Validation of the sheep as a large animal model for the study of vertebral osteoporosis.

Rats have long been the animal of choice for research in the field of osteoporosis. In the search for a complementary large animal model the sheep appears useful but hitherto the extent of bone loss from the spine has failed to reach a level that is generally accepted as osteoporotic in humans. Osteoporosis was induced in ten sheep using ovariectomy, low calcium diet and steroid injection for 6 months. Bone samples of iliac crest (IC), lumbar spine (LS), and proximal femur (PF) from the osteoporotic sheep were compared with those from four normal sheep using densitometry, histomorphometry, biochemistry and basic mechanical testing. The differences were examined using an analysis of variance with Tukey-Kramer test. Overall, the bone mineral density at LS and PF decreased more than 25% after treatment. Trabecular bone volume decreased by 29.2, 33.4 and 42.6% in IC, LS and PF, respectively. The failure load of the LS in axial compression was reduced to 2,003 from 6,140 N. The extent of bone loss was sufficient to categorise these sheep as osteoporotic although the pattern of bone loss varied between sites. Reduced mechanical competence in LS confirmed the suitability of this model for evaluation of potential treatments for osteoporosis.

Health and well-being of farm women: contradictory roles in the contemporary economy.

To document the roles of farm women in the contemporary farm economy, their physical health and psychological well-being, and their interaction with and evaluation of the health care system, a multi-stage study employing both quantitative and qualitative research strategies was implemented. A total of 717 Canadian farm women in 20 rural Saskatchewan municipalities returned a 20-page objective questionnaire that focused on: (1) health care, (2) health status, (3) social support, (4) well-being, (5) lifestyle and activities, (6) stress, (7) work, (8) male and female roles, (9) demographics, and (10) farm issues. Subsequently, 20 qualitative interviews were conducted to explore in-depth the findings of the survey. Results document long hours of work, on and off the farm, that often went unacknowledged; pressure to assume the role of a "traditional farm wife," expectations they often felt they had difficulty living up to; and high levels of stress in response to economic and family pressures. Although rating the availability and quality of health care as "fair to good," the farm women commented on the lack of access to medical and counseling services, and a perceived lack of understanding by policymakers and professionals. Integrated health and educational service centers, increased use of nurse practitioners, and establishment of mobile health services are recommended policy initiatives.

Antenatal determination of fetal brain activity in response to an acoustic stimulus using functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) is now a well-established technique for directly identifying adult brain activity. This study builds on earlier pilot work that showed that fMRI could provide direct evidence of fetal brain cortical activation in response to an auditory stimulus. The new work presented here aims to assess the sensitivity of this technique in a larger sample group. This article includes a specific discussion of the methodology required for fetal fMRI. Sixteen pregnant subjects were scanned between 37 and 41 weeks gestation, 12 had an auditory stimulus applied to the maternal abdomen (study group) and 4 had an auditory stimulus applied to the mother's ears (control group). Two of twelve (2/12) study-group patients experienced back pain so that the experiment was abandoned; 4/12 showed significant activation (P < 0.005) in one or both of the temporal lobes; 1/12 showed significant activation in the frontal lobe. A susceptibility artifact at the interface between the maternal bowel and the fetus affected 3/12 data sets. No significant activation was found in 3/4 of the control cases, and 1/4 could not be analyzed due to a susceptibility artifact.

Renal and haemodynamic effects of amlodipine and nifedipine in hypertensive renal transplant recipients.

BACKGROUND: Immunosuppressive treatment with cyclosporin A (CsA) improves the survival of renal allografts, but is associated with renal vasoconstriction and hypertension. Previous reports suggest that the calcium-channel blockers nifedipine and amlodipine may improve graft function in CsA-treated patients. We have compared the effects of amlodipine (5-10 mg once daily) and nifedipine retard (10-40 mg twice daily) on renal function and blood pressure in renal transplant recipients treated with CsA. METHODS: This was a multicentre, two-way, crossover study in 27 evaluable hypertensive patients with renal insufficiency following renal transplantation, who were maintained on a stable dose of CsA. Patients received either amlodipine (5-10 mg once daily) or nifedipine retard (10-40 mg twice daily) for 8 weeks, and were then crossed over to the other treatment for a further 8 weeks. RESULTS: Trends were seen during amlodipine treatment towards larger improvements, in serum creatinine (by 8% of baseline on amlodipine vs 4% on nifedipine), lithium clearance (13% vs 2%), and glomerular filtration rate 11% vs 7%). Effective renal plasma flow was increased by 11% of baseline on nifedipine vs 9% on amlodipine. There were no significant differences between treatments. Amlodipine and nifedipine lowered systolic blood pressure to a similar extent (21 mmHg vs 15 mmHg respectively, P=0.25), but amlodipine was more effective than nifedipine in lowering diastolic blood pressure (13 mmHg vs 8 mmHg, P=0.006). Both treatments were well tolerated. CONCLUSION: Once-daily amlodipine is at least as effective as twice-daily nifedipine retard in controlling blood pressure and does not adversely affect graft function in hypertensive renal allograft recipients.

Estradiol treatment transiently increases trabecular bone volume in ovariectomized rats.

The effect of short-term estradiol treatment, administered from the time of ovariectomy, on increased bone turnover and subsequent bone loss was studied in the rat. Adult female Sprague-Dawley rats were ovariectomized and administered daily subcutaneous (s.c.) injections of 17 beta-estradiol at 8 micrograms/ kg per day (Low) and 20 micrograms/kg per day (High) or vehicle alone (Veh). Femoral trabecular bone volume (BV/TV) and trabecular number (Tb.N) in the distal femur were transiently increased at 6 days postoperation in a dose-dependent manner following estradiol administration [mean +/- SEM: BV/TV (%), day 0, 6.6 +/- 0.2; day 6, Veh 7.8 +/- 0.4, Low 10.2 +/- 2.2, High 12.8 +/- 1.7 (p < 0.05); Tb.N (/mm), day 0, 2.30 +/- 0.24; day 6, Veh 2.89 +/- 0.33, Low 3.4 +/- 0.7, High 4.39 +/- 0.34 (p < 0.05)]. Estradiol prevented the ovariectomy-induced decrease in BV/TV and Tb.N between 9 and 15 days observed in Veh rats. Both serum alkaline phosphatase and urine hydroxyproline excretion were maintained at preoperative levels or lower from day 6 postoperation with high dose estradiol. Serum osteocalcin, however, rose above preoperative levels with estradiol at days 6 and 9, but returned to these values on days 15 and 21 postoperation. These results suggest that estradiol, administered from the time of ovariectomy, immediately suppressed markers associated with osteoblast proliferation/matrix synthesis and bone resorption. Mineralization does not appear to be so rapidly suppressed by estradiol with relatively high levels immediately following administration, resulting in a transient increase in trabecular bone volume and trabecular number.

Acute renal failure and fluid retention and kidney damage in copper-deficient rats fed a high-NaCl diet.

The effect of an interaction between Cu status and dietary NaCl level on kidney structure, water balance, and the plasma renin-angiotensin-aldosterone system (RAAS) was examined in 64 male Sprague-Dawley rats (178 gm) fed a copper-supplemented diet (CuS) (10 micrograms Cu per gram) or a copper-deficient diet (CuD) (less than 0.7 micrograms Cu per gram), with (CuSNa, CuDNa) or without 3% NaCl for 42 days. NaCl did not affect growth, fluid retention, or kidney ultrastructure in Cu-supplemented rats. Cu deficiency decreased growth rate and kidney Cu, increased plasma cholesterol concentration, and suppressed plasma RAAS. NaCl increased the magnitude of these changes in Cu-deficient rats. The mortality rate was higher in CuDNa (8/16) than in Cu-deficient (2/16) rats. An acute renal failure syndrome characterized by tissue edema, pleural effusion, and ascites occurred in rats fed CuDNa. Bioelectric impedence analysis indicated that body water content was similar in rats fed CuS, CuSNa, and CuD but was higher in edematous and nonedematous rats fed CuDNa. Transmission electron microscopy indicated that glomeruli from Cu-deficient rats were poorly perfused and often occluded by expanded mesangium and contained numerous lysozome-like bodies. Fusion of podocyte foot processes, derangement of glomerular basement membrane, and hypertrophy and lipid accumulation by glomerular capillary endothelium were present in tissue from rats fed CuDNa. These results indicate that Cu deficiency reduces NaCl tolerance in rats. Ultrastructural changes in kidney tissue and the suppression of RAAS in rats fed CuDNa suggest that the edema and ascites result from acute renal failure and not from increased fluid and electrolyte reabsorption.

Influence of dietary phosphorus and sulphaguanidine levels on P utilization in rats.

The effects of dietary phosphorus and sulphaguanidine levels, and sex differences on: (a) phytate digestibility, (b) calcium and P utilization, (c) the activities of alkaline phosphatase (EC 3.1.3.1), alkaline phytase (EC 3.1.3.8) and acid phosphatase (EC 3.1.3.2) in the intestinal mucosa of male and female rats were investigated. There was a linear increase in femur ash, Ca and P contents and the maximum force withstood by the fresh femurs as dietary P level was increased from 1.5 to 3.0 to 4.5 g/kg diet. The apparent digestibilities of Ca, P and phytate-P decreased as the level of P in the diet increased. Rats given the diets with 1.5 or 3.0 g P/kg were hypercalciuric and hypophosphaturic compared with rats receiving 4.5 g P/kg diet. The level of Ca retained was similar for all treatments. The level of P retained increased as the dietary P level increased. This suggests that P deprivation was a result of inadequate amounts of P retained and not due to the absorption of inositol phosphates formed during the enzymic hydrolysis of phytate. The addition of sulphaguanidine increased phytate digestibility without changing the activities of acid and alkaline phosphatase or alkaline phytase of the intestinal mucosa. This suggests that these enzymes did not play a role in the increase in phytate digestibility. However, dietary sulphaguanidine enhanced phytate digestibility, suggesting that alterations in the diet which modify either the composition or metabolism of the gastrointestinal microflora may be beneficial in enhancing the in vivo hydrolysis of phytate. Differences between males and females are reported and discussed.

Adaptive increase in phytate digestibility by phosphorus-deprived rats and the relationship of intestinal phytase (EC 3.1.3.8) and alkaline phosphatase (EC 3.1.3.1) to phytate utilization.

1. The effects of phosphorus deprivation on phytate digestibility, phosphorus utilization and intestinal phytase (EC 3.1.3.8) and alkaline phosphatase (EC 3.1.3.1) in rats were investigated. 2. P deprivation was achieved by giving rats a diet containing 3 g P/kg and resulted in hypophosphataemia, hypercalcaemia, hypercalciuria, and lower levels of P absorbed and retained, and calcium retained. 3. Rats adapted to P deprivation by increasing the digestion of total dietary-P and phytate-P. 4. Levels of intestinal alkaline phosphatase and alkaline phytase were not different between the two treatment groups. 5. P deprivation in the rats given the marginal-P diet may be a result of a lower absorption of total dietary-P or increased absorption of inositol phosphates formed during the enzymatic hydrolysis of phytate which are not readily utilized by the rat. 6. These results suggest that intestinal phytase and alkaline phosphatase do not play a role in the adaptive increase in phytate digestibility by rats given marginal-P diets. The adaptation may result from enhanced phytase or alkaline phosphatase synthesis by the gastrointestinal microflora stimulated by a lower level of P in the digesta.

Determinants and nature of intramuscular temperature changes during cold therapy.

The purpose of this study was to examine the intramuscular temperature response during an ice massage treatment. In addition, the effect of subcutaneous tissue thickness and limb circumference on temperature changes was investigated. Intramuscular temperature was measured by intramuscular thermocouples each minute during ice massage treatments of five, ten and fifteen minutes. It was shown that ice massage produces a significant drop in intramuscular temperature. However, there was no significant difference in temperature change after five minutes of treatment. In addition it was shown that there is a high multiple correlation between logarithmic time, subcutaneous tissue thickness, limb circumference, and intramuscular temperature change.