bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Performance and Clinical Impact of a Rapid Intraoperative Parathyroid Hormone Assay in Conjunction with Preoperative Imaging and Concise Parathyroidectomy
Authors: Johnson Lawrence R , Doherty Gerard , Lairmore Terry , Moley Jeffrey F , Brunt L Michael , Koenig John , Scott Mitchell G 
Published: January 2020

Abstract
Background: 99mTc-sestamibi scans and rapid, intraoperative intact parathyroid hormone (PTH) assays allow preoperative identification of diseased glands and intraoperative confirmation of diseased gland removal, respectively. Use of these two new technologies may facilitate simpler, more concise surgery, shorter hospital stays, and decreased costs for frozen-section analysis. One major drawback to this new strategy has been the high cost of rapid point-of-care PTH assays.
Methods: We performed rapid PTH assays with the DPC Turbo PTH assay on the DPC IMMULITE automated analyzer. The number of intraoperative frozen sections, type of anesthesia, surgical approach, length of hospital stay, and pre- and postoperative calcium values were compared between a group of 49 patients undergoing parathyroidectomy where the intraoperative PTH assay was used in conjunction with preoperative imaging, and a historical control group of 55 patients before the use of these two technologies in our institution.
Results: Comparison of the Turbo PTH assay to the standard IMMULITE PTH assay gave the following: y = 1.08x − 4.36 (r = 0.97; n = 48). For the 49 patients, the median turnaround time for each intraoperative PTH determination was 19 min (range, 14–40 min). The median decrease in PTH values from baseline was 88% (range, 33–99%). Thirty-seven patients required two PTH determinations, 7 required three, 4 had four, and 1 required five determinations. The average laboratory cost for the rapid intraoperative PTH assays was &lt;$100 per patient (range, $55 to $113). Compared with the control group, the experimental group had significantly fewer frozen sections (1.4 vs 2.5; P &lt;0.0001), shorter hospital stays (17 discharged on the day of surgery vs none discharged on the day of surgery; P &lt;0.0001), greater use of local anesthesia (33% vs 0%; P &lt;0.001), and more unilateral, rather than bilateral neck explorations (65% vs 0%; P &lt;0.001).
Conclusions: The combination of intraoperative Turbo PTH assay and preoperative 99mTc-sestamibi scans can lead to significant decreases in laboratory and surgical pathology costs, hospital stays, and exposure to general anesthesia by facilitating concise parathyroidectomy surgery.
Fusion Proteins for Combined Analysis of Autoantibodies to the 65-kDa Isoform of Glutamic Acid Decarboxylase and Islet Antigen-2 in Insulin-dependent Diabetes Mellitus
Authors: Rickert Mathias , Seissler Jochen , Dangel Werner , Lorenz Helga , Richter Wiltrud 
Published: January 2020

AbstractBackground: Prediction, risk assessment, and diagnosis of autoimmune diseases often rely on detection of autoantibodies directed to multiple target antigens, such as the 65-kDa isoform of glutamic acid decarboxylase (GAD65-abs) and the tyrosine phosphatase-like protein islet antigen-2 (IA2-abs), the two major subspecificities of islet cell antibodies (ICAs) associated with insulin-dependent diabetes mellitus. We hypothesized that a combination of autoantigens in a fusion protein unifying the important immunodominant epitopes could provide an efficient target for cost-effective, one-step screening of sera.Methods: Chimeric proteins composed of GAD65 and IA2 residues were constructed, analyzed for their immune reactivity with monoclonal antibodies and sera, and used in a diagnostic assay with 35S-labeled protein as antigen.Results: Length and order of GAD65 and IA2 sequences were critical for conservation of the conformational epitopes in the fusion protein. Among four chimera tested, only IA2(606–979)/GAD65(1–585) retained wild-type-like folding of GAD65 and IA2 domains and yielded a stable protein after baculovirus expression. Reactivity of GAD65 antibody- and IA2 antibody-positive sera from patients newly diagnosed with insulin-dependent diabetes mellitus, from ICA-positive prediabetics, and from ICA-positive first-degree relatives demonstrated conservation of the relevant autoreactive epitopes. The assay based on the in vitro translated fusion antigen had a sensitivity and specificity identical to those for detection of GAD65- and IA2-abs based on the two separate GAD65 and IA2 proteins.Conclusions: Autoantigens such as GAD65 and IA2 can be combined successfully in a fusion protein of similar immune reactivity. This allows simultaneous detection of GAD65- and IA2-abs in a one-step screening assay and cost-effective identification of positive individuals at risk of diabetes or at onset of disease.
Management of Maternal Amanita phalloı̈des Poisoning during the First Trimester of Pregnancy: A Case Report and Review of the Literature
Authors: Boyer Jean-Christophe , Hernandez Francois , Estorc Jacques , De La Coussaye Jean-Emmanuel , Bali Jean-Pierre 
Published: January 2020

Abstract
Background: Amanita phalloı̈des poisoning produces acute liver failure and often death. Maternal poisonings are rare, and medical decisions of abortion or liver transplantation in this critical situation frequently are based on laboratory data. We report here the case of a 22-year-old-woman in the 11th week of pregnancy, who ingested mushrooms.
Case Report: The patient’s clinical symptoms (e.g., vomiting and diarrhea) and blood chemistry data (persistent increases of aspartate aminotransferase and alanine aminotransferase and severe decreases in prothrombin, factor V, factor II, factor VII, and factor X) indicated poisoning of medium severity. The management consisted of intravenous hydration, and administration of silymarine and N-acetylcysteine. No fetal damage was observed, and birth and development of the infant (now 2 years of age) proceeded without incident.
Conclusion: Abortion is not necessarily indicated in maternal poisoning by A. phalloı̈des, even in the first trimester of pregnancy.
Influence of Vitamin-optimized Plasma Homocysteine Cutoff Values on the Prevalence of Hyperhomocysteinemia in Healthy Adults
Authors: Fokkema M Rebecca , Weijer Jacomijn M , Dijck-Brouwer D A Janneke , van Doormaal Jasper J , Muskiet Frits A J 
Published: January 2020

Abstract
Background: Hyperhomocysteinemia is a cardiovascular disease (CVD) risk factor. We determined plasma homocysteine (Hcy) reference values at optimized vitamin status and investigated their influence on the prevalence of hyperhomocysteinemia in healthy adults. Results were compared with those obtained using European Concerted Action Project (ECAP) cutoff values.
Methods: Healthy adults (n = 101) received folic acid (5 mg/day) and vitamin B12 (1 mg/day) for 2 weeks and the same dosages of folic acid and vitamin B12 plus vitamin B6 (1 mg · kg−1 · day−1) during the following 2 weeks. Hcy concentrations, both fasting and 6-h post-methionine load, were determined at baseline and after 4 weeks.
Results: Baseline (4 weeks) fasting and 6-h postload Hcy reference values were 4.7–14.6 (4.1–9.3) and 18.8–49.7 (12.9–35.1) μmol/L, respectively. Mean fasting and 6-h postload Hcy decreased after 4 weeks of vitamin supplementation by 3.5 μmol/L (33.5%) and 8.5 μmol/L (26.3%), respectively. The percentages of subjects exhibiting significant decreases in fasting Hcy following vitamin supplementation were 88% (all subjects), 92% (non-vitamin users), and 72% (vitamin users). The prevalences of hyperhomocysteinemia with use of ECAP cutoff values were 29% for all groups, 29% for men, 27% for premenopausal women, and 53% for postmenopausal women. With vitamin-optimized cutoff values, prevalences were 58%, 58%, 76%, and 89%, respectively. Use of vitamin-optimized cutoff values increased the diagnostic value of fasting Hcy and decreased that of a 6-h postload Hcy compared with use of ECAP cutoff values.
Conclusions: Use of vitamin-optimized cutoff values gives rise to high hyperhomocysteinemia pretest probabilities in the general population and, therefore, precludes any meaningful role for Hcy testing. Future demonstration of a beneficial effect of decreasing Hcy on CVD risk would justify use of vitamin-optimized cutoff values for assessment of CVD risk.
Cardiac Troponin T and Creatine Kinase MB Are Not Increased in Exterior Oblique Muscle of Patients with Renal Failure
Authors: Fredericks Salim , Murray Joanne F , Bewick Michael , Chang René , Collinson Paul O , Carter Nicholas D , Holt David W 
Published: January 2020

AbstractBackground: Serum cardiac troponin T (cTnT) concentrations may be increased in patients with renal dysfunction without evidence of cardiac damage, as assessed by conventional methods. It has been suggested that these positive measurements result from the expression in skeletal muscle of fetal isoforms of cTnT, which are detected by the cTnT immunoassay.Methods: Skeletal muscle (exterior oblique) biopsies were taken from healthy living kidney donors (n = 5) and transplant recipients (n = 19). The amounts of cTnT and creatine kinase (CK) isoenzymes in skeletal muscle of healthy controls were compared with those in patients with renal failure (Wilcoxon–Mann–Whitney test). cTnT was measured quantitatively by a second-generation assay, with a limit of detection of 1 μg/g of protein, and qualitatively by immunohistochemistry and immunoblotting. CK-MB was measured by quantitative electrophoresis.Results: Minute quantities of cTnT were detected in 2 of the 5 (40%) control samples and 9 of the 19 (47%) renal failure samples, respectively, at mean concentrations of &lt;5 μg/g of protein for both subject groups. This was &lt;1/6000th that found in heart muscle. There was no significant difference in cTnT or CK-MB content in skeletal muscle between healthy controls and patients with renal failure. Increased serum cTnT did not predict detectable cTnT in skeletal muscle. cTnT was not detected qualitatively by immunoblotting or immunohistochemistry in any skeletal muscle samples.Conclusions: Uremia does not affect the content of cTnT or CK-MB in exterior oblique muscle, suggesting that cTnT detected in serum from patients with renal failure does not originate from skeletal muscle.
Electrospray Tandem Mass Spectrometry for Analysis of Acylcarnitines in Dried Postmortem Blood Specimens Collected at Autopsy from Infants with Unexplained Cause of Death
Authors: Chace Donald H , DiPerna James C , Mitchell Brenda L , Sgroi Bethany , Hofman Lindsay F , Naylor Edwin W 
Published: January 2020

Abstract
Background: Deaths from inherited metabolic disorders may remain undiagnosed after postmortem examination and may be classified as sudden infant death syndrome. Tandem mass spectrometry (MS/MS) may reveal disorders of fatty acid oxidation in deaths of previously unknown cause.
Methods: We obtained filter-paper blood from 7058 infants from United States and Canadian Medical Examiners. Acylcarnitine and amino acid profiles were obtained by MS/MS. Specialized interpretation was used to evaluate profiles for disorders of fatty acid, organic acid, and amino acid metabolism. The analyses of postmortem blood specimens were compared with the analyses of bile specimens, newborn blood specimens, and specimens obtained from older infants at risk for metabolic disorders.
Results: Results on 66 specimens suggested diagnoses of metabolic disorders. The most frequently detected disorders were medium-chain and very-long-chain acyl-CoA dehydrogenase deficiencies (23 and 9 cases, respectively), glutaric acidemia type I and II deficiencies (3 and 8 cases, respectively), carnitine palmitoyl transferase type II/translocase deficiencies (6 cases), severe carnitine deficiency (4 cases), isovaleric acidemia/2-methylbutyryl-CoA dehydrogenase deficiencies (4 cases), and long-chain hydroxyacyl-CoA dehydrogenase/trifunctional protein deficiencies (4 cases).
Conclusions: Postmortem metabolic screening can explain deaths in infants and children and provide estimates of the number of infant deaths attributable to inborn errors of metabolism. MS/MS is cost-effective for analysis of postmortem specimens and should be considered for routine use by Medical Examiners and pathologists in unexpected/unknown infant and child death.
Accumulation of Free 3-Hydroxy Fatty Acids in the Culture Media of Fibroblasts from Patients Deficient in Long-Chain l-3-Hydroxyacyl-CoA Dehydrogenase: A Useful Diagnostic Aid
Authors: Jones Patricia M , Moffitt Monica , Joseph Delanie , Harthcock Pamela A , Boriack Richard L , Ibdah Jamal A , Strauss Arnold W , Bennett Michael J 
Published: January 2020

AbstractBackground: The diagnosis of long-chain l-3-hydroxy-acyl-coenzyme A dehydrogenase (LCHAD) deficiency frequently requires the study of cultured fibroblasts. We developed such a test that does not require disruption and loss of the cells.Methods: We measured free 3-hydroxy fatty acids (3-OHFAs) in media of skin fibroblasts cultures from 11 patients with a genetic deficiency of LCHAD and the associated disorder of mitochondrial trifunctional protein (MTFP). Fibroblasts were cultured for 24 h with 100 μmol/L nonisotopic palmitate added. 3-OHFAs were measured by selected-ion monitoring, stable-isotope dilution gas chromatography-mass spectrometry with [13C]-labeled internal standards.Results: 3-OH-hexadecanoic and 3-OH-tetradecanoic FAs were increased 14- and 11-fold, respectively, in all patients with LCHAD or MTFP deficiency when compared with control fibroblast cell lines after overnight incubation with palmitate. 3-OH-dodecanoic FA demonstrated a modest, fivefold increase in LCHAD-deficient cells. The concentrations of all 3-OHFAs were similar whether or not the medium samples were hydrolyzed to release conjugated species such as acylcarnitines, suggesting that 3-OHFAs accumulate in the media as free FAs.Conclusions: Measurement of 3-OHFA excretion from LCHAD- or MTFP-deficient cell lines can be used as a diagnostic tool. Free FAs are the predominant form of these abnormal metabolic intermediates in culture media.
Interference of Transferrin Isoform Types with Carbohydrate-deficient Transferrin Quantification in the Identification of Alcohol Abuse
Authors: Helander Anders , Eriksson Gunne , Stibler Helena , Jeppsson Jan-Olof 
Published: January 2020

AbstractBackground: Isoforms of transferrin interfere with measurement of carbohydrate-deficient transferrin (CDT) as a marker of heavy alcohol consumption. We evaluated the rate of inaccurate CDT results by immunoassays.Methods: We studied 2360 consecutive sera (1614 individuals) submitted for CDT assay without clinical information as well as samples from 1 patient with a congenital disorder of glycosylation (CDG Ia) and from 6 healthy carriers of CDG Ia. The CDTect, %CDT-TIA, and new %CDT immunoassays were compared with HPLC (%CDT-HPLC). Transferrin isoform pattern were evaluated by isoelectric focusing (IEF).Results: Transferrin BC and CD heterozygotes were found at frequencies of ∼0.7% and ∼0.2%, respectively. Another transferrin C subtype, where di- and trisialotransferrin partly coeluted (tentatively identified as C2C3), was observed in ∼0.6%. Compared with the %CDT-HPLC method, the immunoassays often produced low results for transferrin BC and high results for transferrin CD and “C2C3”. A very high trisialotransferrin value (frequency ∼1%) often produced high CDT immunoassay results. In four of six healthy carriers of CDG Ia, a- and disialotransferrin were highly increased and the HPLC and IEF isoform patterns were indistinguishable from those in alcohol abuse.Conclusions: Rare transferrin isoform types and abnormal amounts of trisialotransferrin (total frequency ∼2–3%) may cause incorrect determination of CDT with immunoassays. The observed variants were readily identified by HPLC and IEF, which can be recommended for verification of CDT immunoassay results in doubtful cases. In healthy carriers of CDG Ia, CDT is high by all assays.
Direct and Indirect Free Thyroxine Assay Methods: Theory and Practice
Authors: Midgley John E M 
Published: January 2020

AbstractBackground: For the diagnosis of thyroid disease, measurement of “free hormone” is generally accepted as an appropriate measure. However, valid assays measuring the free fraction of thyroxine (FT4) ideally must perform without bias, despite large variations in the concentrations and affinities of serum T4-binding proteins in the population. Several approaches have been taken to overcome such bias, and these have created considerable controversy in the field over the past decade.Approach: This review, from both a historical and an analytical standpoint, charts the progress made over more than 30 years in improvements to the performance of assays in common use for the measurement of FT4 in serum or plasma. It reexamines the theory behind early approaches to such assays [for example, the free thyroxine index (FTI) method], that preceded more accurate, two-step immunoassays or one-step analog techniques. It evaluates the continuous refinements to the latter assays that by now have largely supplanted the FTI approach and where the deficiencies that so exercised clinical chemists in the past have been virtually eliminated in the leading assays.Content: The basic Mass Action theory underpinning all such methods is discussed by assessing how far each particular approach obeys the criteria the theory imposes. In this, it is not the intention of the review to dissect individual commercial or academic assays, but rather to give guidance where appropriate as to how any assay said to measure FT4 can be conveniently evaluated by those intending to use it. Examples are given where inappropriate tests may wrongly imply assay invalidity by misinterpreting how FT4 assays work.Summary: Detailed knowledge of the underlying theory is essential when devising tests for direct FT4 assays, to ensure that such tests do not overstep the practical limits of assay validity.
Genotyping Single-Nucleotide Polymorphisms by the Invader Assay with Dual-Color Fluorescence Polarization Detection
Authors: Hsu Tony M , Law Scott M , Duan Shenghui , Neri Bruce P , Kwok Pui-Yan 
Published: January 2020

AbstractBackground: The PCR-Invader® assay is a robust, homogeneous assay that has been shown to be highly sensitive and specific in genotyping single-nucleotide polymorphism (SNP) markers. In this study, we introduce two changes to improve the assay: (a) we streamline the PCR-Invader method by assaying both alleles for each SNP in one reaction; and (b) we reduce the cost of the method by adopting fluorescence polarization (FP) as the detection method.Methods: PCR product was incubated with Invader oligonucleotide and two primary probes at 93 °C for 5 min. Signal probes corresponding to the cleaved flaps of the primary probes [labeled with fluorescein and 6-carboxytetramethylrhodamine (TAMRA) dye] and Cleavase® VIII enzyme (a flap endonuclease) were then added to the mixture. This reaction mixture was incubated at 63 °C for 5 min. FP measurements were made with a fluorescence plate reader.Results: Eighty-eight individuals were genotyped across a panel of 10 SNPs, using PCR product as template, for a total of 880 genotypes. An average “no call” rate of 3.2% was observed after first round of experiments. PCR products were remade in those samples that failed to produce any genotype in the first round, and all gave clear-cut genotypes. When the genotypes determined by the PCR-Invader assay and template-directed dye-terminator incorporation assay with FP were compared, they were in 100% concordance for all SNP markers and experiments.Conclusions: The improvements introduced in this study make PCR-Invader assay simpler and more cost-effective, and therefore more suitable for high-throughput genotyping.
Integrated Patient Data for Optimal Patient Management: The Value of Laboratory Data in Quality Improvement
Authors: Emons Matthew F 
Published: January 2020

Abstract
Managed care organizations are shifting from traditional utilization management programs to focus on initiatives that improve the health of an insured population. This strategy requires sophisticated data integration to identify at-risk individuals and track outcomes. Laboratory data are becoming increasingly valuable tools for managed care organizations and healthcare providers. The HEDIS® Effectiveness of Care measures have incorporated laboratory data into several key performance indicators. By building a comprehensive repository of laboratory data that includes both procedure codes and laboratory values, managed care organizations can realize substantial savings by avoiding the costly medical record reviews required when administrative data are incomplete. In addition to tracking clinical outcomes, laboratory data provide the ability to risk-stratify a population to target high-risk individuals for case management and disease management interventions. Healthcare organizations face several challenges in the integration of laboratory data into medical databases and practice management software. Confidentiality is a key consideration in view of recent healthcare regulations. Providers of laboratory services should work collaboratively with organizations setting standards for healthcare informatics to facilitate the pooling of data for quality improvement and outcomes research. Health Level Seven, Inc. (HL7), Logical Observation Identifier Names and Codes (LOINC®), and Systematized Nomenclature of Medicine (SNOMED) will likely play a key role in this process.
Genotyping Energy-Transfer-Cassette-labeled Short-Tandem-Repeat Amplicons with Capillary Array Electrophoresis Microchannel Plates
Authors: Medintz Igor L , Berti Lorenzo , Emrich Charles A , Tom Jennifer , Scherer James R , Mathies Richard A 
Published: January 2020

Abstract
Background: Genetic analysis of microsatellite DNA is a powerful tool used in linkage analysis, gene mapping, and clinical diagnosis. To address the expanding needs of studies of short tandem repeats (STRs), we demonstrated high-performance STR analysis on a high-throughput microchannel plate-based platform.
Methods: Energy-transfer-cassette-labeled STR amplicons were separated and typed on a microfabricated 96-channel radial capillary array electrophoresis (CAE) microchannel plate system. Four-color detection was accomplished with a laser-excited confocal fluorescence rotary scanner.
Results: Multiplex STR analysis with single base-pair resolution was demonstrated on denaturing polyacrylamide gel media. The high-throughput multiplex capabilities of this genetic analysis platform were demonstrated by the simultaneous separation of STR amplicons representing 122 samples in ninety-six 5.5-cm-long channels in &lt;8 min. Sizing values obtained for these amplicons on the CAE microchannel plate were comparable to those measured on a conventional commercial CAE instrument and exhibit &lt;1% sizing variance.
Conclusions: Energy-transfer-cassette labeling and microfabricated CAE microchannel plates allow high-performance multiplex STR analyses.
Haptoglobin Polymorphism and Iron Homeostasis
Authors: Beutler Ernest , Gelbart Terri , Lee Pauline 
Published: January 2020

Abstract
Background: There is a marked difference in the degree of expression of the homozygous C282Y HFE genotype that is associated with hereditary hemochromatosis. It has been reported that individuals with the haptoglobin 2-2 type manifest increased iron concentrations, including serum iron, transferrin saturation, and ferritin.
Methods: We studied 232 patients, 115 homozygous for the c.845G→A (C282Y) mutation and 117 matched controls with the wild-type HFE genotype, for haptoglobin phenotypes. Haptoglobin types were determined by electrophoresis of the denatured protein. The HFE genotype was determined by allele-specific oligonucleotide hybridization. Ferritin and transferrin saturation were measured by standard methods.
Results:There was no relationship between haptoglobin type and ferritin concentration or transferrin saturation.
Conclusions: The effect of haptoglobin type on iron homeostasis cannot account for the marked phenotypic variation that is seen in patients homozygous for the HFE C282Y mutation.