bluuebunny/crossref_metadata_2025_split huggingface dataset:
Butyrylcholinesterase (BCHE) Genotyping for Post-Succinylcholine Apnea in an Australian Population
Authors: Yen Tina , Nightingale Brian N , Burns Jennifer C , Sullivan David R , Stewart Peter M 
Published: February 2004

Abstract
Background: Measurement of plasma butyrylcholinesterase (BChE) activity and inhibitor-based phenotyping are standard methods for identifying patients who experience post-succinylcholine (SC) apnea attributable to inherited variants of the BChE enzyme. Our aim was to develop PCR-based assays for BCHE mutation detection and implement them for routine diagnostic use at a university teaching hospital.
Methods: Between 1999 and 2002, we genotyped 65 patients referred after prolonged post-SC apnea. Five BCHE gene mutations were analyzed. Competitive oligo-priming (COP)-PCR was used for flu-1, flu-2, and K-variant and direct DNA sequencing analysis for dibucaine and sil-1 mutations. Additional DNA sequencing of BCHE coding regions was provided when the five-mutation screen was negative or mutation findings were inconsistent with enzyme activity.
Results: Genotyping identified 52 patients with primary hypocholinesterasemia attributable to BCHE mutations, and in 44 individuals the abnormalities were detected by the five-mutation screen (detection rate, 85%). Additional sequencing studies revealed mutations in eight other patients, including five with novel mutations. The most common genotype abnormality was compound homozygous dibucaine and homozygous K-variant mutations. No simple homozygotes were found. Of the remaining 13 patients, 3 had normal BChE activity and gene, and 10 were diagnosed with hypocholinesterasemia unrelated to BCHE gene abnormalities.
Conclusion: A five-mutation screen for investigation of post-SC apnea identified BCHE gene abnormalities for 80% of a referral population. Six new BCHE mutations were identified by sequencing studies of 16 additional patients.
Plasma 99th Percentile Reference Limits for Cardiac Troponin and Creatine Kinase MB Mass for Use with European Society of Cardiology/American College of Cardiology Consensus Recommendations
Authors: Apple Fred S , Quist Heidi E , Doyle Patrick J , Otto Angela P , Murakami MaryAnn M 
Published: February 2004

AbstractBackground: The European Society of Cardiology/American College of Cardiology (ESC/ACC) consensus document for definition of myocardial infarction (MI) is predicated on increased cardiac troponin or creatine kinase (CK) MB mass above the 99th percentile reference limit. The purpose of this study was to determine the plasma (heparin) 99th percentile reference limits for the leading in vitro diagnostic cardiac troponin and CKMB mass assays.Methods: Blood (heparin plasma) was obtained from healthy adults (n = 696; age range, 18–84 years) stratified by gender and ethnicity. Cardiac troponin I (cTnI) and T (cTnT) and CKMB mass concentrations were measured by eight assays. Reference limits were determined by nonparametric statistical analysis.Results: Two cTnI assays demonstrated at least a 1.2- to 2.5-fold higher 99th percentile for males vs females, with the mean concentrations significantly higher for males (P &lt;0.05). Two cTnI assays also demonstrated a 1.1- to 2.8-fold higher 99th percentile for blacks vs Caucasians, with the mean concentrations significantly higher for blacks (P = 0.05). There was a 13-fold variance between the lowest measured 99th percentile (0.06 μg/L) and the highest (0.8 μg/L). All CKMB assays demonstrated a 1.2- to 2.6-fold higher 99th percentile for males vs females, with mean concentrations significantly higher for males (P &lt;0.0001). Four CKMB assays also showed significantly higher (1.2- to 2.7-fold) mean concentrations for blacks (P &lt;0.02) vs Caucasians.Conclusions: The heparin-plasma 99th percentile reference limits for cardiac troponin and CKMB mass provide an evidence base in support of the ESC, ACC, and American Heart Association guidelines for detection of myocardial injury. Selective gender and ethnic differences were demonstrated. These data allow clinicians, trialists, and epidemiologists a common point for operational use.
Utility of the Amino-Terminal Fragment of Pro-Brain Natriuretic Peptide in Plasma for the Evaluation of Cardiac Dysfunction in Elderly Patients in Primary Health Care
Authors: Alehagen Urban , Lindstedt Göran , Eriksson Henry , Dahlström Ulf 
Published: February 2004

AbstractBackground: The aims of this study were to measure the N-terminal fragment of pro-brain natriuretic peptide (proBNP) in plasma in medical conditions commonly found in primary care and to evaluate the utility of these measurements in identifying impaired cardiac function in elderly patients with symptoms associated with heart failure.Methods: We studied 415 patients (221 men and 194 women; mean age, 72 years) who had contacted a primary healthcare center for dyspnea, fatigue, and/or peripheral edema. One cardiologist evaluated the patients in terms of history, physical examination, functional capacity, electrocardiography, and suspicion of heart failure. Plasma N-terminal proBNP was measured by an in-house RIA. An ejection fraction ≤40% by Doppler echocardiography was regarded as reduced cardiac function. Abnormal diastolic function was defined as an abnormal mitral inflow defined as reduced ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio), or as abnormal pulmonary venous flow pattern.Results: Patients with impaired functional capacity, impaired systolic function, and/or impaired renal function had significantly increased N-terminal proBNP concentrations. By multiple regression analysis, N-terminal proBNP concentrations were also influenced by ischemic heart disease, cardiac enlargement, and certain medications but not by increased creatinine. No gender differences were observed. Patients with isolated diastolic dysfunction attributable to relaxation abnormali-ties had lower concentrations than those with normal cardiac function, whereas those with pseudonormal E/A ratios or restrictive filling patterns had higher concentrations.Conclusions: Plasma N-terminal proBNP concentrations increase as a result of impaired systolic function, age, impaired renal function, cardiac ischemia and enlargement, and certain medications. Values are high in diastolic dysfunction with pseudonormal patterns, but not in patients with relaxation abnormalities. An increase in plasma N-terminal proBNP might be an earlier sign of abnormal cardiac function than abnormalities identified by currently used echocardiographic measurements.
Xuezhikang Decreases Serum Lipoprotein(a) and C-reactive Protein Concentrations in Patients with Coronary Heart Disease
Authors: Liu Ling , Zhao Shui-Ping , Cheng Yan-Chun , Li Yu-Ling 
Published: February 2004

AbstractBackground: Increased serum lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (hsCRP) concentrations are independent risk factors for coronary heart disease (CHD). Xuezhikang, an extract of cholestin, effectively lowers fasting cholesterol and triglyceride concentrations. We studied whether xuezhikang lowered Lp(a) and hsCRP concentrations.Methods: We randomly divided 60 CHD patients into two groups to receive xuezhikang (1200 mg daily) or placebo for 6 weeks. The fasting hsCRP concentration and the postprandial changes of serum lipid concentrations at 2, 4, and 6 h after a high-fat meal (800 calories; 50 g of fat) were measured before and after the 6-week protocol.Results: The two groups had similar baseline fasting lipid and hsCRP concentrations. The postprandial triglyceride and Lp(a) concentrations were significantly increased (P &lt;0.05). After 6 weeks, the fasting and postprandial lipid concentrations decreased significantly in the xuezhikang group, accompanied by a significant reduction in fasting hsCRP concentration (P &lt;0.001). The placebo group had no significant change in lipid concentrations, whereas the fasting serum hsCRP concentration was reduced significantly (P &lt;0.05). The reduction in hsCRP was closely related to the changes in fasting Lp(a) concentration (r = 0.402; P &lt;0.05) and triglyceride area under the curve (r = 0.441; P &lt;0.001).Conclusions: Xuezhikang effectively decreased fasting Lp(a) and postprandial triglyceride concentrations, which were associated with reductions of fasting hsCRP concentrations in CHD patients.
γ-Glutamyltransferase Is a Predictor of Incident Diabetes and Hypertension: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Lee Duk-Hee , Jacobs David R , Gross Myron , Kiefe Catarina I , Roseman Jeffrey , Lewis Cora E , Steffes Michael 
Published: February 2004

Abstract
Background: γ-Glutamyltransferase (GGT), which maintains cellular concentrations of glutathione, may be a marker of oxidative stress, and GGT itself may produce oxidative stress. We performed a prospective study to examine whether serum GGT predicts diabetes and hypertension.
Methods: Study participants were 4844 black and white men and women 18–30 years of age in 1985–1986; they were reexamined 2, 5, 7, 10, and 15 years later. Year 0 GGT cutpoints were 12, 17, 25, and 36 U/L (overall 25th, 50th, 75th, and 90th percentiles; the laboratory cutpoints for abnormal are 40 U/L in women and 50 U/L in men). We deleted 32 participants with prevalent diabetes and 140 participants with prevalent hypertension from the respective incidence analyses.
Results: After adjustment for study center, race, sex, and age in proportional hazards regression, the hazard ratios across year 0 GGT categories were 1.0, 1.6, 1.7, 4.0 (95% confidence interval, 2.0–8.1), and 5.5 (2.7–11.1) for 15-year incident diabetes and 1.0, 1.2, 1.7 (1.2–2.2), 2.3 (1.7–3.2), and 2.3 (1.7–3.2) for hypertension. Additional adjustment for year 0 alcohol consumption, body mass index, cigarette smoking, and physical activity attenuated this relationship, but GGT remained a significant predictor.
Conclusions: Serum GGT within a range regarded as physiologically normal is associated with incident diabetes and hypertension. Considering known functionality of GGT, these associations are consistent with a role for oxidative stress in risk for diabetes and hypertension.
Mild Transcobalamin I (Haptocorrin) Deficiency and Low Serum Cobalamin Concentrations
Authors: Carmel Ralph 
Published: February 2004

AbstractBackground: Low cobalamin concentrations are common, but their causes are often unknown. Transcobalamin I/haptocorrin (TC I/HC) deficiency, viewed as a rare cause, has not been examined systematically in patients with unexplained low serum cobalamin.Methods: Total TC I/HC was measured by RIA in three subgroups of 367, 160, and 38 patients with different categories of low cobalamin concentrations and three comparison subgroups of 112, 281, and 119 individuals with cobalamin concentrations within the reference interval. Additional studies, including family studies, were done in selected patients found to have low TC I/HC concentrations.Results: Low TC I/HC concentrations suggestive of mild TC I/HC deficiency occurred in 54 of 367 (15%) patients with low cobalamin identified by clinical laboratories and 24 of 160 (15%) patients whose low cobalamin was unexplained after absorption and metabolic evaluation, but in only 2 of 38 patients with malabsorptive causes of low cobalamin concentrations (5%). The prevalence was only 3% (8 of 281 plasma samples) to 5% (6 of 112 sera) in patients with cobalamin concentrations within the reference interval and 3% (4 of 119) in healthy volunteers. Three patients with low cobalamin (0.6%) had severe TC I/HC deficiency with undetectable TC I/HC. Presumptive heterozygotes for severe TC I/HC deficiency in two families had the findings of mild TC I/HC deficiency; mild deficiency was also found in at least three of seven studied families of patients with mild TC I/HC deficiency.Conclusions: Mild TC I/HC deficiency is frequently associated with low cobalamin, is often familial, and its biochemical phenotype appears identical to the heterozygous state of severe TC I/HC deficiency. Severe TC I/HC deficiency also appears to be more common than suspected. Both diagnoses should be considered in all patients with unexplained low serum cobalamin.
Testosterone Measured by 10 Immunoassays and by Isotope-Dilution Gas Chromatography–Mass Spectrometry in Sera from 116 Men, Women, and Children
Authors: Taieb Joëlle , Mathian Bruno , Millot Françoise , Patricot Marie-Claude , Mathieu Elisabeth , Queyrel Nicole , Lacroix Isabelle , Somma-Delpero Claude , Boudou Philippe 
Published: February 2004

AbstractBackground: Commercially available testosterone immunoassays give divergent results, especially at the low concentrations seen in women. We compared immunoassays and a nonimmunochemical method that could quantify low testosterone concentrations.Methods: We measured serum testosterone in 50 men, 55 women, and 11 children with use of eight nonisotopic immunoassays, two isotopic immunoassays, and isotope-dilution gas chromatography–mass spectrometry (ID/GC-MS).Results: Compared with ID/GC-MS, 7 of the 10 immunoassays tested overestimated testosterone concentrations in samples from women; mean immunoassay results were 46% above those obtained by ID/GC-MS. The immunoassays underestimated testosterone concentrations in samples from men, giving mean results 12% below those obtained by ID/GC-MS. In women, at concentrations of 0.6–7.2 nmol/L, 3 of the 10 immunoassays gave positive mean differences &gt;2.0 nmol/L (range, −0.7 to 3.3 nmol/L) compared with ID/GC-MS; in men at concentrations of 8.2–58 nmol/L, 3 of the 10 immunoassays tested gave mean differences &gt;4.0 nmol/L (range, −4.8 to 2.6 nmol/L).Conclusion: None of the immunoassays tested was sufficiently reliable for the investigation of sera from children and women, in whom very low (0.17 nmol/L) and low (&lt;1.7 nmol/L) testosterone concentrations are expected.
Indications for Requesting Laboratory Tests for Concurrent Diseases in Patients with Carpal Tunnel Syndrome: A Systematic Review
Authors: van Dijk Mariska A J , Reitsma Johannes B , Fischer Johan C , Sanders Gerard T B 
Published: February 2004

AbstractBackground: Carpal tunnel syndrome (CTS) is known as a repetitive motion disorder, but the role of other diseases in the development or prognosis of CTS is uncertain. We reviewed the literature to determine whether there is evidence for an increased prevalence of specific conditions in CTS patients and whether this evidence would support laboratory screening for these conditions.Methods: Medline, Embase, and Cochrane Controlled Trial Register were searched for key words related to CTS and associated diseases. Relevant articles were selected according to specific criteria. Sources of bias and heterogeneity attributable to differences in study design and in patient selection were investigated by subgroup analysis.Results: After an initial search, we limited ourselves to three potentially important conditions: diabetes mellitus (DM), hypothyroidism (HT), and rheumatoid arthritis (RA). We identified nine articles with a total of 4908 CTS patients and 7671 controls that met our selection criteria. The nine studies were heterogeneous with respect to clinical and methodologic factors. In general, the prevalence of concurrent diseases was higher in CTS patients than in controls: the pooled odds ratios were 2.2 (95% confidence interval, 1.5–3.1) for DM, 1.4 (1.0–2.0) for HT, and 2.2 (1.4–3.4) for RA. Studies of lower methodologic quality reported, on average, higher odds ratios. Only one study provided information about whether the diagnosis of the concurrent condition was already made at the time of the CTS diagnosis.Conclusions: We found evidence that the prevalences of DM, HT, and RA are higher in CTS patients, but only one study specifically addressed the issue of the prevalence of nonmanifest cases of the concurrent condition. At present, there is insufficient evidence for routine laboratory screening for concurrent conditions in all newly diagnosed CTS patients.
Detection of Chromosome 21-encoded mRNA of Placental Origin in Maternal Plasma
Authors: Oudejans Cees B M , Go Attie T J J , Visser Allerdien , Mulders Monique A M , Westerman Bart A , Blankenstein Marinus A , van Vugt John M G 
Published: February 2004

AbstractBackground: mRNA of placental origin (i.e., human placental lactogen and β-human chorionic gonadotropin) has been demonstrated to be easily detectable in maternal plasma. We tested whether detection of chromosome 21-encoded mRNA of placental origin is possible in maternal plasma obtained during the first trimester.Methods: Plasma samples were obtained from pregnant women between weeks 9–13 of pregnancy. RNA was isolated from 800 or 1600 μL of plasma by silica-based affinity isolation and, after on-column DNase treatment, was subjected to two-step, one-tube reverse transcription-PCR with gene specific primers.Results: Three chromosome 21-encoded genes located within the Down syndrome critical region with overexpression in trisomy 21 placentas were screened for expression in early placental tissue to select their potential use for RNA based plasma screening. One of the chromosome 21-encoded genes (LOC90625) showed strong expression in first trimester placenta similar to CSH1 (human placental lactogen) and was selected for plasma analysis. The RNA isolation assay was validated with CSH1 mRNA, which could be detected in the plasma of all women tested in weeks 9–13 of pregnancy. RNA from the chromosome 21-encoded, placentally expressed gene, LOC90625, was present in maternal first-trimester plasma and could be detected in 60% of maternal plasma samples when 800 μL of plasma was used and in 100% of samples when 1600 μL of plasma was used.Conclusion: The detection of chromosome 21-encoded mRNA of placental origin in maternal plasma during the first trimester may allow development of plasma-RNA-based strategies for prenatal prediction of Down syndrome. LOC90625 is a candidate gene for this purpose.
Prognostic Value of Multiple Reverse Transcription-PCR Tyrosinase Testing for Circulating Neoplastic Cells in Malignant Melanoma
Authors: Szenajch Jolanta , Jasiński Bogdan , Synowiec Agnieszka , Kulik Jadwiga , Chomicka Małgorzata , Strużyna Jerzy , Nowecki Zbigniew , Rutkowski Piotr , Ruka Włodzimierz , Kupść Witold , Siedlecki Janusz A , Wiktor-Jȩdrzejczak Wiesław 
Published: February 2004

Abstract
Background: The reverse transcription-PCR tyrosinase assay (TYR test) cannot reliably detect malignant melanoma (MM) cells in blood as the cells often circulate at low concentrations. We evaluated the prognostic value of multiple TYR testing, the prognostic significance of individual positive TYR test results (TYR+) in asymptomatic melanoma patients, and whether statistical analysis could help in the interpretation of results of a test that measures phenomena that typically occur below its detection threshold.
Methods: MM patients in stages I-IV (n = 150) underwent multiple testing with the TYR test during the course of their disease. TYR testing was performed as described by Smith et al. (Lancet 1991;38:1227–9). Statistical analyses were performed with the logistic function and t-test procedures.
Results: The relationship between MM stage and the frequency of TYR+ was statistically significant (P = 0.011). Higher frequency of TYR+ in clinically asymptomatic patients after complete resection of the primary tumor was associated with an increased risk of recurrence of MM (prognostic sensitivity, 62%; specificity, 78%).
Conclusions: A single positive TYR test provides a warning for disease relapse, suggesting that multiple TYR testing might provide more reliable predictions of disease progression. Multiple testing and statistical analysis using a logistic function might allow for the interpretation of apparently inconsistent results of tests for very rare cells.
Development and Assessment of a Quantitative Reverse Transcription-PCR Assay for Simultaneous Measurement of Four Amplicons
Authors: Grace Marcy B , McLeland Christopher B , Gagliardi Steven J , Smith Jeffrey M , Jackson William E , Blakely William F 
Published: February 2004

AbstractBackground: High-throughput and forward-deployable biological dosimetry capabilities are required for tactical and medical decisions after radiologic events. We previously reported a quantitative reverse transcription (QRT)-PCR assay for human radiation-responsive gene targets using a whole-blood ex vivo irradiation model, but we needed a multitarget assay on a smaller, less costly, real-time PCR detection system.Methods: We developed a quadruplex QRT-PCR assay in a 96-well, closed-plate format suitable for use with RNA extracted from whole blood. Four cDNA targets were simultaneously amplified in a sealed tube by hybridization to exonuclease probes, each conjugated to distinct fluorogenic reporters. A novel primer-limited 18S rRNA reference target was validated from serial dilutions of human total RNA. To test assay precision, we incorporated a positive-control cDNA mimic into duplex and quadruplex PCR reactions. The master mixture was supplemented with more enzyme, MgCl2, and deoxyribonucleotides. Simultaneous detection of four targets was evaluated in comparison with respective duplex QRT-PCR assays.Results: The simultaneous detection of three radiation-responsive genes by quadruplex QRT-PCR was quantitative, with gene expression changes similar to those observed with optimized duplex and triplex QRT-PCR assays. The 18S rRNA and GADD45 calibration curves (threshold cycle vs log10 cDNA) were linear and reproducible and showed optimal PCR efficiencies as indicated by slopes statistically equivalent to the theoretical value of −3.322.Conclusions: This is the first study of a quadruplex QRT-PCR assay. Our approach has diagnostic utility in the detection of biomarkers, biological and toxicologic agents, and genes of inherited diseases and cancer.
Unexpected Relationship between Plasma Homocysteine and Intrauterine Growth Restriction
Authors: Infante-Rivard Claire , Rivard Georges-Etienne , Gauthier Robert , Théorêt Yves 
Published: February 2004

Abstract
Background: Moderate hyperhomocysteinemia is considered a risk factor for thrombosis and atherosclerosis. We hypothesized that higher maternal and newborn homocysteine concentrations in plasma would increase the risk of intrauterine growth restriction through placental thrombosis.
Methods: We carried out a case-control study that included all cases born at our institution over a 2-year period whose birthweight was below the 10th percentiles for gestational age and sex according to Canadian norms; controls were born at the same period and institution at or above the 10th percentiles and were matched on gestational age, race, and sex. Homocysteine was measured in cord and maternal blood. The analysis included 483 case and 468 control mothers and 409 case and 438 control newborns.
Results: Homocysteine values were largely &lt;15 μmol/L. Contrary to expectation, within that range of values, increased plasma homocysteine, particularly in the mother, was protective against intrauterine growth restriction. With the case/control status as the outcome, the estimated odds ratio was 0.37 (95% confidence interval, 0.24–0.58) for a 5 μmol/L unit difference on the maternal homocysteine scale. With birthweight as the outcome, the estimated increase was 178.1 g (95% confidence interval, 92.5–263.7 g) for every 5 μmol/L unit increase in maternal homocysteine. Results were similar using newborn homocysteine concentrations.
Conclusions: The data suggest that, in contrast to the proposed hypothesis, mothers with small babies have lower homocysteine concentrations than those giving birth to larger ones.