Creatinine related reference ranges for urinary homovanillic acid and vanillylmandelic acid at 6 months of age

The relationship between homovanillic acid (HVA), vanillylmandelic acid (VMA), and creatinine in the urine of 6 month old babies has been studied and reference ranges in the form of centiles constructed for HVA and VMA against creatinine. Over 10,000 urine samples were collected from babies in four health districts in the north of England. HVA and VMA concentration, either independently or when divided by creatinine concentration, were dependent upon the absolute concentration of creatinine in the sample. After adjustment for creatinine significant differences in the mean concentration of HVA were found between sexes. No such differences were found for VMA. HVA and VMA were also found to be age dependent. Centiles were constructed using a procedure which makes no distributional assumptions about the data. The net effect of utilising these centiles was to increase the predictive value of a positive screening test from 20% to 40% without any increase in the false negative rate.     

Computer graphics for digitally formatted images

The increasing use of digitally formatted imaging systems requires high-quality interactive gray-scale computer raster graphics systems for the management, display, and analog film recording of digital image and alphanumeric information. These systems are a combination of computer hardware and software and implement a set of graphics protocols. This paper describes a set of interactive graphics protocols that has been developed for clinical use.     

Radiographic abnormalities and duration of employment in Western Australian iron-ore miners

Plain chest radiographs of 788 Pilbara iron-ore miners from Western Australia have been examined by two independent observers for evidence of pneumoconiosis. The prevalence of any radiographic abnormality (a profusion grade of 0/1 or greater on the International Labour Office [ILO] scale) was 6.7% for Reader 1 and 9.9% for Reader 2. The prevalence of a definite radiographic abnormality (a profusion grade of 1/0 or greater on the ILO scale) was 1.9% for Reader 1 and 2.8% for Reader 2. The prevalence of any abnormality, as identified by either or by both observers, was significantly related to age. The relationship between a radiographic abnormality and the duration of employment was less clear. The results indicate a need for more detailed and comprehensive studies of the effects of iron-ore dust in this industry.     

Peripheral pooling of bronchographic contrast material: evidence of its relationship to smoking and emphysema.

Sixty-six subjects, mainly derived from various occupational groups and one-third of whom admitted to dyspnoea on exertion, have been grouped according to the appearance of their peripheral airways at bronchography with oily propyliodone. Eleven subjects showed marked peripheral pooling of radiographic contrast material, 22 showed mild or moderate pooling, and in 33 peripheral pools were absent. Pooling was not seen in non-smoking subjects. In the group of subjects without pooling, pulmonary function in non-smokers and subjects with a history of smoking was similar. Subjects with marked pooling had a significantly lower pulmonary diffusing capacity (transfer factor) and evidence of loss of pulmonary elastic recoil when compared with subjects with absent peripheral pooling. These results indicate that bronchographic peripheral pooling is associated with the physiological changes of panacinar pulmonary emphysema and suggest that a causal relationship may exist between the organic bronchiolar lesion of pooling and the peripheral parenchymal lesion of panacinar emphysema.     

Respiratory symptoms and lung-function changes with exposure to five substances in aluminium smelters

OBJECTIVES: To determine whether exposure to five different occupational substances contributes to respiratory symptoms in aluminium smelter workers. METHODS: A cross-sectional survey of 1,615 male employees of two Australian aluminium smelters was conducted in 1995. Subjects underwent spirometry and were asked about respiratory symptoms and the relationship of those symptoms to work. Their job histories were combined with a task exposure matrix to produce individual quantitative measures of cumulative exposure to fluoride, sulphur dioxide, inspirable dust, the benzene-soluble fraction of coal tar pitch volatiles (BSF), and oil mist. RESULTS: After adjusting for smoking and age, we found that subjects with the highest cumulative exposure to fluoride (>0.16 mg/m(3) years) and inspirable dust (>2.9 mg/m(3) years) were two to four times more likely to report work-related wheeze and chest tightness than were unexposed subjects. Lower prevalence ratios for the same symptoms were seen with sulphur dioxide and BSF. Levels of lung function decreased slightly with exposure to oil mist, but not with cumulative exposure to other substances. CONCLUSIONS: This study suggests that the relevant causative agents for respiratory symptoms in aluminium smelters are fluoride and inspirable dust.     

Validation and reproducibility of computerised cell-viability analysis of tissue slices

Background

The identification of live cells using membrane integrity dyes has become a frequently used technique, especially with articular cartilage and chondrocytes in situ where tissue slices are used to assess cell recovery as a function of location. The development of a reproducible computerised method of cell evaluation would eliminate many variables associated with manual counting and significantly reduce the amount of time required to evaluate experimental results.

Methods

To validate a custom computerised counting program, intra-person and inter-person cell counts of nine human evaluators (three groups – unskilled, novice, and experienced) were compared with repeated pixel counts of the custom program on 15 digitised images (in triplicate) of chondrocytes in situ stained with fluorescent dyes.

Results

Results indicated increased reproducibility with increased experience within evaluators [Intraclass Correlation Coefficient (ICC) range = 0.67 (unskilled) to 0.99 (experienced)] and between evaluators [ICC = 0.47 (unskilled), 0.85 (novice), 0.93 (experienced)]. The computer program had perfect reproducibility (ICC = 1.0). There was a significant relationship between the average of the experienced evaluators results and the custom program results (ICC = 0.77).

Conclusions

This study demonstrated that increased experience in cell counting resulted in increased reproducibility both within and between human evaluators but confirmed that the computer program was the most reproducible. There was a good correlation between the intact cell recovery determined by the computer program and the experienced human evaluators. The results of this study showed that the computer counting program was a reproducible tool to evaluate intact cell recovery after use of membrane integrity dyes on chondrocytes in situ. This and the significant decrease in the time used to count the cells by the computer program advocate its use in future studies because it has significant advantages.

     

The reliability of ten-year dietary recall: implications for cancer research

Remote dietary intakes may be more important than recent diet in the etiology of cancer because of the long latency in cancer development. We examined the reliability of remote dietary recall over 10 y. Subjects were 56 adults participating in a cancer prevention trial in Western Australia. All subjects completed a 28-d diet record (DR) in 1991. A food-frequency questionnaire (FFQ) modified to ask respondents about their diet 10 y earlier was sent to each subject for completion in 2001. Remote intakes recalled from 10 y earlier using the FFQ were compared with the DR using the limits of agreement (LOA) method and Pearson correlation coefficients. Mean intakes of most nutrients did not differ between dietary methods. The LOA indicated that the FFQ could under- or overestimate DR estimates by >/=50%. For many nutrients, agreement between methods depended on the magnitude of intake. Pearson's correlation coefficients ranged from 0.02 for retinol to 0.66 for alcohol. These findings are similar to those of other studies that examined the reliability of recent and remote dietary intakes. They also show that using this FFQ, remote diet recalled from 10 y earlier may be as reliable as recent dietary recall.     

Preformulation experiences and in vitro model studies with spironolactone-containing suppositories

The optimal suppository base for the formulation of rectal suppositories containing diuretic spironolactone was selected experimentally. Model studies were carried out about the effect of solubility-increasing additives on the release of the drug from the suppositories. During the in vitro examinations acceptor phases of different pH values were used, and both diffusion time and the number of samplings were changed. Among the lipophilic and hydrophilic suppository bases studied the hydrophilic Macrogolum 1540 was found to be optimal. The release and diffusion of spironolactone was the most favourable from these suppositories. During storage these suppositories remained stable and the values of release did not decrease significantly (p < 0.05).     

Gibbs sampling-based segregation analysis of asthma-associated quantitative traits in a population-based sample of nuclear families

Asthma is a common, complex human disease. Elevated serum immunoglobulin E (IgE) levels, elevated blood eosinophil counts, and increased airway responsiveness are physiological traits that are characteristic of asthma. Few studies have investigated major gene effects for these traits in a population-based sample. Further, it is not known if any putative major genes may be common to two or more of these traits. We investigated the existence and nature of major genes modulating asthma-associated quantitative traits in an Australian population-based sample of 210 Caucasian nuclear families. The sharing of these major genes was also investigated. Segregation analysis was based upon a Markov Chain Monte Carlo (Gibbs sampling) approach as implemented in the program BUGS v0.6. All models included adjustment for age, height, tobacco smoke exposure, and gender. The segregation of total IgE levels, blood eosinophil counts, and dose-response slope (DRS) of methacholine challenge were all consistent with major loci at which a recessive allele acted to increase or decrease the phenotype. The respective estimated frequencies of the recessive alleles were 68% (total IgE), 10% (blood eosinophil count), and 27% (DRS). Extensive modelling suggested that the major loci controlling total serum IgE levels, blood eosinophil counts, and airway responsiveness represent different genes. These data provide evidence, for the first time, of the existence of at least 3 distinct genetic pathways involving major gene effects on physiological traits closely associated with asthma. These results have implications for gene discovery programs.     

Silent polymorphisms within the coding region of human sodium/hydrogen exchanger isoform-1 cDNA in peripheral blood mononuclear cells of leukemia patients: A comparison with healthy controls

We have examined the sequence of the cDNA encoding the sodium/hydrogen exchanger isoform 1 (NHE1), from 23 bases upstream of the start codon to 28 bases downstream of the stop codon. Template was prepared from (1) peripheral blood mononuclear cells (PBMC) isolated from 10 healthy unrelated Caucasian volunteers; (2) PBMCs isolated from 6 leukemic patients (acute lymphoblastic leukemia [ALL], n = 3; chronic lymphocytic leukemia [CLL], n = 1; chronic myelogenous leukemia [CML], n = 2); and (3) samples of 4 leukemic cell lines (ALL: CEM, MOLT4; AML: KG1a; CML: K562). NHE1 cDNA in normal PBMCs showed silent polymorphism of nucleotides 112 (N1: T, frequency 0.70; C, frequency 0.30; prevalence of heterozygosity 0.42); 2248 (N2: G, frequency 0.90; A, frequency 0. 10; heterozygosity 0.18); and 2493 (N3: G, frequency 0.90; A, frequency 0.10; heterozygosity 0.18). Deduced primary structure of NHE1 protein in all normal volunteers was identical to that previously published for NHE1 from renal and cardiac tissue. Similar to normal PBMCs, NHE1 cDNA from leukemic cells showed polymorphism of nucleotides N1, N2, and N3, but failed to demonstrate leukemia-specific sequence differences. We conclude that the coding region of NHE1 cDNA shows a greater level of polymorphism than is currently recognized, but that sequence mutation of NHE1 is not a key event in the pathogenesis of leukemia.