bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Analysis of Tyrosine Hydroxylase mRNA for Sensitive Detection of Neuroblastoma Cells in Blood and Bone Marrow
Authors: Träger Catarina , Kogner Per , Lindskog Magnus , Ponthan Frida , Kullman Anita , Kågedal Bertil 
Published: February 2004

AbstractBackground: Sensitive monitoring of minimal residual disease may improve the treatment of neuroblastoma in children. To detect and monitor neuroblastoma cells in blood and bone marrow, we developed a quantitative method for the analysis of tyrosine hydroxylase mRNA.Methods: We used real-time reverse transcription-PCR. The calibrator was constructed from a segment of tyrosine hydroxylase mRNA that included the target. Blood and bone marrow samples from 24 children with neuroblastoma and 1 child with ganglioneuroma were analyzed. Controls were blood samples from the cords of 40 babies, from 58 children 6 months to 15 years of age, and from 34 healthy adults, as well as from 12 children with other diseases.Results: The detection limit was ∼70 transcripts/mL. All 144 blood controls were below this limit. At diagnosis, blood tyrosine hydroxylase mRNA was higher in children with widespread disease (stage 4/4S; n = 6; range, 203–46 000 transcripts/mL) than in patients with localized disease (stages 1–3; n = 6; ≤83 transcripts/mL; P = 0.002). Bone marrow from all five children with localized disease had concentrations &lt;72 transcripts/mL, whereas five of six stage 4 patients had increased concentrations (6000–8 000 000 transcripts/mL; P &lt;0.05). In nine children in whom tyrosine hydroxylase mRNA was measured repeatedly, the results corresponded to the clinical course.Conclusion: Quantitative analysis of tyrosine hydroxylase mRNA in blood and bone marrow is reliable and easy to perform and may be used for upfront staging, prognostic assessment, and treatment monitoring of neuroblastoma.
Predictors of Change in Plasma Total Cysteine: Longitudinal Findings from the Hordaland Homocysteine Study
Authors: El-Khairy Lina , Vollset Stein E , Refsum Helga , Ueland Per M 
Published: February 2004

Abstract
Background: Total cysteine (tCys) in plasma has recently been linked to cardiovascular risk and is also associated with cardiovascular risk factors, including body mass index (BMI) and cholesterol. Changes and predictors of change in tCys concentrations over a mean follow-up time of 6.0 (5.2–7.2) years were assessed in this study.
Methods: Baseline data from the Hordaland Homocysteine Study recorded in 1992–1993 included tCys, total homocysteine (tHcy), and various lifestyle and cardiovascular risk factors. In 1998–1999, the same measurements were repeated in 3732 individuals born in 1950–1951 and 3339 individuals born in 1925–1927. Most of the statistical analyses were done separately in the four age and sex groups.
Results: The overall mean values of tCys were higher at follow-up [mean (SD), 296 (41) μmol/L] than at baseline [278 (36.5) μmol/L]; P &lt;0.0001. The mean percentage of increase in tCys in the different age and sex groups ranged from 4.9% to 8.5%. There was a significant correlation between the tCys values measured on the two occasions (Spearman correlation coefficient, 0.55–0.59 in the different age and sex groups; P &lt;0.0001). The change in tCys correlated with changes in BMI, cholesterol, and diastolic blood pressure in the younger age group, whereas only changes in BMI predicted changes in tCys in the older age group.
Conclusions: tCys increased in the 6 years between the two measurements. Factors related to the baseline tCys values, including BMI and the change in BMI, predicted the tCys changes over time.
Prevalence of Fatty Acid Ethyl Esters in Meconium Specimens
Authors: Moore Christine , Jones Joseph , Lewis Douglas , Buchi Karen 
Published: February 2004

AbstractBackground: Fetal alcohol syndrome (FAS), alcohol-related birth defects (ARBDs), and alcohol-related neurodevelopment disorders (ARNDs) in neonates are often the result of maternal alcohol consumption during pregnancy. Facial characteristics are associated with FAS, but ARBDs and ARNDs are more difficult to diagnose. Fetal exposure to alcohol can cause central nervous system dysfunction, pre- and postnatal growth problems, cardiac defects in neonates, and attention deficit disorders and mental retardation in older children. To date, diagnosis of fetal alcohol effect has depended largely on maternal interview, although clinical tests are becoming more widely used. Fatty acid ethyl esters (FAEEs) are formed in the body by esterification of ethanol with free fatty acids and trans-esterification of glycerides and have been detected in the meconium of newborns. This report estimates the prevalence of fetal alcohol exposure in two populations by detecting FAEEs in meconium.Methods: We analyzed the prevalence of FAEEs in the meconium of two separate groups of neonates by use of solid-phase extraction and analysis by gas chromatography–mass spectrometry in the chemical ionization mode. In the first study, meconium samples were taken anonymously from babies born in a large, regional perinatal center in Hawaii. In the second study, specimens were obtained from infants admitted to six different newborn intensive care units within the state of Utah.Results: In the first study, 73 of 436 (16.7%) meconium specimens tested were considered positive for FAEEs. When broken down into quartiles, the mean total FAEEs measured were 1059, 3133, 6628, and 62115 ng/g. In the second study, 35 of 289 (12.1%) specimens were considered positive. When broken into quartiles, the mean total FAEEs were 1139, 3067, 7674, and 50 143 ng/g. The overall FAEE profiles of the two study sets were remarkably similar.Conclusion: In an adequate meconium specimen, a total FAEE concentration &gt;10 000 ng/g may indicate that the newborn has been exposed to significant amounts of alcohol during pregnancy.
Hemoglobin Görwihl [α2β25(A2)Pro→Ala], an Electrophoretically Silent Variant with Impaired Glycation
Authors: Bissé Emmanuel , Schauber Claude , Zorn Nathalie , Epting Thomas , Eigel Antonin , Van Dorsselaer Alain , Wieland Heinrich , Kister Jean , Kiger Laurent 
Published: February 2004

AbstractBackground: Some of the genetic variants of hemoglobin (Hb) and their chemically modified species are known to affect the measurement of Hb A1c. The purpose of this study was to characterize Hb species in the blood sample of a 74-year-old German male with an exceptionally low Hb A1c value.Methods: Hemolysates from the propositus and a healthy individual were analyzed by electrophoresis, cation-exchange HPLC, boronate affinity chromatography, and electrospray ionization-mass spectrometry (ESMS). Genomic DNA was amplified by PCR, and the sequencing was performed on an ABI 310 sequencer. Functional properties of Hb were determined by oxygen equilibrium studies and CO recombination kinetics after flash photodissociation. Glycohemoglobin species were synthesized by incubating hemolysates with glucose.Results: A novel, electrophoretically silent β chain, β5(A2)Pro→Ala or Hb Görwihl, was detected by cation-exchange HPLC. It accounted for ∼44% of the total Hb and had functional properties similar to those of normal Hb A and a mild degree of heat instability. During incubation with glucose, glycation of the β chains (assessed by ESMS) in the hemolysate of a healthy volunteer was twice as fast as in hemolysate from the propositus.Conclusions: The substitution β5(A2)Pro→Ala seems to affect neither the functional properties nor the heterotropic interactions of Hb, but slows glycation of the N-terminal valine by an unknown mechanism.
Plasma Vitamin B6 Vitamers before and after Oral Vitamin B6 Treatment: A Randomized Placebo-controlled Study
Authors: Bor Mustafa Vakur , Refsum Helga , Bisp Marianne R , Bleie Øyvind , Schneede Jorn , Nordrehaug Jan Erik , Ueland Per Magne , Nygard Ottar Kjell , Nexø Ebba 
Published: February 2004

Abstract
Background: Vitamin B6 has attracted renewed interest because of its role in homocysteine metabolism and its possible relation to cardiovascular risk. We examined the plasma B6 vitamers, pyridoxal 5′-phosphate (PLP), pyridoxal (PL), pyridoxine (PN), and 4-pyridoxic acid (4-PA) before and after vitamin B6 supplementation.
Methods: Patients (n = 90; age range, 38–80 years) undergoing coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial) were allocated to the following daily oral treatment groups: (A), vitamin B12 (0.4 mg), folic acid (0.8 mg), and vitamin B6 (40 mg); (B), vitamin B12 and folic acid; (C), vitamin B6; or (D), placebo. EDTA blood was obtained before treatment and 3, 14, 28, and 84 days thereafter.
Results: Before treatment, PLP (range, 5–111 nmol/L) and 4-PA (6–93 nmol/L) were the predominant B6 vitamers identified in plasma. During the 84-day study period, the intraindividual variation (CV) in patients not treated with vitamin B6 (groups B and D) was 45% for PLP and 67% for 4-PA. Three days after the start of treatment, the increases in concentration were ∼10-, 50-, and 100-fold for PLP, 4-PA, and PL, respectively. No significant additional increase was observed at the later time points. The PLP concentration correlated to the concentrations of 4-PA and PL before treatment, but not after treatment. The PL concentration correlated with 4-PA before and after treatment.
Conclusions: Vitamin B6 treatment has an immediate effect on the concentrations and the forms of B6 vitamers present in plasma, and the changes remain the same during prolonged treatment. Our results suggest that the B6 vitamers in plasma reflect vitamin B6 intake.
Use of a Major Medical Center Clinical Laboratory as a Reference Laboratory for a Developing Country: Ordering Patterns Help Set Laboratory Priorities
Authors: Ladenson Jack H , Scott Mitchell G , Klarkowski Derryck , Seyoum Melles 
Published: February 2004

Abstract
Background: The test menus for developed and developing countries may differ, depending on many factors, including the expected volume of testing, disease frequency and therapies available, clinical impact of the test, technical skill and equipment needed, cost, the patient population served, and whether alternative testing sites are available, and some of them may not be exactly known. We assessed test priorities in a developing country by making a broad range of tests available and then assessing which tests were actually used by the physicians in the country for the care of their patients.
Methods: The Barnes-Jewish Hospital laboratory and Washington University Medical Center provided patients in the developing country of Eritrea access to the same tests as patients in St. Louis for all analytes that are stable at 4 °C, the lowest temperature that could be used for shipping.
Results: The use of the St. Louis laboratories increased steadily from 1998 to 2001. More than one-half of the physicians in Eritrea used the reference laboratories, with requests for thyroid function and female fertility representing 48–71% of the test requests over the 4 years evaluated. The high degree of utilization for these test batteries was not predicted. Testing for thyroid function, female fertility, and lipid panels are now performed, or soon will be performed, in Eritrea based on the experience of the reference laboratory system. The reference laboratory system is continuing so that the test priorities of the country can be evaluated on an ongoing basis and specialized tests can be made available at a low cost.
Conclusion: The experiences of a reference laboratory for a developing country can help to identify unanticipated priorities for medical testing within the country.
Use of High-Throughput DNA Microarrays to Identify Biomarkers for Bladder Cancer
Authors: Sánchez-Carbayo Marta 
Published: February 2004

Abstract
Background: Numerous markers have been described to correlate to some extent with tumor stage and prognosis of patients with bladder cancer. The power of many of these biomarkers in detecting superficial disease or predicting the clinical outcome of individual tumors is limited, and alternative markers are still in demand. High-throughput microarrays represent novel means for cancer research and tumor marker discovery.
Approach: The aim of this report was to discuss the application of DNA technologies to provide novel biomarkers for bladder cancer.
Content: Specific bladder tumor subtypes have distinct gene expression profiles. The use of high-throughput DNA microarrays allows identification of the most prevalent and relevant alterations within bladder tumors. Clusters of differentially expressed genes will become biomarkers to discriminate subgroups of patients with different histopathology or clinical outcome. Additionally, the identified individual molecular targets might be further validated and developed into novel serum or urinary biomarkers for the diagnosis and/or as prognostic factors to be applied in clinical practice. The diagnosis and prognosis of bladder cancer would be enhanced by the use of such markers, and the marker itself may constitute a therapeutic target when studied in appropriate patients and control groups.
Summary: Expression profiling with high-throughput DNA microarrays has the potential of providing critical clues for the management of bladder cancer patients. As the quality, standardization, and ease of use of the technology increase and the costs decrease, DNA microarrays will move from being a technology restricted to research to clinical laboratories in the near future.
Angiogenesis Assays: A Critical Overview
Authors: Auerbach Robert , Lewis Rachel , Shinners Brenda , Kubai Louis , Akhtar Nasim 
Published: February 2004

Abstract
Background: Angiogenesis, the formation of new blood vessels, is an integral part of both normal developmental processes and numerous pathologies, ranging from tumor growth and metastasis to inflammation and ocular disease. Angiogenesis assays are used to test efficacy of both pro- and antiangiogenic agents.
Methods: Most studies of angiogenesis inducers and inhibitors rely on various models, both in vitro and in vivo, as indicators of efficacy. In this report we describe the principal methods now in use: the in vivo Matrigel plug and corneal neovascularization assays, the in vivo/in vitro chick chorioallantoic membrane (CAM) assay, and the in vitro cellular (proliferation, migration, tube formation) and organotypic (aortic ring) assays. We include description of two new methods, the chick aortic arch and the Matrigel sponge assays.
Conclusions: In vitro tests are valuable, can be carried out expeditiously, and lend themselves to quantification, but must be interpreted with extreme caution. In vitro tests are best viewed as providing initial information, subject to confirmation by in vivo assays. Multiple tests should be used to obtain maximum benefit from in vitro tests. In vivo tests are more difficult and time-consuming to perform, thereby limiting the number of tests that can run at any one time. Quantification is generally more difficult as well. However, in vivo assays are essential because of the complex nature of vascular responses to test reagents, responses that no in vitro model can fully achieve.
Windows to the Ward: Graphically Oriented Report Forms. Presentation of Complex, Interrelated Laboratory Data for Electrophoresis/Immunofixation, Cerebrospinal Fluid, and Urinary Protein Profiles
Authors: Regeniter Axel , Steiger Jürg U , Scholer André , Huber Peter R , Siede Werner H 
Published: February 2004

AbstractBackground: Automated laboratory analyzers that mass produce data have been linked to information systems for more than two decades, but little progress has been made in developing more comprehensible report forms. Results are still reported in computer-generated printouts containing hundreds of numbers crowded into columns on each printed page.Methods: We developed three software applications focusing on the graphic presentation of laboratory results.Results: The first application summarizes data for a patient with a monoclonal gammopathy. The report provides a cumulative graphic presentation of immunofixation/electrophoresis data without any additional interpretation, focuses on a color-coded electrophoresis scan, and records up to 5 years on a single page. The second application deals with cerebrospinal fluid analysis. The report calculates relevant data and graphs the complex relationship between albumin and immunoglobulin results from paired serum and cerebrospinal fluid samples. Manually added interpretive text assures an output comprehensible to clinicians in all specialties. The third application produces a report summarizing quantitatively measured urinary marker protein profiles. The report form is generated by a flexible, completely user-definable knowledge-based system. It calculates numerous ratios and formulae, supports reflex testing, supplies an automated interpretation, and generates a specific graphic signature pattern of the results (MDI LabLink proteinuria differentiation).Conclusions: Increased clinical demand for graphically oriented report forms 5 years after their introduction has provided evidence that these reports transfer complex laboratory data and results to the clinician more effectively. The highest (more than threefold) increase in demand has been for reports for urinary marker protein profiles that feature a largely self-explanatory graphic signature pattern.
Quantitative Real-Time PCR Method for Detection of B-Lymphocyte Monoclonality by Comparison of κ and λ Immunoglobulin Light Chain Expression
Authors: Ståhlberg Anders , Åman Pierre , Ridell Börje , Mostad Petter , Kubista Mikael 
Published: February 2004

AbstractBackground: An abnormal IgLκ:IgLλ ratio has long been used as a clinical criterion for non-Hodgkin B-cell lymphomas. As a first step toward a quantitative real-time PCR-based multimarker diagnostic analysis of lymphomas, we have developed a method for determination of IgLκ:IgLλ ratio in clinical samples.Methods: Light-up probe-based real-time PCR was used to quantify IgLκ and IgLλ cDNA from 32 clinical samples. The samples were also investigated by routine immunohistochemical analysis and flow cytometry.Results: Of 32 suspected non-Hodgkin lymphoma samples analyzed, 28 were correctly assigned from real-time PCR measurements assuming invariant PCR efficiencies in the biological samples. Four samples were false negatives. One was a T-cell lymphoma, one was a diffuse large B-cell lymphoma, and one was reanalyzed and found lymphoma-positive by in situ calibration, which takes into account sample-specific PCR inhibition. Twelve of the samples were fine-needle aspirates, and these were all correctly assigned.Conclusions: This work is a first step toward analyzing clinical samples by quantitative light-up probe-based real-time PCR. Quantitative real-time PCR appears suitable for high-throughput testing of cancers by measuring expression of tumor markers in fine-needle aspirates.
C-Reactive Protein, Interleukin-6, and Procalcitonin in the Immediate Postnatal Period: Influence of Illness Severity, Risk Status, Antenatal and Perinatal Complications, and Infection
Authors: Chiesa Claudio , Pellegrini Gabriella , Panero Alessandra , Osborn John F , Signore Fabrizio , Assumma Marcello , Pacifico Lucia 
Published: February 2004

AbstractBackground: Studies of the diagnostic accuracy of most laboratory tests for early-onset neonatal sepsis have yielded variable results. We investigated whether some of this variation might be attributable to differences in population baseline severity and risk status as well as to specific ante- and perinatal variables, independent of the presence of neonatal infection.Methods: The Score for Neonatal Acute Physiology (SNAP) was used to define illness severity, with SNAP Perinatal Extension (SNAP-PE) used to define the combined physiologic and perinatal mortality risk. A total of 134 ill newborns (19 with early-onset infection and 115 with no infection) were available for simultaneous analysis of the association of SNAP, SNAP-PE, and maternal and perinatal variables with C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) concentrations at birth and at 24 and 48 h of life.Results: Early-onset neonatal infection was associated with significant increases in CRP, IL-6, and PCT concentrations at all three time points, independent of illness severity. However, among babies without infection, higher SNAP and SNAP-PE scores were associated with higher IL-6 concentrations at birth. Certain maternal or perinatal variables altered IL-6 and PCT values in the infected as well as in the uninfected neonates. However, if different cutoff points were used at any of the three neonatal ages, PCT sensitivity and specificity were greater than those of CRP or IL-6.Conclusions: Illness severity and risk status are unlikely to interfere with the use of CRP and PCT for detection of early-onset neonatal sepsis. In contrast, the diagnostic value of IL-6 at birth may be altered by physiologic severity and risk indexes. The reliability of CRP, IL-6, and PCT for the diagnosis of early-onset neonatal infection requires specific cutoff values for each evaluation time point over the first 48 h of life.
Outcome Validation of the Beckman Coulter Access Analyzer in a Second-Trimester Down Syndrome Serum Screening Application
Authors: MacRae Andrew R , Gardner H Allen , Allen Lynn C , Tokmakejian Sonya , Lepage Nathalie 
Published: February 2004

Abstract
Background: Mid-trimester maternal serum α-fetoprotein (AFP) and unconjugated estriol (uE3) are 30% lower and human chorionic gonadotropin (hCG) is twofold higher in Down syndrome pregnancies compared with unaffected pregnancies. In maternal serum screening, patient-specific risks are calculated using published gaussian frequency distribution parameters for these three markers obtained with previously available immunoassays. New immunoassays must generate similar distribution parameters if the accuracy of assigned risks and overall performance of prenatal screening are to be maintained.
Methods: Agreement between the Beckman Coulter Access and the Bayer Immuno 1 assays for AFP and hCG and the Amersham Amerlex-M RIA for uE3 was assessed in 558 fresh sera. Precision was measured over 6 weeks. Median concentrations were calculated by regression of 568 Caucasian singleton pregnancy samples against gestational age in days. Frozen mid-trimester sera from 44 confirmed Down syndrome singleton pregnancies (cases) were selected without conscious bias for reanalysis, and each case was matched with five control specimens from unaffected pregnancies. Serum markers were expressed as the multiple of the median (MoM) concentration derived from the control samples, cor-rected for maternal weight and converted to their log-equivalent values. Normality was assessed using probability plots and the Shapiro–Wilk W-test. Gaussian distribution parameters were compared with established values, and Down syndrome risk calculations were assessed with a commonly used risk algorithm.
Results: The Access AFP and hCG assays had consistent proportional agreement with the established assays, whereas agreement between the uE3 methods was less consistent. Analytical imprecision was 3–6% at mid-trimester concentrations. Normal distributions were obtained for the log MoM values of all three markers in both the Down syndrome and unaffected populations, and their gaussian distribution parameters compared well with established values. The performance of the Access assays in an established trivariate risk algorithm for Down syndrome was equal to the performance exhibited by traditional methods.
Conclusion: The Beckman Coulter Access analyzer provides valid mid-trimester serum AFP, uE3, and hCG results and risk assessments when applied in a prenatal Down syndrome screening service.