Noonan's and DiGeorge syndromes with monosomy 22q11

A boy with the dysmorphic features of Noonan's syndrome and pulmonary valve stenosis who had evidence of hypoparathyroidism and abnormal T lymphocyte numbers in the neonatal period is reported. He had a normal karyotype but molecular analysis revealed a submicroscopic deletion within chromosome 22q11, the region deleted in DiGeorge syndrome. Thus this child has both Noonan's syndrome and DiGeorge syndrome; 22q11 is a candidate region for a gene defective in Noonan's syndrome.     

Serum total cholesterol and ferritin and blood haemoglobin concentrations in primary schoolchildren

Serum total cholesterol and ferritin and haemoglobin concentrations were measured in blood samples obtained by venepuncture in 378 of 593 children aged 5-6 or 8-9 years from seven primary schools in Canterbury. This study formed part of an investigation to assess the feasibility of including a venepuncture procedure for monitoring purposes in primary schoolchildren. Although only one child had a very low haemoglobin concentration of 61 g/l, a large percentage, 25% in the rising 6 years and 7% in the rising 9 years, had concentrations between 100 and 115 g/l--that is, less than the reference fifth centile. Eight per cent had a serum ferritin concentration less than 8 micrograms/l. Cholesterol concentrations higher than 5.2 mmol/l were found in 20% of the 5-6 year olds and 23% of the 8-9 year olds, and in 19% of boys and 25% of girls. About 5% of children had cholesterol concentrations above 6 mmol/l. The number of children with anaemia, iron deficiency, and high cholesterol raises serious concerns about the nutritional and coronary heart disease risk of British children.     

Longitudinal effects of change in body mass on measurements of ventilatory capacity.

BACKGROUND: In several longitudinal studies changes in body mass and in forced expiratory volume in one second (FEV1) have been found to be negatively correlated. This paper tests the hypothesis that failure to allow for the association can lead to error in the interpretation of longitudinal measurements of ventilatory capacity. METHODS: Male shipyard workers (n = 1005) were assessed on two occasions with an average interval between measurements of 6.9 years. A respiratory symptoms questionnaire, detailed anthropometric measurements, and dynamic spirometric tests were undertaken. Multiple regression analysis was used to identify variables which contributed to the changes in lung function. RESULTS: After allowing for age and growth in stature, a change in body mass of 1 kg was, on average, associated with a mean (SE) converse change in FEV1 of 17.6 (2.0) ml, and in forced vital capacity (FVC) of 21.1 (2.5) ml. Neglect of changes in body mass (which in this context reflected changes in body fat) led to underestimation of the longitudinal decline in FEV1 with age and failure to detect significant improvements in FEV1, both in smokers following discontinuation of smoking and in shipyard welders and caulker/burners as a consequence of leaving their employment. The estimated peak ages and associated peak levels of the indices were found to differ, depending on whether or not they were expressed at constant body mass. CONCLUSIONS: Neglect of changes in body mass can lead to erroneous conclusions being drawn from longitudinal measurements of FEV1.     

Reproducibility of non-specific bronchial challenge in adults: implications for design, analysis and interpretation of clinical and epidemiological studies

BACKGROUND: Poor reproducibility of an outcome measure reduces power and, in an independent variable, biases results. The intraclass correlation coefficient measures loss of power and degree of bias. Information is lacking on the intraclass correlation coefficient for bronchial responsiveness and factors affecting reproducibility. METHODS: Papers containing information on reproducibility of bronchial responsiveness were identified using a Medline search and citations. Within and between person components of variance of PD20 or PC20 were expressed in doubling dose or concentration units, and the intraclass correlation coefficient calculated when not reported. RESULTS: Results were extracted from 32 papers. Intraclass correlation coefficients were over 0.9 in short term studies of highly selected asthmatic patients, but larger and most long term studies had lower intraclass correlation coefficients, less than 0.5 in some cases, due to greater within person or lower between person variation. Reproducibility of dose or concentration-response slope was generally higher, but still less than that of forced expiratory volume in 1 second. CONCLUSIONS: Information is available to calculate sample size for studies with bronchial responsiveness as the outcome, but results when bronchial responsiveness is an explanatory variable may be misleading.     

A list of device-specific thresholds for the clinical interpretation of peripheral x-ray absorptiometry examinations

The UK National Osteoporosis Society (NOS) has recently issued new guidelines on the use of peripheral x-ray absorptiometry (pDXA) devices in managing osteoporosis. The NOS guidelines recommend a triage approach in which patients bone mineral density (BMD) measurements are interpreted using upper and lower thresholds specific to each type of pDXA device. The thresholds are defined so that patients with osteoporosis at the hip or spine are identified with 90% sensitivity and 90% specificity. Patients with a pDXA result below the lower threshold are likely to have osteoporosis at the hip or spine, patients with a result above the upper threshold are unlikely to have osteoporosis, while those between the two thresholds require a hip and spine BMD examination for a definitive diagnosis. This report presents data from a multicenter study to establish the triage thresholds for a range of pDXA devices in use in the UK. The subjects were white female patients aged 55–70 years who met the normal referral criteria for a BMD examination. For each device, at least 70 women with osteoporosis at the hip or spine and 70 women without osteoporosis were enrolled. All women had hip and spine BMD measurements using axial DXA systems that were interpreted using the National Health and Nutrition Examination Survey (NHANES) reference range for the hip and the manufacturers reference ranges for the spine. Data are presented for five different devices: the Osteometer DTX-200 (forearm BMD), the Schick AccuDEXA (hand BMD), the GE Lunar PIXI (heel BMD), the Alara MetriScan (hand BMD), and the Demetech Calscan (heel BMD). The clinical measurements were supplemented by theoretical modeling to estimate the age dependence of the triage thresholds and the effect of the correlation coefficient between pDXA and axial BMD on the percentage of women referred for an axial BMD examination. In summary, this study provides thresholds for implementing the new NOS guidelines for managing osteoporosis using pDXA devices. The figures reported apply to postmenopausal white women aged 55–70 years who meet the conventional criteria for a BMD examination. The results confirm that the thresholds are specific to each type of pDXA device and that the NOS triage algorithm requires 40% of women to have an axial DXA examination.On behalf of the National Osteoporosis Society Bone Densitometry Forum.