Evaluation of 41calcium as a new approach to assess changes in bone metabolism: effect of a bisphosphonate intervention in postmenopausal women with low bone mass

A new technique was evaluated to identify changes in bone metabolism directly at high sensitivity through isotopic labeling of bone Ca. Six women with low BMD were labeled with 41Ca up to 700 days and treated for 6 mo with risedronate. Effect of treatment on bone could be identified using 41Ca after 4-8 wk in each individual. INTRODUCTION: Isotopic labeling of bone using 41Ca, a long-living radiotracer, has been proposed as an alternative approach for measuring changes in bone metabolism to overcome current limitations of available techniques. After isotopic labeling of bone, changes in urinary 41Ca excretion reflect changes in bone Ca balance. The aim of this study was to validate this new technique against established measures. Changes in bone Ca balance were induced by giving a bisphosphonate. MATERIALS AND METHODS: Six postmenopausal women with diagnosed osteopenia/osteoporosis received a single oral dose of 100 nCi 41Ca for skeleton labeling. Urinary 41Ca/40Ca isotope ratios were monitored by accelerator mass spectrometry up to 700 days after the labeling process. Subjects received 35 mg risedronate per week for 6 mo. Effect of treatment was monitored using the 41Ca signal in urine and parallel measurements of BMD by DXA and biochemical markers of bone metabolism in urine and blood. RESULTS: Positive response to treatment was confirmed by BMD measurements, which increased for spine by +3.0% (p = 0.01) but not for hip. Bone formation markers decreased by -36% for bone alkaline phosphatase (BALP; p = 0.002) and -59% for procollagen type I propeptides (PINP; p = 0.001). Urinary deoxypyridinoline (DPD) and pyridinoline (PYD) were reduced by -21% (p = 0.019) and -23% (p = 0.009), respectively, whereas serum and urinary carboxy-terminal teleopeptides (CTXs) were reduced by -60% (p = 0.001) and -57.0% (p = 0.001), respectively. Changes in urinary 41Ca excretion paralleled findings for conventional techniques. The urinary 41Ca/40Ca isotope ratio was shifted by -47 +/- 10% by the intervention. Population pharmacokinetic analysis (NONMEM) of the 41Ca data using a linear three-compartment model showed that bisphosphonate treatment reduced Ca transfer rates between the slowly exchanging compartment (bone) and the intermediate fast exchanging compartment by 56% (95% CI: 45-58%). CONCLUSIONS: Isotopic labeling of bone using 41Ca can facilitate human trials in bone research by shortening of intervention periods, lowering subject numbers, and having easier conduct of cross-over studies compared with conventional techniques.

Hydrogel-based engineered skeletal muscle grafts normalize heart function early after myocardial infarction

Tissue engineering represents an attractive approach for the treatment of congestive heart failure. The influence of the differentiation of myogenic graft for functional recovery is not defined. We engineered a biodegradable skeletal muscle graft (ESMG) tissue and investigated its functional effect after implantation on the epicardium of an infarcted heart segment. ESMGs were synthesized by mixing collagen (2 mg/mL), Matrigel (2 mg/mL), and rat skeletal muscle cells (10(6)). Qualitative and quantitative aspects of ESMGs were optimized. Two weeks following coronary ligation, the animals were randomized in three groups: ESMG glued to the epicardial surface with fibrin (ESMG, n = 7), fibrin alone (fibrin, n = 5), or sham operation (sham, n = 4). Echocardiography, histology, and immunostaining were performed 4 weeks later. A cohesive three-dimensional tissular structure formed in vitro within 1 week. Myoblasts differentiated into randomly oriented myotubes. Four weeks postimplantation, ESMGs were vascularized and invaded by granulation tissue. Mean fractional shortening (FS) was, however, significantly increased in the ESMG group as compared with preimplantation values (42 +/- 6 vs. 33 +/- 5%, P < 0.05) and reached the values of controlled noninfarcted animals (control, n = 5; 45 +/- 3%; not significant). Pre- and postimplantation FS did not change over these 4 weeks in the sham group and the fibrin-treated animals. This study showed that it is possible to improve systolic heart function following myocardial infarction through implantation of differentiated muscle fibers seeded on a gel-type scaffold despite a low rate of survival.

Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes: experience of the PedPump Study in 17 countries

AIMS/HYPOTHESIS: To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome. METHODS: Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA(1c) was measured centrally. RESULTS: A total of 1,041 patients (age: 11.8 +/- 4.2 years; diabetes duration: 6.0 +/- 3.6 years; average CSII duration: 2.0 +/- 1.3 years; HbA(1c): 8.0 +/- 1.3% [means +/- SD]) participated. Glycaemic control was better in preschool (n = 142; 7.5 +/- 0.9%) and pre-adolescent (6-11 years, n = 321; 7.7 +/- 1.0%) children than in adolescent patients (12-18 years, n = 578; 8.3 +/- 1.4%). There was a significant negative correlation between HbA(1c) and daily bolus number, but not between HbA(1c) and total daily insulin dose. The use of <6.7 daily boluses was a significant predictor of an HbA(1c) level >7.5%. The incidence of severe hypoglycaemia and ketoacidosis was 6.63 and 6.26 events per 100 patient-years, respectively. CONCLUSIONS/INTERPRETATION: This large paediatric survey of CSII shows that glycaemic targets can be frequently achieved, particularly in young children, and the incidence of acute complications is low. Adequate substitution of basal and prandial insulin is associated with a better HbA(1c).

Combined magnetic resonance imaging and magnetic resonance spectroscopy imaging in the diagnosis of prostate cancer: a systematic review and meta-analysis

CONTEXT: Magnetic resonance imaging (MRI) combined with magnetic resonance spectroscopy imaging (MRSI) emerged as a promising test in the diagnosis of prostate cancer and showed encouraging results. OBJECTIVE: The aim of this systematic review is to meta-analyse the diagnostic accuracy of combined MRI/MRSI in prostate cancer and to explore risk profiles with highest benefit. EVIDENCE ACQUISITION: The authors searched the MEDLINE and EMBASE databases and the Cochrane Library, and the authors screened reference lists and contacted experts. There were no language restrictions. The last search was performed in August 2008. EVIDENCE SYNTHESIS: We identified 31 test-accuracy studies (1765 patients); 16 studies (17 populations) with a total of 581 patients were suitable for meta-analysis. Nine combined MRI/MRSI studies (10 populations) examining men with pathologically confirmed prostate cancer (297 patients; 1518 specimens) had a pooled sensitivity and specificity on prostate subpart level of 68% (95% CI, 56-78%) and 85% (95% CI, 78-90%), respectively. Compared with patients at high risk for clinically relevant cancer (six studies), sensitivity was lower in low-risk patients (four studies) (58% [46-69%] vs 74% [58-85%]; p>0.05) but higher for specificity (91% [86-94%] vs 78% [70-84%]; p<0.01). Seven studies examining patients with suspected prostate cancer at combined MRI/MRSI (284 patients) had an overall pooled sensitivity and specificity on patients level of 82% (59-94%) and 88% (80-95%). In the low-risk group (five studies) these values were 75% (39-93%) and 91% (77-97%), respectively. CONCLUSIONS: A limited number of small studies suggest that MRI combined with MRSI could be a rule-in test for low-risk patients. This finding needs further confirmation in larger studies and cost-effectiveness needs to be established.

Treatment of acute renal failure in the intensive care unit: lower costs by intermittent dialysis than continuous venovenous hemodiafiltration

Intermittent and continuous renal replacement therapies (RRTs) are available for the treatment of acute renal failure (ARF) in the intensive care unit (ICU). Although at present there are no adequately powered survival studies, available data suggest that both methods are equal with respect to patient outcome. Therefore, cost comparison between techniques is important for selecting the modality. Expenditures were prospectively assessed as a secondary end point during a controlled, randomized trial comparing intermittent hemodialysis (IHD) with continuous venovenous hemodiafiltration (CVVHDF). The outcome of the primary end points of this trial, that is, ICU and in-hospital mortality, has been previously published. One hundred twenty-five patients from a Swiss university hospital ICU were randomized either to CVVHDF or IHD. Out of these, 42 (CVVHDF) and 34 (IHD) were available for cost analysis. Patients' characteristics, delivered dialysis dose, duration of stay in the ICU or hospital, mortality rates, and recovery of renal function were not different between the two groups. Detailed 24-h time and material consumption protocols were available for 369 (CVVHDF) and 195 (IHD) treatment days. The mean daily duration of CVVHDF was 19.5 +/- 3.2 h/day, resulting in total expenditures of Euro 436 +/- 21 (21% for human resources and 79% for technical devices). For IHD (mean 3.0 +/- 0.4 h/treatment), the costs were lower (Euro 268 +/- 26), with a larger proportion for human resources (45%). Nursing time spent for CVVHDF was 113 +/- 50 min, and 198 +/- 63 min per IHD treatment. Total costs for RRT in ICU patients with ARF were lower when treated with IHD than with CVVHDF, and have to be taken into account for the selection of the method of RRT in ARF on the ICU.