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Systolic hypertension and the response to blunt trauma in infants and children.

OBJECTIVES: To describe age-related systolic blood pressures and pulse rates in children following blunt injury. To compare these variables with standard reference values for uninjured children at rest and with reference ranges from the Advanced Paediatric Life Support (APLS) guidelines. DESIGN: Secondary analysis of a prospective cohort. SETTING: Emergency departments throughout England and Wales. PARTICIPANTS: 12906 children presenting with acute blunt traumatic injury from August 1989 to September 1998. MAIN OUTCOME MEASURES: Systolic blood pressure and pulse rate on arrival. RESULTS: Injured children had higher systolic blood pressures than the standard quoted 'norms'. Standard reference values of systolic blood pressure for children at rest always appeared below the 50th percentile for our cohort of injured children (range 7th-27th percentiles). Pulse rates for children at rest were always towards the mid-range for injured children (range 41st-54th percentiles). These results appeared unrelated to injury severity. Age related APLS reference ranges for systolic blood pressure and pulse rate resembled the standard reference values for uninjured children at rest. CONCLUSIONS: Injured children have a relative systolic hypertension compared with children at rest. Pulse rates in the two groups are comparable. Following injury, children with apparently 'normal' age-specific systolic blood pressures on arrival in the Emergency Department are relatively hypotensive and should be carefully assessed.

Adolescent↗

[Evaluation on analysis of six minerals in ten biologic materials].

The study is to evaluate the content of Mn, Cu, Fe, Zn, Mg and Ca in 10 sorts of biological material. The standard methods (GB/T5009.13,14,90,92 - 2003) were taken to measure. Two standard reference materials were used to control the accuracy of analyses. And chemical uncertainty was used to evaluate 6 minerals content. The results described the six minerals contents for the ten biologic materials. The study provided the necessity conditions to be used as standard reference materials for these 10 biological materials.

Calcium↗

Simultaneous mass bias and fractionation corrections utilizing isotopic solid standards and laser ablation ICPMS.

Homogeneous incorporation of analytes of known isotopic abundance into sol-gel-derived standards that mimic important mineral systems has the potential to contribute significantly to providing solid standard benchmarks for a range of applications. This preliminary study reports on the synthesis of solid glass standards produced via the sol-gel method and their doping with Standard Reference Material (SRM) 981 Common Lead Isotopic Standard and SRM 982 Equal-Atom Lead Isotopic Standard. Custom isotopic materials were also prepared using mixtures of the two isotopic SRMs. Particles from these solid samples were then introduced into an inductively coupled plasma mass spectrometer via laser ablation to determine whether materials of suitable homogeneity could be developed as isotopic reference materials. Preliminary results for Pb isotope ratios show that these solid isotopic reference standards are capable of correcting for instrumental mass bias and laser ablation-induced bias due to fractionation simultaneously. Correction factors generated from the quotient of the certified and measured Pb isotopic ratios in sol-gel disks spiked with SRMs 981 and 982 were successfully applied to produce accurate isotope ratios using comparative control/unknown checks. These correction factors were also used to assign Pb isotopic ratios in NIST SRM 612 Trace Elements in Glass that were in excellent agreement with published measurements, suggesting that tunable matrix sol-gel disks can serve as adequate control matrixes for evaluation of isotope ratios in glass samples.

Journal Article↗

Follicle stimulating hormone international standards and reference preparations for the calibration of immunoassays and bioassays.

Follicle stimulating hormone is a dimeric glycoprotein hormone which is used widely in reproductive and developmental medicine both as a diagnostic analyte and as a therapeutic product. It is therefore a good example of a clinically important heterogeneous material for which a number of different assay methodologies have been developed. Immunoassays for follicle stimulating hormone (FSH) are used in the diagnosis of disorders of reproduction and development, whereas in vivo bioassays are used for calibration of therapeutic preparations. Different immunoassay systems, based on different formats, exhibit variability in their estimates of activity of FSH which arises from different specificities of antibodies for different forms of FSH which are encountered. In order to minimise between assay variation and to enable better between laboratory comparisons the World Health Organisation (WHO) has issued a series of ampouled preparations of FSH. The availability of these materials has been reviewed previously but on the completion of a recent collaborative study to evaluate candidate standards for rDNA-derived FSH and highly purified urinary FSH (urofollitropin) it is now appropriate to review the current status of these standards and to discuss the future of standardisation for FSH in particular and where appropriate to make reference to other materials.

Animals↗

Validation of the anthrax lethal toxin neutralization assay.

A validation of the performance characteristics of a toxin neutralization assay is presented. This in vitro assay measures the functional ability of antisera, containing antibodies to anthrax lethal toxin, to specifically protect J774A.1 cells against Bacillus anthracis lethal toxin cytotoxicity. This colormetric assay is based upon the reduction of MTT by living cells. Human and rabbit antisera produced against anthrax vaccine absorbed (AVA) were used to validate the assay. Results showed a high level of repeatability and reproducibility, particularly for a bio-assay. Inter-assay variability in absorbance values was the most prominent negative finding however, an acceptable level was demonstrated with a ratio [neutralization ratio (NR)] of the test serum 50% effective dose (ED(50)) to the reference standard ED(50). Accuracy was maintained, even in samples with minimal neutralizing capacity, and linearity was noted when sample dilutions resulted in accurate prediction of the Y(max)and Y(min). Specificity tests demonstrated that normal sera did not have an observable effect on the ability of the reference standard to neutralize toxin. The assay remained stable against time, temperature, and freeze/thaw effects on the reference standards, but not on the toxin. The assay also remained stable against media and solution storage effects. Cell passage number and cell plating density were two critical parameters identified during the robustness studies that may be responsible for inter-assay variability in absorbance values. The work was performed in accordance with the FDA's Bioanalytical Method Validation Guidance for Industry and the FDA's Good Laboratory Practice for Nonclinical Laboratory Studies (21 CFR Part 58).

Animals↗

Calibration of [123I]iodine-labeled tissue standards for autoradiographic studies.

Autoradiographic images can be analyzed with computer-assisted microdensitometry relative to radioactive reference standards to provide quantitative measurements of regional radioactivity concentrations. [123I]Iodine containing sections of brain paste have been calibrated relative to plastic-embedded tritium(3H) and 125Iodine standards. For exposure times of 8, 12 and 24 h, plastic-embedded standards covered a range concentrations of [123I]iodine from 1000 to 100,000 dpm/mg wet weight. Iodine-123 radioactivity was linear with section thickness from 5 to 30 microns. These studies confirmed the feasibility of using commercially available longer-lived reference standards to provide [123I]iodine equivalent values in absolute units of dpm (or microCi) per mg tissue.

Animals↗

Microencapsulated ferrous sulfate to fortify cow milk: absorption and distribution in mice.

To determine the absorption and biodistribution of iron from microencapsulated ferrous sulfate (SFE-171), used to fortify dairy products with iron, a comparative study in four groups of 30 mice each was carried out. In two of the groups, the absorption of iron from ferrous ascorbate in water (13.3 +/- 4.3%) and from ferrous sulfate in water (12.7 +/- 3.9%) was determined and taken as reference standards. In the third group the iron absorption from SFE-171 in milk was determined, giving a value of 12.1 +/- 4.2%, which statistically does not differ from the data obtained with either reference standard. In the fourth group, the absorption of iron from ferrous sulfate in milk showed a value of 7.7 +/- 3.4%, which statistically differs with a p < 0.01 from the data corresponding to the other three groups. The biodistribution studies showed that the iron from the SFE-171 follows the same metabolic pathway as the iron from the reference standards thus, giving a higher radioactivity percentage and radioactivity concentration in organs or systems, principally blood, that are closely related to iron metabolism. Our studies allow us to conclude that the iron from SFE-171 in milk follows the same behavior as the nonhemic iron, with a higher absorption than that of ferrous sulfate in milk.

Absorption↗

A comparative study of clinical management strategies for vaginal discharge in family planning and genitourinary medicine settings.

OBJECTIVE: To compare strategies for management of women with vaginal discharge in genitourinary medicine (GUM) and family planning (FP) settings. METHODS: The setting was a centre housing both FP and GUM departments within a primary care trust in Scotland. The study participants were 200 women presenting with vaginal discharge. A randomised, controlled, crossover design was employed. Strategies typical of FP and GUM were performed on every participant in a randomised sequence. Day 1 diagnoses were made by the FP strategy (history and examination) and the GUM strategy (nearpatient microscopy added). Day 7 results were obtained from final analysis of all specimens. Days 1 and 7 results were compared with the reference standard provided by all the test results. The main outcome measures were incorrect diagnoses on Days 1 and 7. RESULTS: On Day 1 the FP strategy resulted in significantly more incorrect diagnoses than the GUM strategy when compared with the reference standard (73 vs 32; p <0.001). On Day 7 the GUM strategy resulted in significantly more incorrect diagnoses than the FP strategy when compared with the reference standard (32 vs 17; p = 0.019). CONCLUSIONS: Vaginal discharge can be managed effectively in community settings such as FP and primary care. The addition of near-patient microscopy produces a more accurate immediate diagnosis. The addition of a high vaginal swab for culture produces a more accurate final diagnosis. The costs of on-site microscopy must be considered.

Adolescent↗

[Allergy to cypress pollen: preparation of a reference and standardization extract in vivo].

Development of Cypress allergy frequency led to the standardization of commercial cypress extract used for diagnosis and immunotherapy. Previous in vitro studies on two cypress pollen species (Cupressus sempervirens and Cupressus arizonica) allowed us to produce an allergenic solution composed by a mixture of both extracts for in vivo standardization. Dilutions of this allergenic solution were tested by prick-test on 44 patients with clinical allergy to cypress pollen to define the dilution that corresponds to a 6 mm wheal conformed to the definition of 100 IR. The mixture of the two major species found in France is justified by the in vitro study results. Extracts revealed complementary allergenic composition: Cup sempervirens showed a wider diversity of allergens whereas Cup arizonica showed a higher content of the major 43 kDa allergen. Thus, according to in vivo analysis, we are able to produce a standardized extract of Cypress pollen expressed in IR.

Adult↗

Pulmonary function in normal south Indian children aged 7 to 19 years.

There are only a few studies that have established reference standards for pulmonary function of Indian children. Reference standards for pulmonary function that are reported for Indian children are mainly from northern and western parts of the country and there is a paucity of data on pulmonary function in normal South Indian children. Therefore, pulmonary function tests (spirometry and maximal expiratory flow rates) were carried out in 469 South Indian healthy children (246 boys and 223 girls) between 7-19 years of age to derive regression equations to predict pulmonary function. The correlations of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were, in general highest with height followed by weight and age. Peak expiratory flow rate (PEFR), forced mid-expiratory flow (FMF) and forced expiratory flow rates at 25%, 50% and 75% of FVC (FEF25% FVC, FEF50%FVC and FEF75%FVC) were also significantly correlated with physical characteristics (age, height and weight). With a view to find out regression equations to predict spirometric functions based on physical characteristics (age, height and/or weight), the functions were regressed over all possible combinations of regressor variables, i.e. age, height and weight separately for boys and girls. The height influences the prediction equation in males to a great extent, whereas age and weight had greater influence in girls. Regression equations were derived for boys and girls for predicting normal pulmonary functions for children in South India. The pulmonary function measurements in South Indian children were similar to those reported for subjects from Western India and lower than those reported for Caucasians.

Adolescent↗

Biological value of bone-precipitated dicalcium phosphate in turkey starter diets.

A study was conducted to determine the relative biological value (RBV) of phosphorus from two bone-precipitated dicalcium phosphates (DCP-BP) in turkey starter diets. An estimated 40,000 metric tons of DCP-BP are produced annually in the United States as a by-product of gelatin production. The two DCP-BP sources were compared to commercial feed phosphates. Two bioassay experiments of 21-d duration were conducted with female turkeys. Phosphate sources were each fed at three levels (.18, .24, and .36% added total phosphorus) in a corn-soybean meal diet. Calcium level was maintained constant at 1.0% in all diets by adjusting the level of ground limestone. Four replicate pens of six poults were randomly assigned at 1 d of age to each level of each phosphorus source in each bioassay. The reference standard was United States Pharmacopeia (USP) grade calcium phosphate, dibasic dihydrate. Data representing three response criteria (weight gain, gain:feed ratio, and tibia ash percentage at 21 d) were combined to calculate a biological value (BV) for each test source and the reference standard phosphate. A RBV was then computed for each test source. The RBV of the two DCP-BP sources were 98.8 and 99.1, as compared to 100.0 for the reference standard, and 86.7, 87.1, and 88.4 for three commercial, thermochemically produced defluorinated phosphates. The RBV of one commercial mono-dicalcium phosphate, and three di-monocalcium phosphates were: 96.4, and 91.2, 94.7, and 101.5, respectively. The two DCP-BP sources compared favorably to commercial feed phosphates, and would be satisfactory supplements in diets for starting chicks, poults, pigs, and other species.

Animal Feed↗

Diagnosis of Hirschsprung's disease: a prospective, comparative accuracy study of common tests.

OBJECTIVE: To compare the diagnostic accuracy of contrast enema (CE), anorectal manometry (ARM), and rectal suction biopsy (RSB) for the detection of Hirschsprung's disease (HD). STUDY DESIGN: Following a prospective protocol, infants suspected of HD underwent all 3 index tests. Children with positive results on 2 or more index tests or who continued to have severe bowel problems underwent a full thickness biopsy as reference standard. Clinical follow-up was the reference standard in all other children. RESULTS: Between 2000 and 2003, 111 consecutive patients (67 boys; median age, 5.3 months) in whom HD was suspected were enrolled. HD was found in 28 patients. RSB had the highest sensitivity (93%) and specificity (100%) rates, but values were not significantly different from CE (sensitivity, 76%; specificity, 97%) or from ARM (sensitivity, 83%; specificity, 93%). Inconclusive test results occurred in 8 infants with CE, in 15 infants with ARM because of agitation, and in 2 infants with RSB. CONCLUSION: RSB is the most accurate test for diagnosing HD, and it has the lowest rate of inconclusive test results.

Anal Canal↗

Meta-analysis: The value of clinical assessment in the diagnosis of deep venous thrombosis.

BACKGROUND: Clinical assessment of suspected deep venous thrombosis (DVT) should be based on systematically evaluated evidence. PURPOSE: To determine whether clinical findings, risk scores, and physicians' empirical judgments affect the likelihood of detecting DVT on definitive testing. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, ACP Journal Club, and citation lists (1966 to January 2005). STUDY SELECTION: Cohort studies published in English, French, Spanish, or Italian that compared clinical assessment with a reference standard. DATA EXTRACTION: The authors extracted standardized data, including setting, exclusions, population characteristics, reference standard, and results, and assessed quality against validated criteria. DATA SYNTHESIS: The authors combined data by using random-effects meta-analysis and, if appropriate, used meta-regression to identify covariates that predicted diagnostic accuracy. Only malignancy (likelihood ratio [LR], 2.71), previous DVT (LR, 2.25), recent immobilization (LR, 1.98), difference in calf diameter (LR, 1.80), and recent surgery (LR, 1.76) were useful for ruling in DVT, while only absence of calf swelling (LR, 0.67) or difference in calf diameter (LR, 0.57) was useful for ruling out DVT. The Wells clinical score was more valuable than the individual characteristics; it stratified patients into groups with high (LR, 5.2), intermediate, and low (LR, 0.25) probability of DVT. The Wells score seemed able to stratify patients by risk only for proximal DVT, and it performed better in cohorts that were younger or excluded patients with previous thromboembolism. LIMITATIONS: Pooled estimates were subject to substantial heterogeneity. This may limit extrapolation between observers and settings. Only published studies were included, so findings may be subject to publication bias. CONCLUSION: Individual clinical features are of limited value in diagnosing DVT. Overall assessment of clinical probability by using the Wells score is more useful.

Humans↗

Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics.

BACKGROUND: A response to proton-pump inhibitors (PPIs) is commonly considered to support the diagnosis of gastroesophageal reflux disease (GERD). However, the accuracy of this diagnostic strategy has not been well established. OBJECTIVE: To estimate the diagnostic test characteristics of successful PPI treatment with objective measures of GERD by performing a meta-analysis based on the published literature. DATA SOURCES: English-language studies were identified by searching the Cochrane Clinical Trial Register and MEDLINE from 1 January 1980 through 1 July 2003. STUDY SELECTION: Studies in which the clinical response to a short course (1 to 4 weeks) of normal- or high-dose PPI therapy could be compared with objective measures of GERD (24-hour pH monitoring, endoscopy findings, symptom questionnaires). DATA EXTRACTION: Studies were screened for inclusion by 1 author. Final decisions on exclusion were made by consensus with 2 of the other authors. Two investigators independently extracted the data. Information extracted included patient characteristics, study design, setting, specific type and dose of medication, duration of treatment, and definitions of outcomes. DATA SYNTHESIS: Sensitivity and specificity were determined by comparing a clinical response to PPIs with objective measures for GERD. The summary receiver-operating characteristic curve method was used to summarize test characteristics across studies. Sensitivity and specificity were also combined independently by using a random-effects model. Fifteen studies met the inclusion criteria and provided sufficient data. With 24-hour pH monitoring as the reference standard, the positive likelihood ratio ranged from 1.63 to 1.87, and combined estimates of sensitivity and specificity were 0.78 (95% CI, 0.66 to 0.86) and 0.54 (CI, 0.44 to 0.65), respectively. These values were lower with the other reference standards. LIMITATIONS: Data were insufficient to determine the effect of various doses of PPIs and duration of therapy on test characteristics. CONCLUSION: Successful short-term treatment with a PPI in patients suspected of having GERD does not confidently establish the diagnosis when GERD is defined by currently accepted reference standards.

Adult↗

Site of protein digestion in steers: predictability.

The nature and predictability of protein digestion in steers were examined in a series of experiments. Bypass and intestinal digestion of supplemental proteins were measured with Angus steers (203 to 254 kg) fitted with dual reentrant intestinal cannulas. Daily feed intakes were 1.8 to 1.9% of body weight. Two trials were conducted with soybean meal, cottonseed meal, a hardened casein, meat meal and two different sources of dehydrated alfalfa meal fed with an 80% concentrate diet. In the third trial, digestion of soybean meal and cottonseed meal were measured with a 60% prairie hay diet. Estimates of ruminal escape or bypass were 43, 50, 36, 76, 57, 62, 24 and 43%, respectively. Results suggest that roughage level alters bypass. A standard reference system for predicting bypass based on measurements of N solubility and in situ disappearance rates was compared with measured bypass. The correlation between observed bypass to the small intestine and bypass predicted by this system was high (r = .91, P less than .01). Combining pepsin solubility, an indicator of true intestinal digestibility, with bypass estimated by the standard reference system, allowed us to predict N disappearance from the small intestine. Predicted and measured N disappearance of fed N from the small intestine were very close.

Animals↗

The effectiveness of screening for diabetic retinopathy by digital imaging photography and technician ophthalmoscopy.

AIMS: To evaluate the introduction of a community-based non-mydriatic and mydriatic digital photographic screening programme by measuring the sensitivity and specificity compared with a reference standard and assessing the added value of technician direct ophthalmoscopy. METHODS: Study patients had one-field, non-mydriatic, 45 degrees digital imaging photography prior to mydriatic two-field digital imaging photography followed by technician ophthalmoscopy. Of these patients, 1549 were then examined by an experienced ophthalmologist using slit lamp biomicroscopy as a reference standard. The setting was general practices in Gloucestershire. Patients were selected by randomizing groups of patients (from within individual general practices) and 3611 patients were included in the study. Patients for reference standard examination were recruited from groups of patients on days when the ophthalmologist was able to attend. The main outcome measure was detection of referable diabetic retinopathy (DR) as defined by the Gloucestershire adaptation of the European Working Party guidelines. RESULTS: For mydriatic digital photography, the sensitivity was 87.8%, specificity was 86.1% and technical failure rate was 3.7%. Technician ophthalmoscopy did not alter these figures. For non-mydriatic photography, the sensitivity was 86.0%, specificity was 76.7% and technical failure rate was 19.7%. CONCLUSIONS: Two-field mydriatic digital photography is an effective method of screening for referable diabetic retinopathy. Non-mydriatic digital photography has an unacceptable technical failure rate and low specificity.

Adolescent↗

Minimally invasive nephron-sparing surgery (MINSS) for renal tumours part I: laparoscopic partial nephrectomy.

OBJECTIVES: To review the evolution and current status of extirpative methods (laparoscopic partial nephrectomy [LPN]) of minimally invasive nephron-sparing surgery (MINSS) for renal tumors. METHODS: The English language literature of the past 10 yr was reviewed by using the National Library of Medicine database and the following keywords: kidney, laparoscopic partial nephrectomy, minimally invasive, nephron-sparing surgery, renal, and tumor. Over 275 papers were identified. Of these, 55 papers were selected for this review on the basis of their contribution in advancing the field with regards to (1) evolution of concepts, (2) development and refinement of techniques, and (3) intermediate- and long-term clinical outcomes of LPN. RESULTS: Open partial nephrectomy (OPN) is the reference standard for nephron-sparing surgery against which all MINSS techniques should be measured. With available skills for time-sensitive intracorporeal suturing, LPN provides perioperative results and long-term oncologic and functional outcomes comparable to the reference standard, with significantly decreased patient morbidity. The initial 5-yr data of 50 patients has just become available, and shows overall and cancer-specific survival of 84% and 100%, respectively. As global experience with this technique increases, data need to be prospectively accrued, and long-term cancer cure rates should be compared with the reference standard. CONCLUSIONS: As of this writing, the technique and global acceptance of LPN is evolving, although it remains restricted by the complexity of laparoscopic renal reconstruction. In expert hands, cancer cure and renal function outcomes are similar to OPN.

Humans↗

Digital imaging in differential diagnosis of small choroidal melanoma.

BACKGROUND: To assess the role of digital imaging and a new subtraction method for differential diagnosis of choroidal nevus and small choroidal melanoma. METHODS: Of 241 consecutive patients referred to a tertiary referral center for suspected choroidal melanoma, 110 who underwent digital imaging of the ocular fundus were eligible for this study. Digital color, red-free and red light retinal images were evaluated in a randomized and masked manner and by the subtraction method for diagnosis of the fundus lesion. The reference standard was based on the combined results of ophthalmological examination, including mydriatic ophthalmoscopy, B scan ultrasonography, digital imaging and fluorescein angiography of the ocular fundus. RESULTS: Comparative use of digital color, red-free and red light imaging had 85.7% (95%CI 42.1-99.6) sensitivity, 99.0% (95%CI 94.7-99.9) specificity and 98.2% (95%CI 93.6-99.8) exact agreement versus reference standard in differentiation of small choroidal melanoma from pseudomelanoma. Direct comparison between use of digital images and the reference standard showed excellent agreement in detecting small choroidal melanoma from suspected choroidal lesions (K 0.847; 95%CI 0.639-1.0). The subtraction method was useful to show growth in four of 94 melanocytic choroidal tumors. The mean annual incidence of choroidal melanoma in Southwest Finland was 0.80 per 100.000 population. The most frequent choroidal pseudomelanomas were choroidal melanotic and amelanotic nevi, disciform lesions, congenital hypertrophy of the retinal pigment epithelium, and circumscribed choroidal hemangioma. CONCLUSIONS: Combined use of digital color, red-free and red light imaging was a suitable adjunct in differentiation of small choroidal melanoma from different pseudomelanomas. The subtraction method may reveal early growth of the melanotic choroidal tumors.

Adolescent↗