Cross-over study of fat-corrected forearm mineral content during nandrolone decanoate therapy for osteoporosis

We have previously reported an increase in forearm bone mineral content (BMC) during therapy for osteoporosis with the anabolic steroid, nandrolone decanoate. However, it has recently been claimed that part of this increase is spurious, due to a decrease in forearm fat during the treatment. We have therefore analyzed the data from a cross-over study of the effects of this agent on 70 osteoporotic women, using the fat correction procedure supplied by the manufacturer of the forearm densitometer. There was a significant rise (p less than 0.001) in the mean fat-corrected BMC (BMC[fc]) on nandrolone decanoate (50 mg intramuscularly every 2 or 3 weeks) and a non-significant fall in mean BMC[fc] off the drug. The mean time-weighted rate of change in the fat-corrected value was +29 +/- 5 mg/cm/year on nandrolone decanoate and -5 +/- 5 mg/cm/year off nandrolone decanoate (p less than 0.001). Nandrolone decanoate produces a significant gain in forearm mineral content even after allowing for changes in forearm fat content during therapy.     

The effects of nandrolone decanoate on nutritional parameters in hemodialysis patients

AIMS: Malnutrition with hypoalbuminemia is an independent predictor of mortality in end-stage renal disease patients. Anabolic steroids reduce protein catabolism and therefore may improve nutritional parameters. This study was undertaken to determine the effects of the anabolic steroid nandrolone decanoate on the nutritional status of hemodialysis patients. Secondary endpoints were to examine the effects of androgen therapy on hematocrit and erythropoietin (EPO) dose. PATIENTS AND METHODS: Medical records of chronic hemodialysis patients who received nandrolone decanoate for greater than 30 days were reviewed. Data collected included: demographics, dose, frequency, duration of treatment and cumulative dose of nandrolone. Baseline albumin, transferrin, dry weight, phosphorus, creatinine, hematocrit and erythropoietin dose were obtained for comparison with values after treatment. RESULTS: Of the 9 patients evaluated (mean +/- SD: age 55+/-28 years, 4/9 male), 2 patients received nandrolone doses of 25 mg intramuscularly (i.m.) every week, while the remaining 7 patients received 100 mg i.m. every 2 weeks. The mean +/- SD duration of treatment was 96+/-43 days, with a mean +/- SD cumulative dose of 656+/-371 mg. The mean +/- SD baseline albumin was 2.9+/-0.6 mg/dl which increased to 3.3+/-0.4 mg/dl after treatment (p = 0.045). Dry weight increased from a mean +/- SD of 64.4+/-11.7 kg to 66.0+/-10.9 kg after nandrolone therapy (p = 0.028). Mean +/- SD hematocrit at baseline was 28.2+/-4.5% and increased to 33.2+/-5.1% (p = 0.033). The dose of EPO was reduced in 4 patients (44%) during nandrolone therapy. CONCLUSIONS: Nandrolone significantly improved markers of nutritional status in our hemodialysis patients. This therapy may also enhance the hematopoietic effects of EPO.     

Complete replacement of methylprednisolone by azathioprine in cyclosporine-treated primary cadaveric renal transplant recipients

In cyclosporine (CsA)-treated renal transplant recipients complete corticosteroid withdrawal followed by CsA monotherapy has been associated with severe rejection episodes in a significant proportion of patients. We report the results of replacement of steroids by azathioprine (AZA) in 25 primary cadaveric renal transplant recipients initially treated with CsA and methylprednisolone (MP). MP taper was started 8.8 +/- 5.6 months posttransplant when the MP dose was either 10 mg/day or 20 mg every other day. MP was tapered off over a 5-month period. At the initiation of MP taper, AZA was added at 1 mg/kg/day and increased to 1.5 mg/kg/day after two months. The CsA dose was adjusted to maintain trough serum levels as measured by radioimmunoassay (RIA) of 50-75 ng/ml, during and after MP withdrawal. Seventeen patients have remained continuously off MP for 14.6 +/- 5.0 months with stable renal function. Reinstitution of MP at 10 mg/day was required in 8 patients, 6 for rejection (1.8 +/- 0.7 months after MP withdrawal), 1 for AZA-induced leukopenia, and 1 for de novo glomerulopathy. Renal function returned to baseline in all 6 patients with rejection after reinstitution of MP. Two of these patients have again been successfully retapered off MP. In the patients withdrawn from MP, body weight and mean arterial blood pressure had decreased by 2.1 +/- 1.3 kg (P less than .05) and 11 +/- 7 mmHg (P less than .05), respectively, at the time of the most recent follow-up compared with values at the initiation of steroid withdrawal. The number of blood pressure medications per patient decreased by 38% (P less than .05) and 6 patients were able to discontinue all antihypertensive drugs after cessation of steroids. Discontinuation of MP also resulted in a decrease in serum cholesterol concentration from 248 +/- 50 to 217 +/- 55 mg/dl (P less than .05). We conclude that steroids can be replaced by AZA in the majority of CsA-treated primary cadaveric renal transplant recipients by the end of the first posttransplant year without an adverse effect on graft survival. This protocol resulted in significant reductions in serum cholesterol, mean arterial blood pressure, and body weight, and may avoid the long-term side effects of steroid therapy.     

Effects of voluntary exercise on bone mineral content in rats

We used a voluntary running model to explore the relationship between average daily running distance and bone mineral status of rats. A total of 60 male Sprague-Dawley rats were randomly assigned at 6 weeks of age to a sedentary control group (n = 22) or to a group with unlimited access to a running wheel (n = 38). The running distance of exercising rats was monitored daily, and steady-state running levels ranged from 3.2 to 18.1 km/day. At the end of the experimental period, femora and tibiae were dissected and bone mineral content (BMC, g/cm) and bone mineral density (BMD, g/cm2) were measured by single-photon absorptiometry. Cross-sectional morphometry was examined by taking a transverse section of the femoral middiaphysis. Hindlimb percentage fat was significantly higher in controls than in runners (20.0 +/- 1.2 versus 11.1 +/- 0.6, p less than 0.001), and soleus mass was greater in runners than in controls (371 +/- 8.1 versus 320 +/- 0.8 mg, p less than 0.001). Femoral and tibial lengths, weights, and volumes were significantly higher in runners than in controls (p less than 0.005). BMC and BMD were higher in runners than in controls at all sites apart from the distal femur. Cross-sectional areas at the femoral midshaft were greater in running rats than in sedentary controls (6.26 +/- 0.1 versus 5.45 +/- 0.3 mm2, p less than 0.02), as was the polar moment of inertia (15.6 +/- 0.6 versus 12.7 +/- 0.2 mm4, p less than 0.05). No positive correlation was found between distance run and BMC, BMD, cross-sectional area, or polar moment of inertia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Does 1 alpha(OH)D3 treatment affect blood pressure levels in maintenance hemodialysis patients?

Forty-eight chronic hemodialysis patients were divided comparably into two groups (24 patients in each). Two micrograms of 1 alpha(OH)D3 was administered to one group for 3 months and its placebo to the other group. In the 1 alpha(OH)D3-treated group, serum total calcium increased from 7.82 +/- 0.11 (mean +/- SEM) to 9.70 +/- 0.27 mg/dl (p less than 0.001) which was significantly higher (p less than 0.001) than control values of 8.86 +/- 0.06 mg/dl from normal volunteers. Systolic, diastolic and mean blood pressures, however, did not change significantly throughout the study. Even in the 9 patients who had a substantial increment of serum calcium of more than 2 mg/dl with hypercalcemia (greater than 10 mg/dl) at 3 months, no significant changes in blood pressure were found. Serum iPTH decreased from 2.83 +/- 0.28 to 0.98 +/- 0.23 ng/ml (p less than 0.001) at 3 months of treatment. Furthermore, a significant inverse correlation was obtained between the changes in serum calcium and iPTH. In the placebo group there were no significant changes in serum calcium, iPTH and blood pressure during the 3-month treatment period. The present study indicates that a substantial increase in serum calcium or a chronic hypercalcemia induced by 1 alpha(OH)D3 treatment in maintenance hemodialysis patients does not accompany a rise in blood pressure, probably due to a concomitant suppression of PTH. The results also suggest that the hypocalcemic state found in hemodialysis patients is not associated with any significant change in blood pressure. The importance of PTH in blood pressure regulation was discussed.     

Low-dose aspirin protects against lipid accumulation in primate vein bypass grafts

Platelet inhibition with high-dose aspirin combined with dipyridamole reduces lipid accumulation and improves early patency of coronary artery bypass grafts. However, recent evidence suggests that platelet inhibition can be achieved with substantially lower aspirin doses than have been conventionally prescribed. To evaluate whether low-dose aspirin protects against lipid accumulation in bypass grafts, we studied 15 stump-tailed macaque monkeys in which autologous cephalic veins were grafted into the femoral arteries. A control group received no treatment, a second group was treated with a low, single daily dose of aspirin (12 mg), and a third group was given a higher dosage of aspirin (80 mg/day) combined with dipyridamole (50 mg/day) divided into two daily doses. A special diet was fed that resulted in plasma cholesterol levels (224 +/- 50 mg/dl, mean +/- standard deviation) and plasma lipoprotein distributions that mimic the profile in humans. Cholesterol concentration in grafts removed 3 months after insertion was 0.47 +/- 0.12 mg/100 mg tissue in the control group; it was reduced to 0.23 +/- 0.04 mg/100 mg (p less than 0.001) by low-dose aspirin and to 0.17 +/- 0.05 mg/100 mg (p less than 0.001) by combined aspirin and dipyridamole therapy. Graft apolipoprotein B concentration was 66 +/- 19 micrograms/100 mg in control group; it was reduced to 40 +/- 8 micrograms/100 mg (p less than 0.05) by low-dose aspirin and to 23 +/- 7 micrograms/100 mg (p less than 0.001) with the combination treatment. There were no differences between groups in either cholesterol concentration (0.09 +/- 0.02 mg/100 mg) or apolipoprotein B concentration (10 +/- 3 micrograms/100 mg) in normal ungrafted vein. Platelet function tests demonstrated platelet aggregation in all control monkeys, in none of the combined therapy group, and in two of five monkeys receiving low-dose aspirin. This study indicates that low-dose aspirin is protective against graft lipid accumulation in monkeys. The mechanism of this antilipid effect and its relation to any antithrombotic effect remain to be elucidated.     

Long-term minoxidil treatment in refractory hypertension and renal failure

Twenty-two patients with severe or accelerated hypertension refractory to conventional hypotensive therapy have been treated with minoxidil for an extended period. Patients were divided in three groups according to different degrees of renal function or the presence of accelerated hypertension. In the first group (8 patients with normal or slightly decreased renal function) BP fell from 197 +/- 11/118 +/- 3 before minoxidil therapy to 157 +/- 7/98 +/- 2 after six months (p less than 0.001), and remained steady during the following eighteen months. In the second group (9 patients with creatinine clearance of 30 +/- 3 ml/min.1.73 m2) BP decreased from 192 +/- 9/119 +/- 4 to 147 +/- 6/91 +/- 4 at six months (p less than 0.001); renal function did not show any significant modification during the eighteen months of the study. In the third group (5 patients with accelerated hypertension) BP fell from 243 +/- 14/137 +/- 6 to 166 +/- 13/99 +/- 7 at six months (p less than 0.01). Seven patients, four in the first and three in the second group, were followed for more than six years; these patients, with mild renal insufficiency (creatinine clearance 50 +/- 4 ml/min) before minoxidil therapy, were on a protein unrestricted diet for the entire length of the study. In this group of patients BP fell from 182 +/- 9/115 +/- 3 to 150 +/- 6/96 +/- 2 after one year (p less than 0.01) and remained well controlled for the following six years or more. Renal function did not show any significant worsening over the years (monthly decrement in creatinine clearance 0.08 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

A short course of recombinant human growth hormone treatment stimulates osteoblasts and activates bone remodeling in normal human volunteers

The effects of recombinant human growth hormone (rhGH) on biochemical markers of bone turnover and bone mineral content (BMC) were investigated in 20 normal male volunteers (aged 22-31 years) randomized to treatment for 7 days with either rhGH (0.1 IU/kg subcutaneously twice a day) or placebo. Serum somatomedin C rose during treatment (p less than 0.001) but was not significantly different from baseline at day 14. The fasting urinary hydroxyproline/creatinine (p less than 0.001) and calcium/creatinine ratios (p less than 0.01) increased during treatment and remained elevated for 4 and 2 weeks, respectively. Serum bone gamma-carboxyglutamic acid-containing protein (BGP) increased during treatment (p less than 0.001) and remained elevated for 6 months (p less than 0.02). Serum bone alkaline phosphatase (B-AP), after an initial fall in the treatment period (p less than 0.001), increased slightly in the following months (p less than 0.01). In the rhGH group BMC was significantly higher than the prestudy value at day 14 (p less than 0.05) but was unaltered at the end of study. The simultaneous increase in markers of bone resorption and formation during rhGH treatment followed by a decline in resorption parameters within a few weeks and the prolonged effect on BGP and B-AP demonstrate that rhGH treatment stimulates osteoblasts and activates bone remodeling.     

Long-term effects of calcium carbonate and 2.5 mEq/liter calcium dialysate on mineral metabolism

Many investigators have shown that calcium carbonate (CaCO3) is an effective phosphate binder which also prevents the potential disabling effects of aluminum (Al) accumulation. However, hypercalcemia may develop in a substantial numbers of patients. Thus, to control serum phosphate (PO4) and prevent hypercalcemia, we performed studies in 21 patients on maintenance hemodialysis in which, in addition to the oral administration of CaCO3, the concentration of calcium (Ca) in the dialysate was reduced from 3.25 to 2.5 mEq/liter. The studies were divided in three periods: I. control, on Al-binders (one month); II. no Al-binders (one month); III. CaCO3 (seven months). Blood was obtained three times/week before dialysis for the first five months of the study and once a week for the remaining four months. During the control period, the mean serum calcium was 8.86 +/- 0.08 mg/dl. The value decreased to 8.65 +/- 0.07 mg/dl when phosphate binders containing aluminum were discontinued, and increased to 9.19 +/- 0.07 mg/dl (P less than 0.001 compared to period II) during oral supplementation with calcium carbonate. The mean serum phosphorus was 5.03 +/- 0.07 mg/dl during the control period, and increased to 7.29 +/- 0.91 mg/dl (P less than 0.001) after phosphate binders were discontinued. It decreased to 4.95 +/- 0.06 mg/dl (P less than 0.001) with the administration of calcium carbonate. During CaCO3 administration, serum Al decreased from 64.2 +/- 8.5 to 37.1 +/- 3.6 and 25.1 +/- 3.0 micrograms/liter (P less than 0.001) at three and seven months, respectively. Serum parathyroid hormone (PTH) decreased by 20%.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of megestrol acetate, nandrolone decanoate and dietary counselling for HIV associated weight loss

This randomized, prospective study compared three treatments, nandrolone decanoate (ND), megestrol acetate (MA) or dietary counselling, for managing human immunodeficiency syndrome (HIV) associated weight loss. It was centred on a Tertiary referral hospital, Sydney, Australia. Fifteen patients were randomized to receive ND (100 mg/fortnight), or MA (400 mg/day) or dietary counselling for 12 weeks. Those patients randomized to dietary counselling were further randomized to receive nandrolone or megestrol after completing the dietary counselling arm. Weight, fat free mass (FFM), percentage body fat mass (FM), dietary intake and appetite were assessed before commencing and at the completion of each treatment arm. Weight increased significantly in all treatment arms (dietary counselling 1.13 kg +/- 0.36, nandrolone 4.01 kg +/- 1.68, megestrol 10.20 kg +/- 4.51, p < 0.05 paired t-test). FFM increased significantly in patients receiving ND (3.54 +/- 1.98 kg, p=0.001) and those receiving MA (2.76 +/- 0.55 kg, p=0.002), whereas the change in those receiving dietary counselling alone was not significant. Percentage body fat mass increased significantly only in those receiving MA (7.77 +/- 4.85%, p=0.049). The change in weight and percentage body fat mass was significantly greater in those receiving MA than the other two treatment arms. The increase in FFM was significantly greater in both the nandrolone and megestrol arms than the dietary counselling arm. It was concluded that ND and MA both resulted in an increase in FFM greater than dietary counselling alone. Megestrol produced a significantly greater increase in weight, percentage fat mass, intake and appetite than did the other two treatment arms, suggesting it may be the preferred agent, particularly in a palliative care setting in which weight, appetite and intake increase are desirable without regard to the composition of the body. The long-term use of these agents in people with HIV should be reviewed in the context of improved survival on highly active antiretroviral therapy regimens.     

Homologous growth hormone accelerates healing of segmental bone defects

The effect of homologous recombinant porcine growth hormone (r-pGH) on secondary fracture healing was investigated in a diaphyseal defect of the tibia in Yucatan micropigs. A 1 cm defect of the tibia was created surgically and stabilized with an AO 3.5 mm DCP plate. The treatment group (12 animals) received 100 microg of r-pGH per kilogram of body weight subcutaneously once per day, whereas the control pigs (12 animals) received 1 mL of sodium chloride as placebo. For evaluation of the GH-axis, serum levels of insulin-like growth factor-I (IGF-I) were sampled every fourth day. The animals were killed 6 weeks after surgery. Quantitative computed tomography (qCT) was performed to determine bone mineral density (BMD) and bone mineral content (BMC) of the defect zone. The torsional stiffness and the torsional failure load were measured by destructive torsional testing of the defect and contralateral tibiae. qCT measurements revealed a significant increase in the BMC of the defect zone in the treatment group compared with controls (GH BMC = 2833 +/- 679 mg, placebo BMC = 2215 +/- 636 mg; p < 0.05), whereas the BMD values were similar in both groups (GH BMD = 668 +/- 60 mg/mm(2), placebo BMD = 629 +/- 52 mg/mm(2), p = 0.12). Torsional failure load was 70% higher and torsional stiffness 83% higher in the treatment group than in the control group (p < 0.05). The mean serum level of IGF-I in the treatment group increased to 382% of the preoperative basal level and decreased to 69% in the control group, and this difference was highly significant (p < 0.001). Our data indicate that daily administration of recombinant GH leads to an increase of serum IGF-I levels and stimulates secondary fracture healing, resulting in increased mechanical strength and stiffness of the callus.     

Long-term follow-up after cyclophosphamide and cyclosporine-A therapy in steroid-dependent and -resistant nephrotic syndrome

A retrospective study was made on 37 children with idiopathic nephrotic syndrome (INS). At the beginning, all patients were steroid sensitive but received more than one steroid course (median 4). Following several relapses, they became steroid dependent or steroid resistant. Group 1 consisted of 22 children [3 focal segmental glomerulosclerosis (FSGS), 19 minimal-change NS (MCNS)] who received cyclophosphamide (CP) orally for 2.5 +/- 0.5 months. Group 2 consisted of 15 children (7 FSGS, 8 MCNS) who received cyclosporine-A (CSA) for 28 +/- 15 months. The level of proteinuria decreased significantly and remained low during the follow-up. The relapse-free period was significantly longer in the CP group (CP 30 +/- 21.5; CSA 26.2 +/- 18 months, p < 0.001). The relapse rate decreased significantly in both groups and remained in this lower level during the follow-up (from 3.4 +/- 2.8 to 0.1 +/- 0.2/year in group 1, and from 3.7 +/- 3.1 to 0.6 +/- 0.8/year in group 2). At the end of the 5-year follow-up, 20/22 patients (90.9%) and 10/15 patients (66.6%) were in remission in groups 1 and 2 respectively, with or without treatment (p < 0.05). In the long term, both CP and CSA is effective second-line therapy following steroid monotherapy in INS patients, but the relapse rate was lower and the relapse free period was significantly longer in the CP-treated group.     

The effects of growth hormone replacement therapy on bone metabolism in adult-onset growth hormone deficiency: a 2-year open randomized controlled multicenter trial.

Adult hypopituitary patients with growth hormone deficiency (GHD) show a significant decrease in bone mass and an increased fracture rate. Replacement therapy with GH increases bone turnover. Most of the long-term data on bone mineral content (BMC) and bone mineral density (BMD) have been acquired in open, noncontrolled trials involving limited numbers of patients. To determine whether long-term GH therapy is beneficial for bone despite the increased bone turnover, 100 patients (59 men and 41 women), aged 25-65 years (mean, 49.7 years) with adult-onset GHD were randomized to treatment with GH (40 men and 28 women; mean dose, 0.18 IU/kg per week) or to a nontreated control group (19 men and 13 women) for 24 months. Despite a similar increase in parameters of bone turnover (osteocalcin [OC], procollagen type I carboxy-terminal propeptide [PICP], and pyridinolines ([PYD]) in male and female GH-treated patients compared with controls, the effects on BMC and BMD as evaluated by dual-energy X-ray absorptiometry were gender specific. A significant increase in spine BMC and BMD and total hip BMD and a decrease in BMD at the ultradistal radius over time was observed in male GH-treated patients compared with the evolution in controls (mean +/- SEM change at 24 months: +6.8 +/- 1.1% and p = 0.009, +5.1 +/- 0.8% and p = 0.005, +3.5 +/- 0.7% and p = 0.02, and -2.6 +/- 0.8% and p = 0.008, respectively). No significant treatment effects were observed in female patients. Despite the increase in the total remodeling space induced by GH treatment, prolonged GH therapy in adult-onset GHD has a positive effect on bone balance, maintaining bone mass in women, and even increasing it in men over a 2 year-period.     

The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: a randomized study comparing intermittent treatment and an ADFR regime

Thirty-seven patients were randomized to receive intermittent cyclic etidronate (400 mg/day oral for 2 weeks, followed by 13 weeks off treatment) or an ADFR treatment (100 micrograms/day oral triiodothyronine for 7 days, followed by 400 mg/day etidronate for 2 weeks and 12 weeks off treatment). Supplemental calcium (120 mg/day) and vitamin D3 (400 IU/day) were given throughout the study period to all patients. Biochemical analyses, iliac-crest bone biopsies, and lumbar bone mineral content (BMC) measurements were performed before and during 60 weeks of treatment. Sixteen patients in the intermittent cyclic etidronate group and 15 in the ADFR group completed 60 weeks of treatment. Serum alkaline phosphatase decreased from 185 (43) (mean, (SD] to 144 (35) (p less than 0.001) and from 221 (69) to 156 (43) (p less than 0.002) during intermittent cyclic etidronate treatment and ADFR treatment, respectively, without any significant changes in renal hydroxyproline excretion. Final resorption depth, trabecular bone activation frequency, and bone formation rate decreased significantly from 51.5 (48.4/60.0) microns (median (25%/75% quartiles] to 44.0 (39.6/46.2) microns (p less than 0.04), from 0.30 (0.17/0.62) year-1 to 0.10 (0.02/0.19) year-1 (p less than 0.03) and from 0.035 (0.020/0.081) microns3/microns2/day to 0.015 (0.002/0.025) microns3/microns2/day, p less than 0.03 respectively, during intermittent cyclic etidronate treatment, but were unchanged during ADFR treatment. No significant changes in trabecular bone volume, bone balance per remodeling cycle, or BMC were noted in either treatment group; no evidence of osteomalacia was found. Intermittent cyclic etidronate treatment may be effective in preventing bone loss and in decreasing the risk of trabecular plate perforation, and thereby maintaining the integrity of bone architecture, in postmenopausal osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lovastatin in the treatment of hypercholesterolemia in nephrotic syndrome due to diabetic nephropathy stage IV-V.

The efficacy and safety of lovastatin, a drug for lowering hypercholesterolemia, have been evaluated in ten adult patients with insulin-dependent diabetes mellitus (IDDM) and nephrotic syndrome due to diabetic nephropathy stage IV or V of Mogensen. For the first 8 weeks the patients received only a sugar-free isocaloric diet of which fats supplied approximately 30% of the total caloric intake and with not more than 300 mg cholesterol daily. After this run-in period patients were treated with 20 mg lovastatin once daily for 12 weeks while receiving the same isocaloric diet as previously. Body weights and glycosylated hemoglobin concentrations (HbAlc) did not change significantly during this period. The baseline plasma cholesterol concentrations (mean +/- SD) decreased only by 2% (from 310 +/- 54 to 303 +/- 46 mg/dl) during the 8 weeks with low cholesterol diet and by 25% (from 303 +/- 46 to 228 +/- 38 mg/dl) during the 12-week period on lovastatin therapy (p less than 0.005). The mean concentrations of low-density lipoprotein (LDL-)-cholesterol decreased by 3% (from 218 +/- 53 to 211 +/- 52 mg/dl) during the diet period and by 35% (from 211 +/- 52 to 137 +/- 38 mg/dl) during the period with lovastatin therapy (p less than 0.001). Concentrations of high-density lipoprotein (HDL) cholesterol increased slightly (11%) during the therapy with lovastatin (NS). Baseline plasma triglycerides fell by 22% (from 188 +/- 97 to 146 +/- 59 mg/dl) during the period with fat-restriction (p less than 0.05) and by 13% (from 146 +/- 59 to 127 +/- 54 mg/dl) during the period of lovastatin therapy (NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical assessment of low-dose steroid therapy for patients with IgA nephropathy: a prospective study in a single center

BACKGROUND/AIM: No accepted therapy has been established for progressive IgA nephropathy (IgAN). The purpose of the present study was to assess low-dose steroid therapy in the treatment of patients with IgAN. METHODS: A prospective trial of low-dose steroid therapy was performed in patients with IgAN with mild histological activities. Twenty-four patients in the steroid group and 24 patients in the control group were included in this study. The initial dose of prednisolone was 0.4 mg/kgBW/day (20-30 mg/day), gradually tapered to 5-10 mg/day over 24 months. The patients with mild active inflammatory lesions were treated with prednisolone. The patients assigned to the control group were treated with dipyridamole or zilazep hydrochloride in a dose of 150 or 300 mg/day. RESULTS: In all of the patients studied, serum creatinine levels did not significantly change over 24 months. However, daily proteinuria significantly reduced after 24 months of steroid therapy (0.97 +/- 0.75 vs. 0.31 +/- 0.51 g/day, P = 0.0012), even if did not change after 24 months of anti-platelet drugs (0.89 +/- 0.49 vs. 0.68 +/- 0.69 g/day, P = 0.2289), respectively. In addition, the grade of hematuria significantly reduced after 24 months of steroid therapy (35.6 +/- 36.3 RBC/HPF vs. 13.7 +/- 28.4 RBC/HPF, P = 0.0249) and 24 months of anti-platelet drugs (30.1 +/- 37.1 RBC/HPF vs. 12.4 +/- 20.3 RBC/HPF, P = 0.0465), respectively. Systolic and diastolic blood pressures did not significantly change during treatment with steroid or anti-platelet drugs. Vascular changes (0.63 +/- 0.73) in the steroid group were lower than those (1.08 +/- 0.88) in the control group (P = 0.008). CONCLUSION: Our data suggested that low-dose steroid therapy for IgAN patients with mild inflammatory lesions could reduce the amount of urinary protein excretion and prevent deterioration of renal function, provided the histological findings in the renal biopsies showed mild vascular lesions.     

Renal handling of beta-2-microglobulin in neonates treated with gentamicin

Increased levels of urinary beta 2-microglobulin (beta 2M) have been used as a marker of proximal tubular dysfunction in human neonates. To assess the value of beta 2M in the detection of early stages of tubular damage caused by gentamicin, renal handling of beta 2M was studied sequentially in 18 gentamicin-treated neonates with idiopathic respiratory distress syndrome (mean birth weight 1,781 g, mean gestational age 33.7 weeks) during the first 7 days of life. These data were compared with those obtained from 10 control infants matched for gestational and postnatal ages. In addition, follow-up studies of renal function were conducted in 14 of 18 study infants 1 week after termination of therapy, on day 14 postpartum. The (+/- SD) fractional tubular excretion of beta 2M (FE beta 2M) tended to decrease significantly in the control infants from 10.3 +/- 1% on day 1 to 6.5 +/- 0.8% on day 7 postpartum (p less than 0.05). In infants treated with gentamicin, the mean FE beta 2M rose from 10.5 +/- 2% on day 1 to 17.1 +/- 1% on day 7 (p less than 0.01), followed by a decrease to 8.2 +/- 0.5% over the next 7 days (p less than 0.001). Compared with the control infants, values for the infants receiving gentamicin were significantly higher on postpartum days 3,5, and 7 (p less than 0.001). No significant differences in serum creatinine, creatinine clearance, or fractional tubular excretion of sodium were observed between the two groups during the study period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Corticosteroid therapy in patients with IgA nephropathy and impaired renal function

AIM: IgA nephropathy (IgAN) is a common type of primary glomerulonephritis that constitutes a major cause of end-stage renal disease. Oral and/or intravenous glucocorticoid therapy can protect against progression of IgAN in patients with preserved renal function. We evaluated steroid therapy in IgAN with established renal dysfunction. PATIENTS AND METHODS: We retrospectively analyzed the effect of methylprednisolone (MP) pulse therapy in 8 IgAN patients with serum creatinine concentrations (sCr) 2.76 +/- 1.32 mg/dl (mean +/- SD). In each patient renal function had progressively deteriorated in the 12 months preceding treatment, as indicated by negative slopes of 1/sCr plotted against time (regression coefficients). RESULTS: Regression coefficients during the 12 months following therapy improved significantly from -0.02333 +/- 0.00732 to -0.00036 +/- 0.00423 dl/mg/month, respectively. The mean difference in slope was 0.0230 +/- 0.0076 dl/mg/month (95% confidence interval, 0.0165 to 0.0295, p < 0.001). Proteinuria also significantly decreased from a mean urine protein/creatinine ratio of 2.57 +/- 1.12 before therapy to 1.12 +/- 0.84 6 months after therapy (p < 0.005). Other factors that might affect progression of renal dysfunction remained unchanged during the observation periods. CONCLUSION: Corticosteroids may attenuate progression of renal failure and delay the need for dialysis in this patient population, although a large randomized trial is necessary.     

THE EFFECT OF AN ANABOLIC STEROID ON BODY COMPOSITION IN PATIENTS RECEIVING INTRAVENOUS NUTRITION

In this controlled trial we investigated the effect of an anabolic steroid, in terms of the changes in body composition that occurred in ill surgical patients requiring intravenous nutrition. Glucose was the sole non-protein energy source. The study was conducted over a 14-day study period in two comparable groups of 13 patients. The changes in body weight, fat, protein and water were measured. The control group received a nutrient solution of hypertonic dextrose and amino acids (44.8 ± 8.2 kcal/kg/day), and the comparative group received the same solution (44.3 ± 5.2 kcal/kg/day) and 100 mg of an intramuscular injection of nandrolone decanoate at the commencement of the study and again one week later. Over the two-week study period both groups gained body weight. In the controls this was composed of fat (0.4 kg) and water 1.5 kg). In the anabolic steroid group, weight gain was mainly water, and fat gain did not occur. Neither group gained body protein. Diuretic therapy was required more often (21 patient days compared with 5 patient days; p > 0.001) in the anabolic steroid group to control excessive water retention. Our study has shown no benefit from an anabolic steroid when given in combination with a 14-day course of intravenous nutrition. Water retention was more of a problem with this therapy.     

The role of prostaglandin E in the hemodynamic response to aortic clamping and declamping.

The infrarenal aorta was occluded for one hour in 11 control dogs and in eight dogs in which biosynthesis of prostaglandin E (PGE) was inhibited by administration of indomethacin (2.5 mg. per kilogram). The mean arterial pressure (MAP) in the indomethacin group was significantly (p less than 0.001) higher than in the control group at the end of 60 minutes of aortic occlusion (187 +/- 3 vs. 137 +/- 4 mm. Hg, mean +/- S.E.M.) and remained higher (p less than 0.001) after declamping. However, the decline in MAP at the time of aortic declamping was essentially the same for both groups. Total peripheral resistance (TPR) was higher in the indomethacin group than in the control group at the end of one hour of occlusion (159 +/- 13 vs. 124 +/- 12%, p less than 0.001) and remainded higher throughout the period following occlusion. The plasma concentration of PGE in the control group increased significantly (p less than 0.05) above control (630 +/- 110 to 1,299 +/- 261 pg. per milliliter) during the 60 minute period of occlusion with further increases to 1,447 +/- 389 and 1,523 +/- 256 pg. per milliliter (p less than 0.001) at 10 and 60 seconds after declamping, respectively. In the indomethacin group, PGE remained essentially unchanged throughout the clamping and declamping period and therefore was significantly (p less than 0.05) lower than in the control group. A similar pattern was observed in the tissue levels of PGE. This study suggests that PGE is released during and after infrarenal aortic occlusion and may be responsible for maintaining reduced TPR and MAP. However, hypotension after declamping is not affected by inhibition of PGE biosynthesis.