conclusion, anti-nucleosome and anti-chromatin kits show different degrees of clinical accuracy due to the cut-off selected by the manufacturer. Once the kits with the best performance and the optimal cut-offs have been selected, anti-nucleosome antibodies and anti-dsDNA antibodies provide similar information in established SLE.
Age dependence of serum β-N-acetylhexosaminidase (NAG) activity
Authors: Oláh Anna V. , Price Robert G. , Csáthy László , Országh Éva , Oláh Éva , Varga József
Published: August 2004

Serum N-acetyl-β-D-glucosaminidase (NAG; EC 3.2.1.30) is a hexosaminidase and may be a predictor of vascular injury, e.g., in infant respiratory distress syndrome, pneumonia, broncho-pulmonary dysplasia and necrotizing enterocolitis. To estimate the new diagnostic prospects we have modified our urinary NAG assay. In this sensitive colorimetric micro-assay, VRA-GlcNAc was used as a substrate. In the present study the age dependence of serum NAG activity was investigated in newborn babies, infants (1–24 months), children (2–18 years) and adults (19–80 years). Serum NAG activity was found to be age-dependent; it is higher in early childhood (11–59 U/l) but decreases to a constant value at the age of 1–2 years. After the age of 2 years it is similar to adults' NAG (10–30 U/l). In pediatrics age-matched reference ranges must be taken into consideration.
Near-patient testing for infection using urinalysis and immuno-chromatography strips
Authors: Pugia Michael J. , Sommer Ronald G. , Kuo Hai-Hang , Corey Paul F. , Gopual Darryl L. , Lott John A.
Published: August 2004

Urinary tract infections require costly confirmatory tests such as a urine culture to establish the diagnosis. Elimination of the culture step would save resources; diagnosis and treatment could begin in hours rather than days. We tested a new dip-and-read strip that uses immuno-chromatography (IC) to detect infectious agents in urine. We used a goat-derived polyclonal antibody with reactivity to the cell-wall proteins of
Generation of eight adjacent mutations in a single step using a site-directed mutagenesis kit
Authors: Cabré Anna , Girona Josefa , Zalba Guillermo , Moreno María-Ujué , Díez Javier , Masana Lluís
Published: August 2004

Studies that characterize transcriptional regulatory elements involve the site-directed mutagenesis methodology to generate deletions, insertions and point mutations. Commercial PCR-based system kits are widely used to introduce up to four base changes in a target sequence. Sequential mutagenesis experiments allow more than four bases to be altered. In this work, we show that the QuikChange site-directed mutagenesis kit developed by Stratagene, with an optimum primer design, can change eight adjacent bases. This approach allows us to study the effect of DNA sequence changes on functionality of specific sequences from gene target regions, including promoters, exons and introns. As a result of this methodology, a faster and cheaper way of introducing this number of mutations is achieved in a single step with only one pair of primers, thus reducing the possibility of potential random mutation in the rest of the target sequence.
Reference change values and power functions
Authors: Canadell Natàlia Iglesias , Petersen Per Hyltoft , Jensen Esther , Ricós Carmen , Jørgensen Per E.
Published: August 2004

Repeated samplings and measurements in the monitoring ofpatients to look for changes are common clinical problems. The “reference change value”, calculated as z
Comparison of three commercial assays for the measurement of 17α-hydroxyprogesterone (17α-OHPR): limitations of the quality control system
Authors: Meier Ursula , Schnabel Claudia , Kunz Dagmar , Driesch Reinhard , Gressner Axel M.
Published: August 2004

The measurement of 17α-hydroxyprogesterone (17α-OHPR) is of value for the diagnosis and management of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. In the central laboratory from 2000 to 2002, we observed, using the assay from the manufacturer DSL, an elevation of the moving average of 17α-OHPR concentrations and a number of adrenocorticotropic hormone (ACTH) stimulation tests despite the lack of any changes to the internal and external quality control, of which the criteria were continuously fulfilled. We studied a population of n=49 patients for the measurement of 17α-OHPR, with and without extraction, to evaluate the quality of different commercially available radioimmunoassays. The internal and external quality controls were successful in determining 17α-OHPR. An excellent measurement and correlation of 17α-OHPR was expressed with the assay from the manufacturer IBL without extraction and from the manufacturer DSL with extraction. The quantitative determination of 17α-OHPR requires adequate specificity and accuracy of the 17α-OHPR radioimmunoassays. The results show that internal and external quality control systems are not sufficient to resolve analytical problems described in this study.
Analysis of candidate genes in Polish families with obesity
Authors: Malczewska-Malec Malgorzata , Wybranska Iwona , Leszczynska-Golabek Iwona , Partyka Lukasz , Hartwich Jadwiga , Jabrocka Agata , Kiec-Wilk Beata , Kwasniak Malgorzata , Motyka Marcin , Dembinska-Kiec Aldona
Published: August 2004

This study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-γ

The 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated.

The single gene mutations such as C

We conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.
Detection of the Arg702Trp, Gly908Arg and Leu1007fsinsC polymorphisms of the NOD2/CARD15 gene by real-time PCR with melting curve analysis
Authors: Rüegg Christian , Hersberger Martin , Wusk Barbara , Rentsch Katharina , Kullak-Ublick Gerd A. , Eckardstein Arnold von , Maly Friedrich E.
Published: August 2004

Crohn's disease is a complex disorder, with multiple genetic traits. A frameshift mutation (Leu1007fsinsC) and two missense mutations (Gly908Arg and Arg702Trp) in the NOD2/CARD15 gene are strongly associated with susceptibility to Crohn's disease. The presence of one of these risk alleles confers a 2- to 4-fold increase in the risk of developing Crohn's disease, and the presence of two mutant alleles increases the risk over 20-fold.

To facilitate the analysis of these polymorphisms, we developed three LightCycler assays to detect the missense mutations Arg702Trp and Gly908Arg and the frameshift mutation Leu100fsinsC in the
Rapid detection of mutations in Wilson disease gene ATP7B by DNA strip technology
Authors: Huster Dominik , Weizenegger Michael , Kress Stefan , Mössner Joachim , Caca Karel
Published: August 2004

Wilson disease leads to severe hepatic and neurological pathology resulting from cellular copper overload in the respective tissue. Although the affected gene,
Moderate exercise with a dietary vitamin C and E combination protects against streptozotocin-induced oxidative damage to the blood and improves fetal outcomes in pregnant rats
Authors: Naziroğlu Mustafa , Şimşek Mehmet , Kutlu Mehmet
Published: August 2004

A considerable amount of clinical and experimental evidence now exists suggesting that many biochemical pathways strictly associated with diabetes increase the production of reactive oxygen species (ROS). However, daily moderate exercise and vitamins C and E(VCE ) supplementation can be beneficial to diabetes due to reducing blood glucose and free radical production. In the present study, we investigated the effect of VCE and moderate exercise on lipid peroxidation (MDA) and scavenging enzyme activity in the blood of STZ-induced diabetic pregnant rats.

Fifty female Wistar rats were used and were randomly divided into five groups. The first and second were used as the control and pregnant control groups, respectively. The third group was the pregnant diabetic group. The fourth group was the diabetic-pregnant-exercise group. VCE-supplemented feed was given to pregnant-diabetic-exercise rats constituting the fifth group. Animals in the exercised groups were moderately exercised daily on a treadmill (16.1 m/min, 45 min/d) for three weeks (five days a week). Diabetes was induced on day zero of the study. Body weights in the five groups were recorded weekly. Plasma and red blood cell (RBC) samples were taken from all animals on day 20.

Glutathione peroxidase (GSH-Px), catalase and reduced glutathione (GSH) levels in plasma and RBCs, glucose, vitamins A, E and β-carotene in plasma, the number of fetuses, and body weight were lower in pregnant diabetic rats than in control animals, whereas there was a significant increase in platelet counts and plasma and RBC MDA levels. The decreased antioxidant enzymes did not improve through exercise only. However, the decreased vitamins, and increased MDA, glucose levels and white blood cell (WBC) counts were improved either by exercise or exercise plus VCE supplementation. There were no significant changes in the RBC counts and hemoglobin values in the five groups.

In conclusion, these data demonstrate that there is an increase in MDA in the blood of diabetic pregnant animals, whereas there is a decrease in the number of fetuses, antioxidant vitamins and enzymes. However, dietary VCE with moderate exercise may strengthen the antioxidant defense system due to reducing ROS. They may play a role in preventing diabetes-related diseases of pregnant subjects.
An International Standard for whole blood folate: evaluation of a lyophilised haemolysate in an international collaborative study
Authors: Thorpe Susan J. , Sands Dawn , Heath Alan B. , Hamilton Malcolm S. , Blackmore Sheena , Barrowcliffe Trevor
Published: August 2004

Folate measurements, particularly for whole blood, show wide inter-laboratory and inter-methodology variability. This variability appears to be due in part to the lack of internationally accepted reference materials. A whole blood haemolysate, lyophilised in ampoules and designated 95/528, was therefore evaluated by 15 laboratories in five countries for its suitability as an International Standard (IS) for whole blood folate. The preparation was assayed using a variety of microbiological and protein-binding methodologies against local standards and calibrators. A consensus folate content was assigned to 95/528. The inclusion of three whole blood samples in the study with widely differing folate levels demonstrated a considerable reduction in inter-laboratory variability when the folate content of the samples was determined relative to the proposed IS 95/528 rather than to laboratories' local standards and calibrators. Accelerated degradation studies indicated that the folate content of 95/528 is stable when stored at −20°C. On the basis of the results presented here, the World Health Organization Expert Committee on Biological Standardization established 95/528 as an IS for whole blood folate.
Population-specific reference values for thyroid hormones on the Abbott ARCHITECT i2000 analyzer
Authors: González-Sagrado Manuel , Martín-Gil Francisco Javier
Published: August 2004

Reliable reference ranges are important in the interpretation of laboratory data, and it is incumbent on each laboratory to verify that the ranges they use are appropriate for the patient population they serve. The objective of this study was to determine population-specific reference ranges for thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and total triiodothyronine (TT3) on the Abbott ARCHITECT
Pitfalls and drawbacks in screening of congenital disorders of glycosylation
Authors: Marklová Eliška , Albahri Ziad
Published: August 2004

Congenital disorders of glycosylation include a group of diseases, each of them caused by different protein (mostly enzyme) impairment due to a specific gene defect. The many subtypes are classified according to clinical features, enzymology and molecular genetic analyses. Problems in diagnostics arise from the great diversity in clinical presentation, usually age-related, and different severities of individual types of these, by far underdiagnosed, diseases. Also the biochemical findings tend to vary, even within a single type. No one screening test, common for all types, is available so far. Several methods of choice may be used in the first approach; other procedures must follow for detailed typing of the defect. Possible drawbacks and pitfalls in the diagnostics from the viewpoint of our 3-year studies and practical screening experience are presented.
Rapid generation of detailed loss of heterozygosity profiles for routine diagnosis of gliomas
Authors: Beetz Christian , Hartmann Armin , Kiehntopf Michael , Wölfl Stefan , Kalff Rolf , Deufel Thomas , Patt Stephan
Published: August 2004

Aberrations in the genomes of gliomas seem to correlate well with clinical parameters. Pertinent studies, however, rely on highly sophisticated methods, they require large amounts of high-quality sample material and/or they demand profound analytical expertise. Consequently, molecular tumour analysis has not yet been widely implemented in routine laboratory applications. We have developed an easy-to-perform approach for the rapid derivation of a detailed lossof-heterozygosity profile from individual gliomas. DNA of PCR quality is extracted in a one-step procedure from routinely obtained material. A microsatellite-based marker set is used to detect the deletion status of genomic regions (i) with established diagnostic relevance, (ii) recurrently found deleted in gliomas, or (iii) generally associated with tumour suppressor activity. The complete profile comprises 25 regions and is generated from 64 markers multiplexed into 18 reactions. Illustratively, we present findings from an anaplastic oligodendroglioma; the molecular data for this tumour allow refined diagnostic and prognostic statements that could not be derived from histology alone. Our approach should prove useful in the routine diagnosis of gliomas. Simultaneously, research data for many highly relevant regions are generated in a comparatively simple and inexpensive way.
Urine labeling with orally applied marker substances in drug substitution therapy
Authors: Huppertz Bernd , Gauchel Gisela , Feiertag Heribert , Schweizer Hermann , Krieger Horst , Richter Francois , Heinz Helmut , Blanke Joerg , Gastpar Markus , Keller Ruprecht
Published: August 2004

The compliance of 581 drug addicts attending six methadone substitution outpatient clinics was determined over a period of 18 months. Urine from these patients was labeled following oral administration of low molecular weight polyethylene glycols as marker substances. These substances were measured in approx. 5800 urine samples. A protocol for applying marker substances and ways to prevent substitution of urine samples were evaluated. Normal values for marker substances in urine were determined. The results suggest that this labeling procedure is a new diagnostictool to prevent manipulation of urine samples by drug addicts receiving substitution therapy.
Cardiac natriuretic hormones, neuro-hormones, thyroid hormones and cytokines in normal subjects and patients with heart failure
Authors: Emdin Michele , Passino Claudio , Prontera Concetta , Iervasi Annalisa , Ripoli Andrea , Masini Silvano , Zucchelli Gian Carlo , Clerico Aldo
Published: August 2004

The derangement of neuro-endocrine control of circulation influences both disease evolution and response to treatment in patients with heart failure, but little data are available about the complex relationships between the degree of neuro-hormonal activation and clinical severity. We studied the relationships between cardiac natriuretic hormones (CNHs) and several neuro-hormones and immunological markers in a prospective cohort of 105 consecutive patients with cardiomyopathy (77 men and 28 women, mean age 66.7±12.4 years, range 33–89 years). We assayed the circulating levels of CNHs (atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)), plasma renin activity (PRA), aldosterone, cortisol, adrenaline, noradrenaline, thyroid hormones and thyroid stimulating hormone (TSH), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The concentrations of all CNHs and neuro-hormones were higher in patients with heart failure compared to normal subjects, except for free triiodothyronine (FT3), which was below normal values. ANP was positively related to NYHA class, IL-6, adrenaline, noradrenaline and cortisol, while negatively with ejection fraction and FT3. BNP was positively related to age, NYHA class, IL-6, TNF-α, adrenaline, noradrenaline and cortisol, while negatively with ejection fraction and FT3. A stepwise multiple linear regression indicated that plasma ANP depended only on ejection fraction, adrenaline and noradrenaline values, while for plasma BNP variation NYHA class contributed too. Our data confirm a progressive activation of hormonal and immunological systems in patients with heart failure. Furthermore, CNH circulating levels in heart failure are affected not only by cardiac function and disease severity, but also by activation of neuro-hormonal and stress-related cytokine systems, as well as by the thyroid hormones, even on usual medical treatment.
Clinical utility of serum holotranscobalamin as a marker of cobalamin status in elderly patients with neuropsychiatric symptoms
Authors: Nilsson Karin , Isaksson Anders , Gustafson Lars , Hultberg Björn
Published: August 2004

Early diagnosis of cobalamin deficiency is crucial, owing to the latent nature of this disorder and the resulting possible irreversible neurological damage. A normal serum cobalamin concentration does not reliably rule out a functional cobalamin deficiency and there does not at present seem to be any single diagnostic approach to achieve this diagnosis. A new marker for cobalamin status is the serum concentration of cobalamin bound to transcobalamin II (holoTC). Because methods suitable for routine use have been unavailable until recently, the clinical value of lowholoTC is still uncertain. Furthermore, there is at the moment no gold standard or true reference method to diagnose subtle cobalamin deficiency, which makes evaluation of the clinical usefulness of holoTC and the estimation of sensitivity and specificity problematic. In this study, we aimed to assess whether low holoTC concentrations are congruent with other biochemical signs of cobalamin deficiency in a group of psychogeriatric patients. The findings in the present study showthat holoTC is strongly related to serum cobalamin (0.68; p<0.001 in both patients and controls). Distribution of the different markers for cobalamin/folate status in the 33 patients with low levels of serum holoTC (below40 pmol/l) showed that 17 patients had normal levels of the other markers for cobalamin status. This may indicate poor specificity of lowholoTC for cobalamin deficiency. In 23 out of 176 patients with normal levels of holoTC we observed pathological levels of other markers for cobalamin deficiency. The use of holoTC in the present study group did not give significant additional information other than that given by serum cobalamin and therefore cannot be recommended in this clinical setting.
Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3)
Authors: Elmlinger Martin W. , Kühnel Werner , Weber Matthias M. , Ranke Michael B.
Published: August 2004

Assays for insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) have become essential tools in the diagnostic work-up of disorders of the somatotropic axis in children and adults. The aim of this study was to evaluate the automated IMMULITE
First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay – Lp(a) SRM 2B
Authors: Dati Francesco , Tate Jillian R. , Marcovina Santica M. , Steinmetz Armin
Published: August 2004

Lipoprotein(a) is an important predictor of cardiovascular disease risk. The lack of internationally accepted standardization has impeded the broad application of this lipoprotein in laboratory medicine. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), through its Working Group on Lipoprotein(a) and together with research institutions and several diagnostic companies, have succeeded in developing an international reference material that is intended for the transfer of a lipoprotein(a) concentration to manufacturers' master calibrators. IFCC SRM 2B has recently been accepted by the WHO Expert Committee on Biological Standardization as the ‘First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay’. The assigned unitage of 0.1071 nanomoles of lipoprotein(a) per vial is traceable to the consensus reference method for lipoprotein( a) and will enable conformity by diagnostic companies to the European Union's Directive on In vitro Diagnostic Medical Devices for the metrological traceability of calibrator materials.
Selecting clinically relevant populations for reference intervals
Authors: Ritchie Robert F. , Palomaki Glenn
Published: August 2004

The selection of individuals to represent a group for any purpose can commit the effort to success or failure from the very outset. The description of this group must reflect what is, in reality, the purpose for which the group is being studied. Considering that reference intervals are designed to assist clinicians during diagnostic triage, criteria must reflect the nature of the subjects entering the system for care. The majority of people seeking care have non-life-threatening, yet troublesome complaints. In other words, persons who are in a

Compounding this awkward situation has been the conviction that by increasing laboratory precision and accuracy, the utility of laboratory data, reference intervals in particular, will improve clinical understanding. This has, after many years, not proven to be the case. What has become very evident, however, is that unsustainably large sums of money are being devoted to improving laboratory performance. To what end, when we are unable to grasp the significance of what is available now including published reference intervals for common test values?

A realistic perspective on the value of prevailing laboratory performance, as illustrated by reference intervals, must be adopted. The obligation of laboratories, its regulators and professional groups is to create a sustainable mechanism to provide clinically usable information, in a timely and affordable manner, to our population and to those legions of less fortunate humans.