Is dietary counselling effective in increasing dietary calcium,protein and energy intake in patients with osteoporotic fractures? A randomized controlled clinical trial

To determine the feasibility of increasing the calcium, protein and calorie intake of osteoporotic fracture patients by repeated dietary counselling delivered by a dietitian, a randomized controlled trial was conducted. Among 189 patients presenting with osteoporotic fractures to an Orthopaedics and Traumatology Department of a large regional hospital, 98 patients were randomized to the intervention group and 91 were randomized to the control group (with usual care). Intervention group received three sessions of dietary counselling with tailored made recommendations over a period of 4 months, while the control group only received dietary assessment and pamphlets on the prevention of osteoporosis. Almost all subjects in both intervention and control groups had calcium intake below the recommended level of 1000 mg at baseline. Half and 60% of subjects in both groups had total energy and protein intake below recommended levels respectively. The mean weights of control and intervention groups at baseline were 51.5 and 50.9 kg respectively, while the body mass index (BMI) were 22.6 (kg m(-2)) and 22.6 (kg m(-2)) respectively. After dietary intervention, significant increase of intake was seen in calcium intake (P = 0.0095 by t-test) in the intervention group. No significant increase was seen in protein or calorie intake. No significant change was observed in the body weight or BMI although there was a positive trend in the intervention group for all these parameters. We concluded that there was general malnutrition in Chinese elderly who presented with osteoporotic fractures. Dietary calcium could be increased by repeated professional dietary counselling. Future studies with longer duration and more objective clinical outcomes will be helpful to further demonstrate the long-term effects of dietary intervention on osteoporosis and other chronic diseases.     

Prognostic relevance of histological grade and its components in node-negative breast cancer patients.

Available results highlight the lack of good level of evidence studies on the pure prognostic value of histological grade. In the present study, the prognostic relevance of histological grade and of its three components, tubule formation, nuclear pleomorphism and mitotic count, was analyzed in a series of 372 patients with node-negative breast cancer treated with locoregional therapy alone until early relapse. Histological grade was determined blindly by two observers and discordance between evaluations was resolved after joint review using a multihead microscope. No relation was observed between histological grade and any of its three components and disease-free survival. Conversely, a significant relation was observed between histological grade and distant metastasis-free survival (at 6 years, 94, 86 and 76% for grades 1, 2 and 3, respectively, P=0.013) as well as overall survival (98, 90 and 86%, P=0.001). A breakdown analysis as a function of the three components showed that neither tubule formation nor nuclear pleomorphism was associated with prognosis, and only mitotic count strongly influenced both distant metastasis-free survival (91, 82 and 74%, P=0.014) and overall survival (97, 87 and 85%, P=0.011). Histological grade suffers from a much higher subjectivity than any other microscopic evaluation of biomarkers as it is the sum of three different morphological features. Within the Italian Network for Quality Assessment of Tumor Biomarkers program we observed that histological grade is an independent prognostic variable, but also that this role is ascribable only to the number of mitotic figures. In conclusion, due to the ever smaller size of diagnosed breast cancers, resulting in less cancer tissue for biofunctional and molecular analysis, mitotic count evaluated under strict quality control conditions seems to be an accurate and feasible prognostic variable.     

A REPRODUCIBLE MODEL OF CHRONIC REJECTION IN RAT RENAL ALLOGRAFTS

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 668 after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.     

Long-term effects of physiologic concentrations of dexamethasone on human bone-derived cells

Bone cells derived from human trabecular explants display osteoblastic features. We examined the modulation of alkaline phosphatase activity and cAMP production as the result of exposing trabecular explants to physiologic concentrations of dexamethasone for 4 weeks during cellular outgrowth and subculture. Cells treated with dexamethasone were observed to grow generally more slowly than control cells. Cells appeared larger and more polygonal, and staining for alkaline phosphatase was more intense in the dexamethasone-exposed cultures. There was a progressive increase in cellular PTH responsiveness with increasing duration of exposure of cells to dexamethasone. Cells grown for 6 weeks in 3 x 10(-8) M dexamethasone had a 10-fold increase in PTH-stimulated cyclic AMP accumulation. Dexamethasone-treated cells also had a significantly increased alkaline phosphatase activity. 1,25-(OH)2D3-stimulated alkaline phosphatase activity was increased approximately 20-fold. cAMP responses were significantly increased to PTH (21.7-fold), PGE1 (2.67-fold), and forskolin (4.81-fold), but not to cholera toxin. Dexamethasone-treated cells also had a mean decrease in 1,25-(OH)2D3-stimulated osteocalcin production to 26.2% of control values (p less than 0.001). Hydrocortisone treatment gave rise to similar effects but of smaller magnitude than those of dexamethasone. Testosterone did not have a significant effect on alkaline phosphatase activity or cAMP production. Skin fibroblasts showed a significant enhancement of alkaline phosphatase activity in response to dexamethasone, but of a much smaller magnitude than in bone cells. The phenotypic changes induced by long-term culture in dexamethasone are consistent with the promotion of a more differentiated osteoblastic phenotype.     

Desferrithiocin is an effective iron chelator in vivo and in vitro but ferrithiocin is toxic

The efficacy and toxicity of the siderophore desferrithiocin (DFT), which has shown potential application in iron chelation therapy, were assessed in vivo and in vitro. DFT was evaluated in vivo in two ways: firstly, by measuring the effect of a single dose of DFT (10-100 mg/kg) on 59Fe excretion in iron-loaded rats labelled with 59Fe; and secondly, by examining the effect of the daily oral administration for 2 weeks of DFT (10-25 mg/kg/d) on the growing rat. DFT and its ferric complex, ferrithiocin (FT), were assessed in vitro from their effects on transferrin and iron uptake and mobilization from rat hepatocytes in culture using transferrin doubly labelled with 125I and 59Fe. Both oral and subcutaneous DFT were highly effective in promoting iron excretion in vivo, but showed evidence of toxicity after oral administration for 2 weeks at 25 mg/kg/d. In addition, DFT was much more effective than desferrioxamine or pyridoxal isonicotinyl hydrazone in reducing hepatocyte iron in vitro. However, FT was cytotoxic, causing membrane disruption and release of intracellular aspartate aminotransferase. It was concluded that DFT should not be considered for chronic iron chelation therapy without extensive further evaluation.     

Electrophysiological properties of neurons in the rostral ventrolateral medulla of normotensive and spontaneously hypertensive rats

Single unit activities were recorded from the rostral ventrolateral medulla (RVL) of pentobarbital-anesthetized normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Throughout the recording period, arterial blood pressures of WKY (mean arterial pressure, MAP = 103.1 mm Hg) and SHR (MAP = 159.2 mm Hg) remained stable at the respective basal levels. The units recorded in this study were all spontaneously active and cardiac-locked. Two types of discharge patterns, namely single and double discharges, were identified. These single and double discharge units were found to distribute randomly in RVL. In WKY, 92.6% of RVL neurons exhibited single discharges whereas in SHR, the majority (57%) of RVL neurons exhibited double discharges. The mean firing rate of single discharge units in RVL of SHR was significantly higher than that of WKY, whereas the mean firing rate of double discharge units in WKY was similar to that of SHR. About half of the units studied were also tested for antidromic collision; all units tested could be antidromically activated from the intermediolateral column (IML) of the thoracic spinal cord and the lowest threshold sites were consistently localized within IML. In both groups of rats, the axonal conduction velocity of RVL neurons showed a bimodal distribution viz. the fast and slow conducting axons. The mean conduction velocities of each of these two groups of neurons in WKY and SHR were similar. Most of the double discharge units in WKY and SHR belonged to the fast conducting type.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of aerobic conditioning and/or caloric restriction in overweight men and women

The purpose of this study was to compare the effects of exercise and/or caloric restriction for 12 wk on body composition, maximal aerobic power (VO2max), and serum lipids and lipoproteins in overweight individuals. Forty-eight males and 48 females (means age = 36.6 yr), 120-140% of ideal body weight, were randomly assigned to groups (N = 12 each) of diet-exercise (DE), diet (D), exercise (E), and sedentary control (C). The dietary regimen consisted of 1,200 kcal X d-1, while exercise consisted of 5 d X wk-1 of 30 min of walk/running. For the males, body weight (BW) and fat weight loss in the DE group (-11.8 and 23%, respectively) were significantly greater than in the D group (-9.1 and -18%), with both groups significantly greater than for E and C. In the females, BW and fat weight loss for DE (-10.4 and -24%) were significantly greater than for D (-7.8 and -20%), with both groups significantly greater than E and C. Both DE and D males and females had a decrease in fat-free weight of -4.5 and -2.4%, respectively. In both sexes, the increase in VO2max-BW (ml X kg -1 X min-1) in DE (25%) was significantly greater than for E (15%), D (11%), and C (0%), with differences between E and D nonsignificant. However, increases in absolute VO2max (1 X min-1) and VO2max-fat-free weight (ml X kg-1 X min-1) were similar (P greater than 0.05) for DE and E (14%) but significantly greater compared to D and C (2%).(ABSTRACT TRUNCATED AT 250 WORDS)