Discrepancies in hFSH measurements by two-site IRMA in the ovulatory phase of the menstrual cycle.
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Biomedical subjects
Publications and source records attributed to R S Chapman.
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OBJECTIVES: Infants from families of low socioeconomic status are said to suffer higher rates of lower respiratory illness, but this assertion has not been carefully examined. METHODS: We studied the frequency and determinants of lower respiratory illness in infants of different socioeconomic status (n = 393) by analyzing data from a community-based cohort study of respiratory illness during the first year of life in central North Carolina. RESULTS: The incidence of lower respiratory illness was 1.41 in the low socioeconomic group, 1.26 in the middle group, and 0.67 in the high group. The prevalence of persistent respiratory symptoms was 39% in infants in the low socioeconomic group, 24% in infants in the middle group, and 14% in infants in the high group. The odds of persistent respiratory symptoms in infants of low and middle socioeconomic status were reduced after controlling for environmental risk factors for lower respiratory illness. Enrollment in day care was associated with an increased risk of persistent symptoms among infants of high but not low socioeconomic status. CONCLUSIONS: Infants of low socioeconomic status are at increased risk of persistent respiratory symptoms. This risk can be partly attributed to environmental exposures, most of which could be changed.
Monoclonal antibodies to the biologically active N terminal region of parathyroid hormone (PTH) suitable for use in the measurement of circulating PTH concentrations have proved difficult to produce. In this study, no serum PTH antibody titres could be detected in mice using synthetic human PTH (1-34) (free or coupled to albumin) or PTH (1-10) (coupled to keyhole limpet haemocyanin) as immunogen. A consistent response to PTH (1-34) peptide was obtained in DA rats. We have produced five monoclonal antibodies to PTH (1-34) derived from the fusion of DA rat spleen cells and the mouse myeloma line X63 Ag.8.653. Bulk production of the antibodies was achieved using congenitally athymic mice for ascites production. Antibody assessment studies revealed the antibodies to be sensitive to the oxidation state of the methionine residues in PTH (1-34). Two of the antibodies, 3B3 and 6E3, were shown to be of potential use in measuring circulating PTH (1-84) when used in combination with available antibodies to C terminal PTH. A third antibody, 4G3, which failed to recognise PTH (1-84) when used in combination with 3B3, formed the basis of a specific assay for PTH (1-34).
We describe a case of papuloerythroderma. This is a distinctive clinical entity characterized by pruritus, red-brown flat-topped papules exhibiting the "deck-chair" sign, eosinophilia, and lymphopenia. We propose that the Langerhans cell may have a central role in the pathogenesis of papuloerthroderma and we describe an excellent response to photochemotherapy.
This study investigates the development of vocabulary and syntax comprehension skills cross-sectionally in 48 children and adolescents with Down syndrome (Trisomy 21), aged 5-20 years, in comparison to 48 control children aged 2-6 years matched statistically for nonverbal mental age and mother's years of education. Age-equivalent scores on vocabulary (PPVT-R) and syntax (TACL-R) comprehension tests differed in the Down syndrome group but not the control group; vocabulary comprehension was relatively more advanced than syntax. Age-equivalent scores on nonverbal cognitive subtests of pattern analysis and short-term memory for bead arrangements (Stanford-Binet, 4th ed.) also differed for the Down syndrome group but not the control group, indicating an unusual pattern of nonverbal cognitive function in the Down syndrome group. Stepwise multiple regression analyses showed that chronological age and mean mental age, collectively, accounted for 78% of the variability in vocabulary comprehension and 80% of the variability in syntax comprehension in the Down syndrome group, with total passes on a hearing screening accounting for an additional 4% in each case. Implications for research are discussed.
In Xuanwei County, Yunnan Province, lung cancer mortality rates are among the highest in China in both males and females. Previous studies have shown a strong association of lung cancer mortality with indoor air pollution from 'smoky' coal combustion. In the present case-control study, 110 newly-diagnosed lung cancer patients and 426 controls were matched with respect to age, sex, occupation (all subjects were farmers), and village of residence (which provided matching with respect to fuel use). This design allowed assessment of known and suspected lung cancer risk factors other than those mentioned above. Data from males and females were analysed by conditional logistic regression. In females who do not smoke, the presence of lung cancer was statistically significantly associated with chronic bronchitis (odds ratio [OR] = 7.37, 95% confidence interval [Cl]: 2.40-22.66) and family history of lung cancer (OR 4.18, 95% Cl: 1.61-10.85). Females' results also suggested an association of lung cancer with duration of cooking food (OR 1.00, 9.18 and 14.70), but not with passive smoking (OR 0.77, 95% Cl: 0.30-1.96). In males, lung cancer was significantly associated with chronic bronchitis (OR 7.32, 95% Cl: 2.66-20.18), family history of lung cancer (OR 3.79, 95% Cl: 1.70-8.42), and personal history of cooking food (OR 3.36, 95% Cl: 1.27-8.88). In males a dose-response relationship of lung cancer with smoking index (years of smoking*amount of smoking) was shown by risks of 1.00, 2.61, 2.17 and 4.70.
The assessment of specificity in two-site immunometric assays is complex. Conventional approaches based on standard substitution with cross-reactant may yield misleading results. An 'in-house' immunoradiometric assay (IRMA) for human growth hormone (hGH) appeared free from cross-reactivity with human placental lactogen (hPL) in a single point standard substitution experiment performed by the United Kingdom External Quality Assessment Scheme (UK EQAS). However, detailed studies based on the substitution of hGH standards with hPL cross-reactant, the addition of hPL cross-reactant to hGH standards and the recovery of added hGH from endogenous cross-reactant (sera from pregnant subjects) revealed gross cross-reactivity of hPL in the hGH assay. We recommend that the validation of assay specificity should require the demonstration of quantitative recovery of a range of analyte concentrations from human sera that contain varying endogenous concentrations of cross-reactant.
We report the development of a two-site immunoradiometric assay for PTH(1-84) based on two site-specific monoclonal antibodies--3B3 (radiolabelled antibody) specific for PTH(1-34) and ESQ1 (on solid phase) specific for PTH(74-84). Antibody 3B3 is sensitive to the oxidation of the methionine residues in PTH(1-34) therefore hydrogen peroxide (0.1 M) is added to the incubation mixture. Validation studies confirm quantitative recovery of both oxidized and reduced PTH(1-84). The assay has a minimum detection limit of 0.5 pmol/L and a range of 1.5-250 pmol/L with an intra-assay CV of less than 10% (2.8-250 pmol/L less than 5% CV). Studies on clinical samples indicate good discrimination between normal subjects (mean 2.21; range 1.0-5.0 pmol/L) and patients with primary hyperparathyroidism (mean 21.0; range 5.8-100 pmol/L) who in turn are well separated from patients with hypercalcaemia of malignancy (14/18 less than 0.5 pmol/L).
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In Xuan Wei County, Yunnan Province, lung cancer mortality rates are among China's highest in males and females. Previous studies have shown a strong association of lung cancer mortality with air pollution from "smoky" coal combustion. In the present quantitative risk assessment of indoor air pollution study, the result strongly shows an obvious on-site exposure-response relationship between benzo[a]pyrene concentration in indoor air and lung cancer mortality and strongly supports the hypothesis that indoor air pollution is the main risk factor in inducing lung cancer in Xuan Wei County. In the present case-control study, the result shows that in females, the presence of lung cancer is statistically significantly associated with chronic bronchitis and family history of lung cancer. The results also suggest an association of lung cancer with duration of cooking food, but not with passive smoking. In males, the presence of lung cancer is associated with smoking, bronchitis, family history of lung cancer, and personal history of cooking food.
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Fast mapping of novel words for objects was compared in 48 children and adolescents with Down syndrome (ages 5:6-20:6), who were delayed in expressive language acquisition compared to mental age, and 48 normally developing children matched for mental age (chronological ages 2:0-6:0). Normal and Down syndrome groups did not differ in their ability to infer a connection between the novel word and referent (100% vs. 100%), to comprehend the novel word after a single exposure (83% vs. 73%), and to recall the location in which they hid the novel referent (83% vs. 75%). Nor did they differ in their ability to produce the novel word correctly (at least two out of three phonemes in order: 48% vs. 40%). When retested after an hour of other activity, only the production task showed a significant, and comparable, decrement. Comparing youngest and oldest quarters of each group showed improved memory for location in both, improved comprehension in the Down syndrome group, and improved production in the control group. Adults (n = 12), in contrast, performed perfectly on all tasks except the delayed word production. Neither intelligibility differences nor use of real word labels accounts for the failure to find a difference between groups. Fast mapping skills were unrelated to expressive language deficit in these children with Down syndrome.
Affinity purification of antibody before covalent binding to pre-activated micro-particles (Dynospheres) was necessary to overcome the reduced coupling capacity evident with low titre antisera, particularly antihapten sera. Optimally prepared Dynospheres anti-thyroxine provided a radioimmunoassay with good performance and economical usage of microparticles. Assay sensitivity was less than 10 nmol/l while precision across the clinically relevant dose range (50-150 nmol/l) was 3% CV using 125 micrograms particles per assay tube.
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The usual method for calculation of the "sensitivity" of thyrotropin immunometric assays is multireplicate analysis of the zero analyte standard. Although this is a statistically valid estimate of the scatter likely to be found in the response variable, it is unrelated to normal analytical practice (usually analysis in duplicate) and estimates intra-assay errors only. This study was designed to assess the analytical performance of 10 immunometric assays used routinely for measurement of thyrotropin in human serum. Response data from each assay were accumulated to provide (a) an estimate of "sensitivity" from multireplicate analysis and (b) an estimate of "minimum detection limit," relating directly to errors associated with routine performance and derived from a minimum of 500 duplicate analyses. We conclude that the "minimum detection limit" should be promoted as a more meaningful measure of assay performance at low analyte concentrations than the "sensitivity" derived from multireplicate analysis of the zero-analyte standard.
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