Effective treatment of malignant hypercalcaemia with a single intravenous infusion of clodronate.

Thirty patients with hypercalcaemia due to malignancy that persisted following rehydration, were treated with a single dose of the bisphosphonate, clodronate. Clodronate (1.5 g) was administered intravenously in 500 ml normal saline over 4 h. Serum and urine biochemistry were measured before and after treatment and the results were compared with data from 15 patients given the recommended regimen 300 mg intravenous clodronate daily for 5 consecutive days. The single infusion induced a rapid and significant fall in serum calcium, apparent at day 3 (P < 0.0001) that persisted to the end of follow-up at day 10 (P < 0.001). Eighty per cent (24/30) of patients became normocalcaemic. The response was associated with a significant decrease in fasting urinary calcium excretion, and no change in renal function, as judged by serum creatinine. The same dose of clodronate, given as 5 daily infusions, induced a comparable decrease in serum calcium, but was less rapid in onset so that at day 3 the serum calcium was significantly lower with the single infusion (P = 0.02). The calcium lowering effect of both regimens depended on the tumour type. We conclude that the single infusion of 1500 mg clodronate is as effective in reducing serum calcium as the same dose given over 5 days. The single infusion has a more rapid onset of effect, is more convenient than multiple infusions, and has no adverse effect on renal function

Contributions of clinical and technical factors to longitudinal change in trabecular bone score and bone density: a registry‐based individual‐level analysis

Lumbar spine trabecular bone score (TBS), a grey-level texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. An unresolved question is whether TBS is sufficiently responsive to change over time or in response to widely used osteoporosis therapy at the individual level to serve as a useful biomarker. Using the Manitoba DXA Registry we identified 11,643 individuals age 40 years and older with two fan-beam DXA scans performed on the same instrument within 5 years (mean interval 3.2 years), of whom 6,985 (60.0%) received antiresorptive osteoporosis medication (majority oral bisphosphonate) between the scans. We examined factors that were associated with a change in lumbar spine TBS, lumbar spine BMD and total hip BMD exceeding the 95% least significant change (LSC). Change exceeding the LSC was identified in 23.0% (9.3% increase, 13.8% decrease) of lumbar spine TBS, 38.2% (22.1% increase, 16.1% decrease) lumbar spine BMD, and 42.5% (17.6% increase, 24.9% decrease) total hip BMD measurement-pairs. From regression models, the variables most strongly associated with significant change in TBS (decreasing order) were tissue thickness change, acquisition mode change, weight change and spine percent fat change. Consistent with the insensitivity of TBS to oral antiresorptive therapies, use of these agents showed very little effect on TBS change. In contrast, for both spine BMD change and total hip BMD change, osteoporosis medication use was the most significant variable, while tissue thickness change, acquisition mode change and weight change had relatively weak effects. In summary, change in spine TBS using the present algorithm appears to be strongly affected by technical factors. This suggests a limited role, if any, for using TBS change in untreated individuals or for monitoring response to anti-resorptive treatment in routine clinical practice with the current version of the TBS algorithm

Fingerprinting the impacts of global change on tropical forests

Recent observations of widespread changes in mature tropical forests such as increasing tree growth, recruitment and mortality rates and increasing above-ground biomass suggest that 'global change' agents may be causing predictable changes in tropical forests. However, consensus over both the robustness of these changes and the environmental drivers that may be causing them is yet to emerge. This paper focuses on the second part of this debate. We review (i) the evidence that the physical, chemical and biological environment that tropical trees grow in has been altered over recent decades across large areas of the tropics, and (ii) the theoretical, experimental and observational evidence regarding the most likely effects of each of these changes on tropical forests. Ten potential widespread drivers of environmental change were identified: temperature, precipitation, solar radiation, climatic extremes (including El Niño Southern Oscillation events), atmospheric CO2 concentrations, nutrient deposition, O3/acid depositions, hunting, land-use change and increasing liana numbers. We note that each of these environmental changes is expected to leave a unique 'fingerprint' in tropical forests, as drivers directly force different processes, have different distributions in space and time and may affect some forests more than others (e.g. depending on soil fertility). Thus, in the third part of the paper we present testable a priori predictions of forest responses to assist ecologists in attributing particular changes in forests to particular causes across multiple datasets. Finally, we discuss how these drivers may change in the future and the possible consequences for tropical forests

Effects of classification context on categorization in natural categories

The patterns of classification of borderline instances of eight common taxonomic categories were examined under three different instructional conditions to test two predictions: first, that lack of a specified context contributes to vagueness in categorization, and second, that altering the purpose of classification can lead to greater or lesser dependence on similarity in classification. The instructional conditions contrasted purely pragmatic with more technical/quasi-legal contexts as purposes for classification, and these were compared with a no-context control. The measures of category vagueness were between-subjects disagreement and within-subjects consistency, and the measures of similarity based categorization were category breadth and the correlation of instance categorization probability with mean rated typicality, independently measured in a neutral context. Contrary to predictions, none of the measures of vagueness, reliability, category breadth, or correlation with typicality were generally affected by the instructional setting as a function of pragmatic versus technical purposes. Only one subcondition, in which a situational context was implied in addition to a purposive context, produced a significant change in categorization. Further experiments demonstrated that the effect of context was not increased when participants talked their way through the task, and that a technical context did not elicit more all-or-none categorization than did a pragmatic context. These findings place an important boundary condition on the effects of instructional context on conceptual categorization