W. D. Evans

Measured and predicted bone mineral content in healthy boys and girls aged 6-18 years: adjustment for body size and puberty

Dual‐energy X‐ray absorptiometry (DEXA) is a rapid and precise technique for the assessment of bone mineralization in children. Interpretation of the results in growing children is complex as results are influenced by age, body size (height and weight) and puberty. Conventionally, bone mineral data derived from DEXA have been presented as an areal density [BMD; bone mineral content (BMC, g)/projected bone area (BA, cm2)], yet this fails to account for changes in BMC that result from changes in age, body size or pubertal development. Measurement of BMC and BA of the whole body, lumbar spine and left hip were made in 58 healthy boys and girls using DEXA. The relationship between BMC and BA was curvilinear, with the best fit being that of a power model (BMD = BMC/BAλ, where λ is the exponent to which BA is raised in order to remove its influence on BMC). The value of λ changed when measures of body size and puberty were taken into account (e.g. for lumbar spine from 1.66 to 1.49). Predictive formulae for BMC were produced using regression analysis and based on the variables of age, body size and pubertal development. This provides a method for interpreting the measured BMC which is independent of such variables and a constant reference range for children aged 6–18 y.

Inflammatory bowel disease and predisposition to osteopenia

The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energyx ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p<0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids.

Relative osteopenia after treatment for acute lymphoblastic leukemia.

Osteoporosis in adult life is associated with a significant morbidity and may be predisposed to by osteopenia and failure to reach peak bone mass in childhood. Children treated for acute lymphoblastic leukemia (ALL) may be at risk of osteopenia as a result of previous therapy or as a consequence of the disease process itself. Dual energy x-ray absorptiometry measurements of bone mineral content (BMC) for the whole body and at the lumbar spine and hip were taken in 35 (14 male) long-term survivors of ALL and compared with results in 20 (10 male) survivors of other malignancies and 31 (17 male) healthy sibling controls. The measured BMC was expressed as a percentage of a predicted value derived from the control group and based on the variables that had influence upon it. BMC (%) was reduced at the spine in the ALL group compared with controls [92.4 (8.0)% versus 100.4 (9.7)%, respectively; p < 0.005] and at the hip compared with both other malignancies and controls [89.0 (11.5)% versus 96.1 (11.7)% and 100.4 (9.2)%, respectively; p < 0.0005]. Increasing length of time off therapy was associated with a significant increase in %BMC at both the spine and the hip. For the spine, this association was significantly different between the ALL group and other malignancies, suggesting that any gain in %BMC after therapy was slower in children treated for ALL. Both exercise capacity and levels of physical activity were correlated with %BMC at the hip (r = 0.44, p < 0.001 and r = 0.29, p < 0.01, respectively). Previous exposure to methotrexate, ifosfamide, and bleomycin was associated with a reduction in %BMC at the spine. Exposure to 6-mercaptopurine and cisplatin was associated with a reduction at the hip. In conclusion, children treated for ALL are osteopenic. The mechanism is probably multifactorial but is partially related to previous chemotherapy, limited exercise capacity, and relative physical inactivity.

The spectrum of relativistic one-electron atoms according to Bethe and Salpeter

Bethe and Salpeter introduced a relativistic equation — different from the Bethe-Salpeter equation — which describes relativistic multi-particle systems. Here we will begin some basic work concerning its mathematical structure. In particular we show self-adjointness of the one-particle operator which will be a consequence of a sharp Sobolev type inequality yielding semi-boundedness of the corresponding sesquilinear form. Moreover we locate the essential spectrum of the operator and show the absence of singular continuous spectrum.

Circulating matrix metalloproteinase-9 and osteoporosis in patients with chronic obstructive pulmonary disease:

Matrix metalloproteinase-9 (MMP-9) has been implicated in airways injury in chronic obstructive pulmonary disease (COPD). Osteoporosis is common in patients with COPD, and MMP-9 is an indicator of activated osteoclasts. We hypothesized that circulating MMP-9 would be related to bone mineral density (BMD) in COPD. We explored the relationship between MMP-9, tissue inhibitors of metalloproteinases (TIMP)-1 and -2, and BMD status in patients with COPD. A total of 70 clinically stable patients with confirmed COPD and 39 control subjects underwent spirometry, dual-energy x-ray absorptiometry to determine BMD, and venous sampling for measurement of cytokines and MMP-9 and TIMP-1 and -2. In patients, circulating MMP-9 was increased: mean (SD) 38.5 (2.2) compared with control subjects 20.1 (2.0) ng/mL, P < 0.001, whereas TIMP-1 and -2 were not different. In the patients, MMP-9 was greater in those with osteoporosis, compared with those with osteopenia, no bone disease or control subjects, and patients with osteopenia had greater MMP-9 than control subjects. The adjusted receiver operating characteristics curve area for MMP-9 detecting osteoporosis was 0.86. Patients had elevated systemic inflammatory mediators compared with control subjects, but these were unrelated to bone status. Increased circulating MMP-9 in patients with COPD was related to the presence of osteoporosis and not to lung function. MMP-9 may be a biomarker of increased bone resorption.

Osteopenia, excess adiposity and hyperleptinaemia during 2 years of treatment for childhood acute lymphoblastic leukaemia without cranial irradiation

objective  Osteopenia and excess adiposity occur following treatment of childhood acute lymphoblastic leukaemia (ALL) and the use of cranial irradiation is thought to be a significant contributory factor. Hyperleptinaemia has also been demonstrated following cessation of treatment for childhood ALL. Therefore a prospective study was undertaken to evaluate serial changes in percentage bone mineral content (BMC), adiposity and serum leptin concentrations during 2 years of treatment of children with ALL with chemotherapy but without cranial irradiation.

Effect of replacement doses of thyroxine on bone mineral density

Hyperthyroidism is associated with a reduction in bone mineral density (BMD). Suppressive doses of thyroxine (T4), inducing subclinical hyperthyroidism, have been reported by some investigators to reduce BMD. Little work has been done on replacement doses of T4.

ON THE SPECTRUM OF SECOND-ORDER DIFFERENTIAL OPERATORS WITH COMPLEX COEFFICIENTS

The main objective of this paper is to extend the pioneering work of Sims on second-order linear differential equations with a complex coefficient, in which he obtains an analogue of the Titchmarsh–Weyl theory and classification. The generalization considered exposes interesting features not visible in the special case in Sims paper from 1957. An m-function is constructed (which is either unique or a point on a ‘limit-circle’), and the relationship between its properties and the spectrum of underlying m-accretive differential operators analysed. The paper is a contribution to the study of non–self–adjoint operators; in general, the spectral theory of such operators is rather fragmentary, and further study is being driven by important physical applications, to hydrodynamics, electro–magnetic theory and nuclear physics, for instance.

ON THE EVALUATION OF THE NORM OF AN INTEGRAL OPERATOR ASSOCIATED WITH THE STABILITY OF ONE-ELECTRON ATOMS

The norm of an integral operator occurring in the partial wave decomposition of an operator B introduced by Brown and Ravenhall in a model for relativistic one-electron atoms is determined. The result implies that B is non-negative and has no eigenvalue at 0 when the nuclear charge does not exceed a specified critical value.

Spectral Analysis of Relativistic Operators

Over the last decade, there has been considerable interest and progress in determining the spectral properties of various operators that take relativistic effects into account, with important implications for mathematics and physics. Difficulties are encountered in many-particle problems due to the lack of semiboundedness of the Dirac operator, and this has led to the investigation of operators like those of Chandrasekhar–Herbst and Brown–Ravenhall, which are semibounded under appropriate circumstances. This book contains an up-to-date, comprehensive and self-contained analysis of the spectral properties of these operators, providing the tools for anyone working in this area. Another major feature is the work of the authors on zero modes, a topic which has important significance for the stability of matter and other physical problems. Up until now, these topics have been scattered throughout the literature, without a systematic and cohesive treatment. The book will report largely on the progress on these topics published since 1992.