bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Use of Infrared Spectrophotometry for Measuring Body Water Spaces
Authors: Jennings Graham , Bluck Leslie , Wright Antony , Elia Marinos 
Published: January 2020

AbstractBackground: The conventional method of measuring total body water by the deuterium isotope dilution method uses gas isotope ratio mass spectrometry (IRMS), which is both expensive and time-consuming. We investigated an alternative method, using Fourier transform infrared spectrophotometry (FTIR), which uses less expensive instrumentation and requires little sample preparation.Method: Total body water measurements in human subjects were made by obtaining plasma, saliva, and urine samples before and after oral dosing with 1.5 mol of deuterium oxide. The enrichments of the body fluids were determined from the FTIR spectra in the range 1800–2800 cm−1, using a novel algorithm for estimation of instrumental response, and by IRMS for comparison.Results: The CV (n = 5) for repeat determinations of deuterium oxide in biological fluids and calibrator solutions (400–1000 μmol/mol) was found to be in the range 0.1–0.9%. The use of the novel algorithm instead of the integration routines supplied with the instrument gave at least a threefold increase in precision, and there was no significant difference between the results obtained with FTIR and those obtained with IRMS.Conclusion: This improved infrared method for measuring deuterium enrichment in plasma and saliva requires no sample preparation, is rapid, and has potential value to the clinician.
The Lipoprotein Lipase HindIII Polymorphism: Association with Total Cholesterol and LDL-Cholesterol, but not with HDL and Triglycerides in 342 Females
Authors: Larson Ilona , Hoffmann Michael M , Ordovas Jose M , Schaefer Ernst J , März Winfried , Kreuzer Jörg 
Published: January 2020

AbstractBackground: Lipoprotein lipase (LPL) is the rate-limiting enzyme in the hydrolysis of core triglycerides in chylomicrons and VLDL.Methods: We investigated the association between the HindIII polymorphism of the LPL gene and fasting glucose, lipid, and lipoprotein concentrations in 683 Caucasians. We first stabilized the study subjects, using an 8-day diet and exercise intervention program before obtaining blood samples. The use of this standardization period reduced the variance of all glucose and lipid concentrations.Results: In our study, the HindIII allele frequencies for females and males were 0.29 and 0.34 for H− and 0.71 and 0.66 for H+, respectively. We found in females, but not in males, a significant association between the HindIII genotype and total cholesterol (P = 0.007) and LDL-cholesterol (P = 0.018), with females homozygous for the rare H− allele having the lowest, heterozygotes (H−/+) having intermediate, and women homozygous for the common H+ allele having the highest of each of these lipid traits. With regard to triglycerides, HDL-cholesterol, and glucose, no significant effect of the HindIII genotype was noted in either gender.Conclusions: These results suggest that in a gender-specific manner, the rare LPLHindIII H− allele has a cholesterol-lowering and, therefore, potentially cardioprotective effect compared with the common H+ allele.
Estimation of Prostate Cancer Probability by Logistic Regression: Free and Total Prostate-specific Antigen, Digital Rectal Examination, and Heredity Are Significant Variables
Authors: Virtanen Arja , Gomari Mehran , Kranse Ries , Stenman Ulf-Håkan 
Published: January 2020

Abstract
Background: Despite low specificity, serum prostate-specific antigen (PSA) is widely used in screening for prostate cancer. Specificity can be improved by measuring free and total PSA and by combining these results with clinical findings. Methods such as neural networks and logistic regression are alternatives to multistep algorithms for clinical use of the combined findings.
Methods: We compared multilayer perceptron (MLP) and logistic regression (LR) analysis for predicting prostate cancer in a screening population of 974 men, ages 55–66 years. The study sample comprised men with PSA values &gt;3 μg/L. Explanatory variables considered were age, free and total PSA and their ratio, digital rectal examination (DRE), transrectal ultrasonography, and a family history of prostate cancer.
Results: When at least 90% sensitivity in the training sets was required, the mean sensitivity and specificity obtained were 87% and 41% with LR and 85% and 26% with MLP, respectively. The cancer specificity of an LR model comprising the proportion of free to total PSA, DRE, and heredity as explanatory variables was significantly better than that of total PSA and the proportion of free to total PSA (P &lt;0.01, McNemar test). The proportion of free to total PSA, DRE, and heredity were used to prepare cancer probability curves.
Conclusion: The probability calculated by logistic regression provides better diagnostic accuracy for prostate cancer than the presently used multistep algorithms for estimation of the need to perform biopsy.
Possible Mechanism for in Vitro Complement Activation in Blood and Plasma Samples: Futhan/EDTA Controls in Vitro Complement Activation
Authors: Pfeifer Philippe H , Kawahara Marleen S , Hugli Tony E 
Published: January 2020

AbstractBackground: Ongoing in vitro complement (C) activation in citrate or EDTA plasma has prevented an accurate analysis of C-activation products generated in vivo. The aim of this study was to characterize handling and storage conditions required to prevent in vitro C activation in blood and plasma samples collected with Futhan/EDTA.Methods: BiotrakTM RIAs were used to quantitatively measure C3a and C4a in blood and/or plasma samples from healthy individuals (controls) and from liver transplant patients. Blood samples were routinely drawn into either EDTA (1 g/L) tubes or into tubes containing both EDTA (1 g/L) and Futhan (0.1 g/L) and immediately centrifuged at 2000g for 15 min at 4 °C.Results: In controls, C4a, but not C3a, in fresh samples (time 0) was higher in EDTA plasma than in Futhan/EDTA plasma (n = 20; P = 0.002). Futhan/EDTA prevented C3a and C4a generation in blood and plasma samples held at room temperature (22–23 °C) for 1 h and in plasma held for 24 h at 4 °C or −70 °C. The mean C3a concentration (1.76 mg/L; n = 19) at time 0 in EDTA plasma samples from liver transplant patients was significantly higher than for controls (0.34 mg/L; n = 11). In these patients, the mean C3a in EDTA samples increased to 13.8 mg/L after 60 min at room temperature, but there was no change in the C3a concentration of an EDTA plasma from a control. In the patients, C3a concentrations were lower in Futhan/EDTA plasma than in EDTA at time 0 and after 60 min at room temperature (1.40 and 2.02 mg/L, respectively). The mean patient C4a was 4.02 mg/L in EDTA plasma at time 0 vs 0.24 mg/L for controls; it increased to 16.9 mg/L after 60 min at room temperature compared with 0.76 mg/L for controls. The mean patient C4a was 0.83 mg/L in Futhan/EDTA plasma at time 0 vs 0.1 mg/L for controls. Neither patient nor control C4a concentrations increased vs time in Futhan/EDTA.Conclusion: The combination of Futhan (0.1 g/L) and EDTA (1 g/L) eliminates in vitro C activation.
Type 2 Diabetes: An Overview
Authors: Lebovitz Harold E 
Published: January 2020

Abstract
Type 2 diabetes is a heterogeneous disorder. Clinical expression of the disorder requires both genetic and environmental factors. One theory concerning its etiology is that it is the result of the evolution of a thrifty genotype that had survival benefits in the past but is detrimental in the current environment. An opposing theory is that it represents an adult metabolic response to fetal malnutrition. Hyperglycemia in type 2 diabetes results from absolute or relative insulin deficiency. Most often relative insulin deficiency is attributable to an inability to adequately compensate for insulin resistance. Insulin resistance may be caused by a variety of genetic or metabolic factors. The most common etiological factor in insulin resistance is central obesity. Insulin resistance is associated with a cluster of metabolic abnormalities that include glucose intolerance, hypertension, a unique dyslipidemia, a procoagulant state, and an increase in macrovascular disease. Clinical intervention studies have demonstrated that reduction in the chronic microvascular and macrovascular complications of type 2 diabetes requires treatment of hyperglycemia to achieve hemoglobin A1c &lt;7.0%, blood pressure ≤130/80 mmHg, and plasma LDL-cholesterol ≤2.6 mmol/L (≤100 mg/dL). Oral antihyperglycemic agents increase endogenous insulin secretion, decrease insulin resistance, or lower postprandial plasma glucose rise by delaying absorption of complex carbohydrates. Long-term glycemic control in type 2 diabetes requires progressive, stepwise, combination treatment with oral agents and eventually combination treatment with oral agents and insulin.
Hormonal Control of Calcium Homeostasis
Authors: Mundy Gregory R , Guise Theresa A 
Published: January 2020

Abstract
Calcium homeostasis in the extracellular fluid is tightly controlled and defended physiologically. Hypercalcemia always represents considerable underlying pathology and occurs when the hormonal control of calcium homeostasis is overwhelmed. The major hormones that are responsible for normal calcium homeostasis are parathyroid hormone and 1,25-dihydroxyvitamin D; these hormones control extracellular fluid calcium on a chronic basis. Over- or underproduction of these hormones or the tumor peptide, parathyroid hormone-related peptide, are the major causes of aberrant extracellular fluid calcium concentrations. These hormonal defense mechanisms are reviewed here.
The Endocrinology of Aging
Authors: Perry Horace M 
Published: January 2020

AbstractPhysiologic systems have substantial reserves in younger individuals. The process of aging and intercurrent pathologic processes gradually eliminate these reserves. Changes in endocrine systems, including menopause in women, androgen deficiency in men, loss of skeletal mass, decrease in growth hormone serum concentrations, and increased incidence of type 2 diabetes are all more common or certain in older individuals. This review summarizes the progression of each of these processes with age, the potential outcomes of the untreated process, and the treatment outcomes for these age-related losses. Maintenance of a premenopausal lipid profile presumably protects against cardiovascular events. Maintenance of skeletal mass reduces fracture risk and risk for loss of mobility and independence. Testosterone replacement in hypogonadal older men improves strength and presumably function and independence. Growth hormone therapy is reported to have similar effects. Improvement of long-term outcomes in older type 2 diabetics, however, is more difficult to demonstrate.
Drug Monitoring of Antiretroviral Therapy for HIV-1 Infection: Method Validation and Results of a Pilot Study
Authors: Moyer Thomas P , Temesgen Zelalem , Enger Robert , Estes Lynn , Charlson Joel , Oliver Lawrence , Wright Alan 
Published: January 2020

Abstract
Background: Antiretroviral therapy for HIV-1 infection has become increasingly complex. The availability of new and potent drugs and progress in understanding the pathogenesis of HIV-1 infection have led to the establishment of new treatment paradigms. The varying dosing regimens, associated toxicities, and the potential for drug-drug and food-drug interactions further complicate treatment. This complexity contributes to patient nonadherence. Because clinicians have no tools to monitor adherence or drug-drug interactions and because response requires that therapy exceed the known inhibiting concentration, serum monitoring of antiretroviral therapy may play a role in improving treatment of HIV-1 infection. We report methods to quantify serum concentrations of antiretroviral drugs used to treat HIV-1 infection, precision and interference studies of these methods, and results observed in a pilot evaluation of blood serum concentrations from 12 human subjects.
Methods: HPLC offers adequate sensitivity to measure peak or trough serum concentrations of delavirdine, lamivudine, nevirapine, indinavir, nelfinavir, ritonavir, and saquinavir and peak serum concentrations of stavudine, zidovudine, and didanosine with reasonable precision.
Results: Peak indinavir serum concentrations in most patients were in the range of 1–10 mg/L, and trough concentrations were in the range of 0.1–0.5 mg/L. Peak stavudine concentrations were in the range of 0.3–1.3 mg/L, and trough concentrations were in the range of 0.1–0.5 mg/L. Peak zidovudine concentrations were in the range of 0.1–1.1 mg/L.
Conclusions: Because this was a blood serum concentration-seeking pilot study to evaluate analytic performance, we do not report on the correlation of drug response to blood concentration. However, the concentrations observed in patients are generally consistent with blood concentrations reported from studies of monotherapy.
Inhibition of Stimulated Interleukin-2 Production in Whole Blood: A Practical Measure of Cyclosporine Effect
Authors: Stein C Michael , Murray John J , Wood Alastair JJ 
Published: January 2020

Abstract
Background: Prediction of cyclosporine (CSA) efficacy and toxicity in individual patients is difficult. There is no practical, biologically relevant, pharmacodynamic measure of CSA effect. A major effect of CSA is to decrease interleukin-2 (IL-2) production; however, measurement of this effect in isolated lymphocytes as a marker of response to CSA has been problematic.
Methods: CSA inhibition of phytohemagglutinin-P (PHA)-stimulated IL-2 production, measured by ELISA, was studied ex vivo in whole blood drawn before, and after subjects received 4 mg/kg oral CSA.
Results: Four hours after CSA was administered, the mean (± SD) CSA concentration was 702 ± 196 μg/L and PHA-stimulated IL-2 production decreased by 68.7% ± 17.2% (P &lt;0.0001; n = 17). Twenty-four hours after CSA was administered, concentrations were low (64 ± 24 μg/L), with no inhibition of IL-2 production. A rapid, concentration-dependent response occurred. Maximum CSA concentrations (944 ± 187 μg/L) and maximum inhibition of IL-2 production (86.9% ± 13.7%) occurred 90 min after subjects received CSA. In vitro, 32.5–1200 μg/L CSA also inhibited PHA-stimulated IL-2 production in whole blood in a dose-dependent fashion with a similar IC50 (∼300–400 μg/L) ex vivo and in vitro.
Conclusion: In the search for a pharmacodynamic marker to better guide immunosuppressive therapy, the relationship between this simple, biologically relevant measure of CSA effect and clinical outcome should be determined.
Predictive Value of Cord Blood Hematological Indices and Hemoglobin Barts for the Detection of Heterozygous α-Thalassemia-2 in an African-Caribbean Population
Authors: van der Dijs Fey PL , Volmer Marcel , van Gijssel-Wiersma Dieuwke G , Smit Jan W , van Veen Reind , Muskiet Frits AJ 
Published: January 2020

Abstract
Background: Cord blood hemoglobin Barts (HbBarts) and hemocytometric indices may be used for classification of newborns into those without α-thalassemia-2 (αα/αα) and with heterozygous α-thalassemia-2 (-α3.7/αα). We investigated by logistic regression analysis whether the combination of HbBarts and hemocytometric indices improves classification compared with classification based on a single analyte.
Methods: HbBarts percentages and hemocytometric indices were determined in cord blood of 208 consecutive newborns in Curaçao (Netherlands Antilles). Of these, 157 had αα/αα and 51 had -α3.7/αα, as established by DNA analysis.
Results: Between-group differences were significant for erythrocytes, mean cell volume, mean cell hemoglobin (MCH), mean cell hemoglobin concentration, platelets, hemoglobin F0 (HbF0), and HbBarts. The Logit equation of the logistic regression model, using MCH (pg) and HbBarts (%), was: 42.7164 + 5.7916(HbBarts) − 1.3110(MCH). A sensitivity of 100% was reached at a Logit value of −3.70. The corresponding specificity was 62.2%, and the predictive value of a positive test (PV+) was 46.3% (95% confidence interval, 37.0–55.7%). The relative information gains were as follows: 88% for the HbBarts-MCH combination, 26% for MCH (not significant), and 0% for HbBarts compared with the 24.6% -α3.7/αα prevalence.
Conclusion: Combined use of cord blood HbBarts and MCH improves classification compared with classification based on single hemocytometric indices.
Development, Characterization, and Use of Monoclonal Antibodies Made to Antigens Expressed on the Surface of Fetal Nucleated Red Blood Cells
Authors: Alvarez Francisco V , Olander Jitka , Crimmins Dan , Prieto Belén , Paz Ana , Alonso Rebeca , Porter Sharon , Hess Jay , Crist Robert D , Landt Yvonne , Ladenson Jack H 
Published: January 2020

Abstract
Background: Current methods for obtaining fetal cells for prenatal diagnosis are invasive and carry a small (0.5–1.0%) but definite risk of miscarriage. An attractive alternative would be isolation of fetal cells from peripheral maternal blood using antibodies with high specificity and avidity.
Methods: To generate antibodies, we purified nucleated red blood cells (NRBCs) from fetal livers and used them as the immunogen to generate monoclonal antibodies (mAbs) directed against surface antigens.
Results: The four antibodies recognized at least two conformationally sensitive epitopes of the transferrin receptor. Isolation of NRBCs from 252 maternal blood samples using these antibodies in magnetic activated cell sorting after an initial density gradient centrifugation yielded 0–419 NRBCs per 25 mL of maternal blood. One antibody, 2B7.4, not only isolated the highest number of NRBCs (&gt;10 in 90% of the samples) but also isolated these NRBCs in 78 consecutive maternal samples.
Conclusion: Antibody 2B7.4 shows promise for the isolation of NRBCs from maternal blood and should allow studies concerning the source of these cells, fetal vs maternal, and the factors controlling their prevalence.
Aptamers: An Emerging Class of Molecules That Rival Antibodies in Diagnostics
Authors: Jayasena Sumedha D 
Published: January 2020

AbstractAntibodies, the most popular class of molecules providing molecular recognition needs for a wide range of applications, have been around for more than three decades. As a result, antibodies have made substantial contributions toward the advancement of diagnostic assays and have become indispensable in most diagnostic tests that are used routinely in clinics today. The development of the systematic evolution of ligands by exponential enrichment (SELEX) process, however, made possible the isolation of oligonucleotide sequences with the capacity to recognize virtually any class of target molecules with high affinity and specificity. These oligonucleotide sequences, referred to as “aptamers”, are beginning to emerge as a class of molecules that rival antibodies in both therapeutic and diagnostic applications. Aptamers are different from antibodies, yet they mimic properties of antibodies in a variety of diagnostic formats. The demand for diagnostic assays to assist in the management of existing and emerging diseases is increasing, and aptamers could potentially fulfill molecular recognition needs in those assays. Compared with the bellwether antibody technology, aptamer research is still in its infancy, but it is progressing at a fast pace. The potential of aptamers may be realized in the near future in the form of aptamer-based diagnostic products in the market. In such products, aptamers may play a key role either in conjunction with, or in place of, antibodies. It is also likely that existing diagnostic formats may change according to the need to better harness the unique properties of aptamers.
Analytical Characterization of Electrochemical Biosensor Test Strips for Measurement of Glucose in Low-Volume Interstitial Fluid Samples
Authors: Collison Michael E , Stout Philip J , Glushko Tatyana S , Pokela Kristen N , Mullins-Hirte Debra J , Racchini Joel R , Walter Melissa A , Mecca Steve P , Rundquist Joanna , Allen John J , Hilgers Michael E , Hoegh Thomas B 
Published: January 2020

AbstractBackground: Minimally invasive interstitial fluid (ISF) sampling and glucose measurement technologies were integrated into a hand-held device for diabetic glucose monitoring investigations.Methods: Conventional electrochemical test strip technology (Bayer Glucometer Elite®) was adapted to measure glucose in small (0.5–2.0 μL) samples of ISF. Test strip glucose measurements were performed on a commercial potentiostat and were compared to various reference glucose methodologies (YSI 2300 analyzer, microhexokinase procedure, Bayer Glucometer Elite). Characterizations of the integrated ISF sampling-glucose test strip design included accuracy and precision in various sample media (saline, ISF surrogates, diabetic ISF samples), sample volume dependence, test strip sterilization studies (electron beam, γ irradiation), and diabetic ISF sampling and glucose measurements.Results: Glucose measurements were free from significant media effects. Sample volume variations (0.6–3.2 μL) revealed only modest dependence of glucose measurement bias on sample volume (−1.5% per microliter). Sterilization treatments had only a minor impact on glucose response and test strip aging and no significant impact on interferent responses of the glucose test strips. Diabetic subject testing under minimum fasting conditions of at least 2 h with integrated ISF sampling and glucose measurement gave low ISF glucose measurement imprecision (CV, 4%) and mean glucose results that were indistinguishable from reference (microhexokinase) ISF glucose measurements and from capillary blood glucose measurements (Glucometer Elite).Conclusions: Conventional single-use, electrochemical glucose test strip and ISF collection technologies can be readily integrated to provide real-time ISF sampling and glucose measurements for diabetic monitoring applications.
Genetic Analysis of the CYP2D6 Locus in a Hong Kong Chinese Population
Authors: Garcia-Barceló Mercè , Chow Lok Yee , Chiu Helen Fung Kum , Wing Yun Kowk , Lee Dominic Tak Shing , Lam Kwok Lim , Waye Mary Miu Yee 
Published: January 2020

Abstract
Background: The cytochrome P450 CYP2D6 enzyme debrisoquine 4-hydroxylase metabolizes many different classes of commonly used drugs, such as tricyclic antidepressants and neuroleptics. Genetic polymorphism of the CYP2D6 gene is responsible for pronounced interindividual and interracial differences in the metabolism of these drugs. The CYP2D6*10 allele and its variants are the most frequent alleles found in Orientals, and they are responsible for diminished debrisoquine 4-hydroxylase activity because of the presence of a C188→T mutation in exon 1.
Methods: One hundred nineteen Hong Kong Chinese subjects were genotyped by means of allele-specific PCR, PCR, and restriction enzyme analysis for 10 CYP2D6 alleles (CYP2D6*1, *2, *4D, *5, *8/*14, *10A, *10B, *15, *16, and J9).
Results: CYP2D6*10B was the most prevalent allele, and CYP2D6*10/CYP2D6*10 was the most frequent genotype, representing 46.22% of the population.
Conclusions: There was no significant difference in the prevalence of the alleles analyzed between our study and the Chinese populations genotyped previously. This is the largest study in terms of the number of CYP2D6 alleles analyzed in an Oriental population and the first one conducted in a Hong Kong Chinese population.