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Determination of aluminum by chemical and instrumental neutron activation analysis in biological standard reference material and human brain tissue.

Since aluminum is an extremely difficult element to determine reliably in biological samples, no National Institute of Standards and Technology (NIST) biological standard reference material for tissue has yet been certified for aluminum. A chemical neutron activation analysis procedure employing anion-exchange chromatography was developed. The procedure proved successful in decontaminating radioactivatable sodium and chlorine and phosphorus which can produce aluminum via a fast neutron bombardment. For bovine liver (NIST SRM 1577 a) a value of 2.1 +/- 0.2 micrograms of aluminum/g of sample was determined, comparing favorably to the uncertified value 2 micrograms/g sample. For freeze-dried urine (NIST SRM 2670) a value of 0.18 +/- 0.01 micrograms of aluminum/mL of urine was observed. Its uncertified value is 0.18 micrograms of aluminum/mL of sample. Twenty three individual samples in three different human brains were analyzed for their aluminum content.

Aluminum↗

[Chlormadinone Acetate Reference Standard (Control 881) of National Institute of Hygienic Sciences].

Chlormadinone acetate was tested for the preparation of the "Chlormadinone Acetate Reference Standard (Control 881)". Analytical data obtained were as follows: loss on drying, 0.00%; infrared spectrum, 1740, 1715, 1658, 1604, 1587, 1256, 1244 cm-1; ultraviolet spectrum, lambda max = 284 nm; absorbance, E1cm1% (284 nm) = 539-549; optical rotation, [alpha]D20: -12.1 degrees; melting point, 214.6 degrees C; thin-layer chromatography, contaminants were not detected until 300 micrograms; high-performance liquid chromatography, one contaminant was detected. On the basis of the above results, this material was authorized as the National Institute of Hygienic Sciences Reference Standard (Control 881).

Chlormadinone Acetate↗

[Epitiostanol Reference Standard (Control 891) of National Institute of Hygienic Sciences].

The raw material of epitiostanol was examined for preparation of "Epitiostanol Reference Standard". Analytical results for the sample were as follows: melting point 130.7 degrees C (decomposition); UV spectrum indicates absorption maximum at 263 nm in ethanol; IR spectrum indicates specific absorption at 2920, 1383, 1056 and 590 cm-1; optical rotation [alpha]20D+ 24.4 degrees; no impurity was found by TLC, but a small amount of one was found by HPLC analysis and the purity is assumed to be 99.5%; water content 1.52%. Based on the results, the present raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.

Androstanols↗

Reference standards, judges, and comparison subjects: roles for experts in evaluating system performance.

Medical informatics systems are often designed to perform at the level of human experts. Evaluation of the performance of these systems is often constrained by lack of reference standards, either because the appropriate response is not known or because no simple appropriate response exists. Even when performance can be assessed, it is not always clear whether the performance is sufficient or reasonable. These challenges can be addressed if an evaluator enlists the help of clinical domain experts. 1) The experts can carry out the same tasks as the system, and then their responses can be combined to generate a reference standard. 2)The experts can judge the appropriateness of system output directly. 3) The experts can serve as comparison subjects with which the system can be compared. These are separate roles that have different implications for study design, metrics, and issues of reliability and validity. Diagrams help delineate the roles of experts in complex study designs.

Evaluation Studies as Topic↗

Alternative referent standards for cardiac normality. Implications for diagnostic testing.

The radionuclide ventriculographic exercise response was evaluated in three patient populations representing alternative referent standards for cardiac normality: patients with normal coronary arteriograms, healthy volunteers, and uncatheterized patients with a low probability of coronary artery disease. Disease probability was determined by Bayesian analysis of age, sex, symptoms, and the results of cardiac fluoroscopy, exercise electrocardiography, or thallium scintigraphy. A wide range of ventriculographic responses was noted in the 62 catheterized normal patients; 21 (34%) had an abnormal ejection fraction response and 22 (35%) had an abnormal wall motion response. In contrast, the ejection fraction and wall motion responses were normal in the 9 volunteers. In 90 patients (18 catheterized and 72 uncatheterized) who had low disease probability (less than 1%), abnormal responses were rare; the ejection fraction response was abnormal in only 7% and the wall motion response was abnormal in 8%. Thus, these three populations are not equivalent referent standards of normality. Volunteers and patients with low disease probability provide too strict a standard, and their use can overestimate test specificity; catheterized normal patients, on the other hand, provide too lenient a standard, and their use can underestimate test specificity.

Adult↗

[Cyclandelate Reference Standard (Control 901) of National Institute of Hygienic Sciences].

The raw material of cyclandelate was examined for preparation of the "Cyclandelate Reference Standard". Analytical data obtained were as follows: melting point, 60 degrees C; ultraviolet spectrum, lambda max = 252, 258 and 264 nm E1%1cm = 6.1 (252 nm), 7.5 (258 nm), 5.9 (264 nm); infrared spectrum, 3454, 2948, 1730, 1453, 1202, 737, 695 cm-1; thin-layer chromatography, no impurities were detected until 1000 micrograms; high-performance liquid chromatography (HPLC), one impurity was detected, loss on drying, 0.00%. Based on the above results, this raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.

Chromatography, High Pressure Liquid↗

Assignment of additional anticapsular antibody concentrations to the Neisseria meningitidis group A, C, Y, and W-135 meningococcal standard reference serum CDC1992.

We assigned additional enzyme-linked immunosorbent assay antibody concentrations (immunoglobulin G [IgG], IgM, and IgA, and total) to the Neisseria meningitidis standard reference serum CDC1992 for groups Y and W-135 to 12 Centers for Disease Control and Prevention quality control sera. These assignments will supplement previous assignments and will aid in the evaluation of present and developing vaccines.

Antibodies, Bacterial↗

[Mestranol Reference Standard (Control 881) of National Institute of Hygienic Sciences].

The raw material of mestranol was examined for preparation of the "Mestranol Reference Standard". Analytical results for the sample were as follows: UV spectrum indicated absorption maxima at 279 and 287 nm and absorptivity at 279 nm E1%1cm 66; IR spectrum indicated specific absorption at 1612, 1578, 1505, 1253, and 1060 cm-1; optical rotation +3.9 degrees; melting point 153.1 degrees; loss on drying 0.03%; TLC and HPLC analyses indicated one impurity, respectively; the purity was assumed to be 99.3% by HPLC analysis. Based on the results, the present raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.

Chromatography, High Pressure Liquid↗

Perfusion magnetic resonance imaging predicts patient outcome as an adjunct to histopathology: a second reference standard in the surgical and nonsurgical treatment of low-grade gliomas.

OBJECTIVE: To determine whether relative cerebral blood volume (rCBV) can predict patient outcome, specifically tumor progression, in low-grade gliomas (LGGs) and thus provide a second reference standard in the surgical and postsurgical management of LGGs. METHODS: Thirty-five patients with histologically diagnosed LGGs (21 low-grade astrocytomas and 14 low-grade oligodendrogliomas and low-grade mixed oligoastrocytomas) were studied with dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging. Wilcoxon tests were used to compare patients in different response categories (complete response, stable, progressive, death) with respect to baseline rCBV. Log-rank tests were used to evaluate the association of rCBV with survival and time to progression. Kaplan-Meier time-to-progression curves were generated. Tumor volumes and CBV measurements were obtained at the initial examination and again at follow-up to determine the association of rCBV with tumor volume progression. RESULTS: Wilcoxon tests showed patients manifesting an adverse event (either death or progression) had significantly higher rCBV (P = 0.003) than did patients without adverse events (complete response or stable disease). Log-rank tests showed that rCBV exhibited a significant negative association with disease-free survival (P = 0.0015), such that low rCBV values were associated with longer time to progression. Kaplan-Meier curves demonstrated that lesions with rCBV less than 1.75 (n = 16) had a median time to progression of 4620 +/- 433 days, and lesions with rCBV more than 1.75 (n = 19) had a median time to progression of 245 +/- 62 days (P < 0.005). Lesions with low baseline rCBV (< 1.75) demonstrated stable tumor volumes when followed up over time, and lesions with high baseline rCBV (> 1.75) demonstrated progressively increasing tumor volumes over time. CONCLUSION: Dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging may be used to identify LGGs that are either high-grade gliomas, misdiagnosed because of sampling error at pathological examination or that have undergone angiogenesis in the progression toward malignant transformation. This suggests that rCBV measurements may be used as a second reference standard to determine the surgical management/risk-benefit equation and postsurgical adjuvant therapy for LGGs.

Adolescent↗

[Pyridoxine hydrochloride reference standard (Control 911) of the National Institute of Hygienic Sciences].

The raw material of pyridoxine hydrochloride was examined for preparation of the "Pyridoxine Hydrochloride Reference Standard". Analytical data obtained were as follows: loss on drying, 0.00%; pH, 2.87; melting point, 204.6 degrees C (decomposition); infrared spectrum, same as Pyridoxine Hydrochloride Reference Standard (Control 879); thin-layer chromatography, nonimpurities were detected; assay, 100.0% by non-aqueous titration and 100.0% by UV spectrophotometry. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Standard (Control 911).

Chromatography, Thin Layer↗

[Ulinastatin reference standard (Control 941) of the National Insutitute of Health Sciences].

The raw material of ulinastatin was examined for preparation of the "Ulinastatin Reference standard". The candidate material was evaluated in collaboration with one domestic laboratory, and the potency of trypsin inhibiting activity was determined to be 3500 unit/vial. Other analytical data obtained were as follows: UV maximum absorption was observed at 276 nm, the molecular weight was estimated to be about 66000 +/- 5000 by gel filtration method. Maximum variance of material contents in 10 vials was 6.52% by means of the weight variation test in JP XII. Based on the above results, this raw material was authorized to be the first "Ulinastatin Reference Standard" of the National Institute of Health Sciences.

Glycoproteins↗

Human anti-DNA antibody: reference standards for diagnosis and management of systemic lupus erythematosus.

A technique for the measurement of DNA binding activity of sera is described which uses primary internal reference standards in a Farr assay. This allows the DNA binding activity of test sera to be measured in relation to the reference standards and the results are expressed as units/ml. The use of this standardized assay has led to diminished interassay variation and close interlaboratory correlation, and has provided a clinically useful test. In survey using the standardized assay, normal sera were found to have binding activity which did not exceed 15 units/ml; 71% of patients with systemic lupus erythematosus (SLE) had levels greater than 25 units/ml; while only 8% of patients with diseases other than SLE had levels above 25 units/ml. Values between 15 and 25 units/ml appeared to have little diagnostic significance.

Antibodies↗

Standard Reference Materials for dioxins and other environmental pollutants.

The National Institute of Standards and Technology issues approximately 1100 Standard Reference Materials (SRMs) certified for chemical composition or physical properties. A number of these SRMs has been developed to assist chemists in analyzing environmental samples more reliably for chlorinated dioxins and other organic pollutants. Certification of the pollutant concentration in a natural matrix SRM is based on concordant analyses by the NIST Organic Analytical Research Division using at least two independent methods. For a calibration solution, such as SRM 1614, Dioxin (2,3,7,8-TCDD) in Isooctane, certification is based on agreement of the calculated concentration based on the gravimetric preparation and the concentration as determined experimentally. SRM 1614 also includes a 13C-labeled 2,3,7,8-TCDD for use as an internal standard in methods based on gas chromatography/mass spectrometry. The certified concentrations (ng g-1) are 98.3 +/- 3.3 for the unlabeled dioxin and 95.6 +/- 1.5 for the labeled dioxin. The certificates for SRM 1588, Organics in Cod Liver Oil, and SRM 1589, Polychlorinated Biphenyls (as Aroclor 1260) in Human Serum, provide noncertified concentrations of dioxins. Concentrations of chlorinated dioxins in two urban particulate SRMs have been reported in the literature.

Dioxins↗

Two new marine sediment standard reference materials (SRMs) for the determination of organic contaminants.

Two new marine sediment standard reference materials (SRMs), SRM 1941b Organics in Marine Sediment and SRM 1944 New York/New Jersey Waterway Sediment, have been recently issued by the National Institute of Standards and Technology (NIST) for the determination of organic contaminants including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyl (PCB) congeners, and chlorinated pesticides. Both sediment SRMs were analyzed using multiple analytical methods including gas chromatography/mass spectrometry (GC/MS) on columns with different selectivity, reversed-phase liquid chromatography with fluorescence detection (for PAHs only), and GC with electron capture detection (for PCBs and pesticides only). SRM 1941b has certified concentrations for 24 PAHs, 29 PCB congeners, and 7 pesticides, and SRM 1944 has certified concentrations for 24 PAHs, 29 PCB congeners, and 4 pesticides. Reference concentrations are also provided for an additional 58 (SRM 1941b) and 39 (SRM 1944) PAHs, PCB congeners, and pesticides. SRM 1944, which was collected from multiple sites within New York/New Jersey coastal waterways, has contaminant concentrations that are generally a factor of 10-20 greater than SRM 1941b, which was collected in the Baltimore (Maryland) harbor. These two SRMs represent the most extensively characterized marine sediment certified reference materials available for the determination of organic contaminants.

Environmental Monitoring↗

Comparative studies of the toxicity of standard reference materials in various cytotoxicity tests and in vivo implantation tests.

Polyurethane films that contained various amounts of zinc diethyldithiocarbamate (ZDEC) and zinc dibutyldithiocarbamate (ZDBC) were prepared as standard reference materials (SRM). Using three cell lines of V79, L929, and Balb/3T3 cells, the cytotoxicity of the dithiocarbamates and the SRM films were compared by agar diffusion assay, filter diffusion assay, neutral red assay, cell growth assay, and colony assay. Among these in vitro cytotoxicity tests, colony assay was found to be the most sensitive method for detecting the cytotoxicity. The cytotoxic potentials of extracts from SRM films correlated well with the concentrations of ZDEC or ZDBC involved in SRM. When various rubber materials including SRM and surgical rubber latex materials were tested, cytotoxic potentials of these extracts were also correlated with the inflammatory tissue capsule thickness in short-term implantation tests. On the basis of these results, the SRM is judged to be useful for validating test sensitivity, and comparing the correlation between in vitro and in vivo responses.

3T3 Cells↗

A proposal for a standard reference artificial urine in in vitro urolithiasis experiments.

We propose that in vitro urolithiasis research that involves crystallization should include in each observation set measurements made in a standard reference artificial urine to facilitate comparison of work done in different laboratories and facilitate the rate of advance in urolithiasis research. We describe a general technique to construct artificial urine and apply it to the construction of the reference artificial urine that we propose.

Crystallization↗

[Glycyrrhitinic acid reference standard (Control 941) of the National Institute of Health Sciences].

The raw material of glycyrrhitinic acid was examined for preparation of the "Glycyrrhitinic Acid Reference Standard". The candidate material was evaluated physico-chemically by a collaborative study in which five laboratories participated. Analytical data obtained were as follows: UV spectrum, lambda max = 251 nm and specific absorbance E1%1cm (EtOH) at the lambda max = 145; IR spectrum, specific absorption numbers were at 1719, 1654, 1216, and 1170 cm-1; thin-layer chromatography, some laboratories detected a trace amount of one spot and others not detected; high-performance liquid chromatography, 2-6 impurities were detected and the amount of any impurities were estimated to be less than 0.2% and the total amount less than 0.5%. Based on the above results, the candidate material was authorized as the Glycyrrhitinic Acid Reference Standard of National Institute of Health Sciences.

Chromatography, High Pressure Liquid↗

A Standard Reference Material to determine the sensitivity of techniques for detecting low-frequency mutations, SNPs, and heteroplasmies in mitochondrial DNA.

Human mitochondrial DNA (mtDNA) mutations are important for forensic identifications and mitochondrial disease diagnostics. Low-frequency mutations, heteroplasmies, or SNPs scattered throughout the DNA in the presence of a majority of mtDNA with the Cambridge Reference Sequence (CRS) are almost impossible to detect. Therefore, the National Institute of Science and Technology has developed heteroplasmic human mtDNA Standard Reference Material (SRM) 2394 to allow scientists to determine their sensitivity in detecting such differences. SRM 2394 is composed of mixtures ranging from 1/99 to 50/50 of two 285-bp PCR products from two cell lines that differ at one nucleotide position. Twelve laboratories using various mutation detection methods participated in a blind interlaboratory evaluation of a prototype of SRM 2394. Most of these procedures were unable to detect the mutation when present below 20%, an indication that, in many real-life cases, low-frequency mutations remain undetected and that more sensitive mutation detection techniques are urgently needed.

Cells, Cultured↗