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Biomedical subjects

F Llach

Publications and source records attributed to F Llach.

At least 55 records · Page 3Linked to original sources
PubMed1989

The evolution of osteomalacia in the rat with acute aluminum toxicity.

Aluminum toxicity is the presumed cause of aluminum-associated osteomalacia. In animal models, osteomalacia has been produced after a prolonged course of aluminum. In the present study, rats with renal failure received 20 mg intraperitoneal aluminum during a 2 day period. This model allows sequential observations in the development of osteomalacia. Rats were sacrificed and studied 5, 12, 25, and 40 days after aluminum administration. No differences were observed in serum calcium, phosphorus, or creatinine as a consequence of aluminum administration. Compared with control rats, parathyroid hormone was decreased at 12 and 25 days. A direct correlation was present between plasma and bone aluminum at 12 days (r = 0.92, p less than 0.01), 25 days (r = 0.85, p less than 0.005), and 40 days (r = 0.88, p less than 0.001) but not 5 days after aluminum administration. Plasma aluminum peaked at 5 days (727 +/- 89 micrograms/liter, mean +/- SEM) and bone aluminum at 40 days (273 +/- 40 micrograms/g). Aluminum had profound effect on bone histology. At 5 days there was a decrease in osteoblast surface and osteoid surface; at 12 days osteoblast surface and osteoid surface returned to normal but osteoclast surface decreased. Subsequently there was a progressive increase in osteoid surface and osteoid volume. Bone formation rate measured at 12, 25, and 40 days was decreased at these intervals. In conclusion, (1) high plasma aluminum may be directly toxic to the osteoblast; (2) progressive osteoid accumulation is secondary to matrix (osteoid) deposition, which exceeds the depressed bone formation rate; (3) the progressive decrease in plasma aluminum and increase in bone aluminum suggest that bone has a high affinity for aluminum but may have a relatively slow rate of uptake at any given time; (4) aluminum may directly decrease parathyroid hormone; (5) the correlation between plasma and bone aluminum suggest an exchange is present; and (6) aluminum toxicity may independently affect the osteoblast and bone mineralization.

Aluminum↗
PubMed1989

Association between aluminum accumulation and cardiac hypertrophy in hemodialyzed patients.

In order to investigate the possible role of aluminum accumulation on the myocardium, 50 stable asymptomatic hemodialysis patients were studied. Patient cardiac status was assessed by echocardiography. A deferroxamine (DFO) test, together with a bone biopsy, was performed to determine the magnitude of AI accumulation. Thus, an increase in serum AI after DFO (delta AI DFO) and stainable cortical bone aluminum (SCBA) were taken as parameters of AI load. Fourteen of 50 patients had no SCBA. They differed from the 36 patients with SCBA in that they had lower left ventricular mass (LVM) (P less than 0.001), increased velocity of circumferential fiber shortening (Vcf) (P less than 0.001), and higher mitral E-F slope (P less than 0.01). In the overall population there was a mild increment in serum AI and in delta AI DFO. The duration of dialysis treatment was correlated with SCBA and delta AI DFO (P less than 0.001). A correlation was observed between LVM and delta AI DFO (P less than 0.001) and between LVM and SCBA (P less than 0.001). Multivariate correlations analysis indicated that these relationships were independent of the duration of dialysis treatment. The present data suggest that, in hemodialysis patients aluminum accumulation may be associated with increased LVM.

Adult↗
PubMed1989

Deferoxamine test and bone disease in dialysis patients with mild aluminum accumulation.

Aluminum bone disease is a frequent complication of dialysis patients. The deferoxamine (DFO) test has been advocated as a noninvasive procedure for the diagnosis of AI bone lesion. However most of these studies have been performed in symptomatic patients with significant AI bone disease. Whether this test may provide similar data at an earlier stage of AI toxicity is not known. The present study evaluates prospectively 28 patients with mild AI load. Patients studied ranged in age from 21 to 65 years; duration of dialysis was 5.6 +/- 3.2 years; deferoxamine, 40 mg/kg body weight, was infused at the end of dialysis. Serum AI was measured before DFO administration and before the next dialysis treatment. Bone biopsies were performed in all patients. Cortical bone AI was determined biochemically; trabecular and cortical bone AI were also determined histochemically. Mean basal serum AI (43.2 +/- 30.8 micrograms/L) and cortical bone AI (25.7 +/- 35.2 micrograms/g) were moderately increased. Basal serum AI correlated (r = 0.77) with the increment in serum AI after DFO infusion. After DFO, stainable trabecular and cortical bone AI correlated in a similar manner with both basal serum AI and increment in serum AI. Only biochemically determined cortical bone AI was not significantly related to basal serum AI. Nineteen of the 28 patients had evidence of osteitis fibrosa on bone biopsy. Stained AI surfaces but not trabecular AI were different in patients with low and patients with high bone formation rates. The bone findings, assessed as bone formation rates and resorption surfaces, did not correlate with biochemically or histochemically determined bone AI.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1989

Desferrioxamine therapy in hemodialysis patients with aluminum-associated bone disease.

Aluminum toxicity in dialysis patients is associated with decreased bone turnover and a relative parathyroid hormone (PTH) deficiency. Desferrioxamine (DFO), a chelating agent, has been reported to improve bone histology in aluminum associated, low turnover bone disease in dialysis patients not subjected to parathyroidectomy. Information on the effect of DFO therapy on parathyroid gland function is lacking. In the present study, in addition to changes in bone histology, parathyroid gland function was evaluated in 18 hemodialysis patients with aluminum associated, low turnover bone disease (osteomalacia and aplastic bone disease) before and after one year of DFO treatment (1 to 6 g/week). Parathyroid gland function was assessed by using a calcium free and high calcium (3.5 to 4 mEq/liter) hemodialysis bath.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1989

Direct inhibitory effect of calcitriol on parathyroid function (sigmoidal curve) in dialysis.

The effect of intravenous calcitriol on parathyroid function was evaluated in nine chronic hemodialysis patients with secondary hyperparathyroidism. Two micrograms of calcitriol were administered intravenously after dialysis thrice weekly for ten weeks. Parathyroid function was assessed by inducing hypo- and hypercalcemia with low calcium (1.0 mEq/liter) and high calcium (4.0 mEq/liter) dialyses before and after ten weeks of intravenous calcitriol therapy. To avoid hypercalcemia during calcitriol administration, the dialysate calcium was reduced to 2.5 mEq/liter. Parathyroid hormone (PTH) values (pg/ml) from dialysis-induced hypo- and hypercalcemia were plotted against serum ionized calcium, and the sigmoidal relationship between PTH and calcium was evaluated. Basal PTH levels fell from 902 +/- 126 pg/ml to 466 +/- 152 pg/ml (P less than 0.01) after therapy without a significant change in the serum total calcium concentration. The ionized calcium-PTH sigmoidal curve shifted to the left and downward after calcitriol therapy. The maximal PTH response during hypocalcemia decreased after calcitriol from 1661 +/- 485 pg/ml before calcitriol to 1031 +/- 280 pg/ml afterward (P less than 0.05). The PTH level at maximal inhibition due to hypercalcemia decreased from 281 +/- 76 pg/ml before calcitriol to 192 +/- 48 pg/ml afterward (P less than 0.05). The slope of the sigmoidal curve changed from -2125 +/- 487 to -1563 +/- 385 (P less than 0.05). The set point of ionized calcium (4.60 +/- .11 mg/dl before vs. 4.44 +/- .07 mg/dl after) did not change significantly with calcitriol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗
PubMed1989

Relationships between histomorphometric features of bone formation and bone cell characteristics in vitro in renal osteodystrophy.

To determine whether abnormal bone cell recruitment or differentiation may be involved in the development of aplastic bone lesion in renal osteodystrophy we have compared histomorphometric parameters of bone formation and in vitro behavior of osteoblastic cells isolated from the trabecular bone surfaces in 37 dialysis patients with osteitis fibrosa, normal bone formation rate, or aplastic bone lesion. The bone cell responses to human PTH-(1-34) (20 nmol/L), as evaluated by intracellular cAMP production, and to 1,25-dihydroxyvitamin D (10 nmol/L), as assessed by osteocalcin synthesis, were not different from normal in patients with low, normal, or high bone formation rates. Osteoblastic cells isolated from patients with a high bone formation rate and markedly elevated serum iPTH and osteocalcin values had a higher than normal DNA replication in primary culture. The peak of [3H]thymidine incorporation, the maximal DNA synthesis, and the area under the growth curve were 4.4- to 6.3-fold increased in osteitis fibrosa compared to those in normal bone cells obtained from age-matched individuals. By contrast, [3H]thymidine incorporation in bone cells from aplastic patients was about 25% of normal and only 5% of the value in osteitis fibrosa. The decreased DNA replication of cultured bone cells in aplastic patients was unrelated to trabecular bone aluminum staining, but was associated with low serum immunoreactive PTH values compared to those in other groups of patients. These results show that high bone formation in uremic osteoitis fibrosa is associated with higher than normal [3H]thymidine incorporation in bone cells in vitro, whereas low bone formation in aplastic patients results from lower than normal DNA replication and suggest that the defective osteoblastic recruitment in aplastic patients may be related to factors other than aluminum, including inappropriate PTH secretion.

Biopsy↗
PubMed1988

Arginine-induced hypermagnesemia and hyperkalemia in nephrectomized rats.

This study examined the effect of arginine monohydrochloride infusion on serum Mg and K in nephrectomized rats. Hyperkalemia exceeded the hypermagnesemia both of which occurred in response to arginine infusion and/or metabolic acidosis. This observation is consonant with our earlier reports which demonstrated that the activity of K exceeded that of Mg in shifts between the intracellular and extracellular compartments under a variety of experimental conditions.

Acidosis↗
PubMed1987

Secondary hyperparathyroidism and cardiac hypertrophy in hemodialysis patients.

Echocardiographic assessment of left ventricular function was performed in 66, stable hemodialysis patients and 50 normal controls matched for sex, age and arterial blood pressure. On the basis of bone histology, hemodialysis patients were classified into two groups: (1) patients with normal bone resorption; and (2) patients with active secondary hyperparathyroidism characterized by an increased bone resorption. Left ventricular function of these two subgroups were compared together as well as with the echocardiographic characteristics of normal controls. In comparison with normal controls, hemodialysis patients with normal bone resorption had an increased left ventricular volume (P less than 0.001) and left ventricular mass (P less than 0.001) with a similar left ventricular mass-to-volume ratio. Their systolic arterial pressure--mass-to-volume ratio correlation was similar to that of normal controls, indicating an adequate myocardial hypertrophy. Patients with increased bone resorption had high parathormone and alkaline phosphatase levels; though the left ventricular dilation was similar to that of hemodialysis patients with normal bone resorption, the left ventricular mass was lower (P less than 0.001) and was similar to the left ventricular mass of normal controls. In addition, patients with increased bone resorption had a lower mass-to-volume ratio (P less than 0.001) and their systolic arterial pressure--mass-to-volume ratio correlation exhibited a significant downward shift (P less than 0.001), suggesting an inadequate myocardial hypertrophy. Patients with increased bone resorption and secondary hyperparathyroidism had an increased heart rate, a higher systolic arterial pressure and end-systolic stress. Furthermore, they had an increased velocity of fiber shortening (P less than 0.01) and shorter left ventricular ejection time (P less than 0.001). In summary, present data suggest the possibility that parathormone may exert myocardial effects in hemodialysis patients.

Adult↗
PubMed1987

The role of aluminum in the development of hypercalcemia in the rat.

The present study evaluates the effect of an intravenous (i.v.) aluminum infusion on total and ionized calcium. Seven groups of rats were studied, and it was found that the magnitude of hypercalcemia was dose dependent. During a two hour i.v. infusion containing 0.4 mg aluminum per 100 grams of body weight, the total plasma calcium increased from 9.7 +/- 0.2 to 12.7 +/- 0.7 mg/dl (X +/- SE, P less than 0.02) while the ionized calcium decreased from 5.1 +/- 0.12 to 4.05 +/- 0.24 mg/dl (P less than 0.001). The increase in plasma calcium occurred in intact and parathyroidectomized rats, and the hypercalcemia could not be attributed to changes in PTH, arterial pH, plasma protein, or plasma phosphate. In vitro studies indicate that the addition of aluminum to rat plasma results in decreased ionized calcium concentration. Similarly, ultrafilterable calcium declined from 5.4 +/- 0.17 to 4.53 +/- 0.12 mg/dl (P less than 0.001) after the addition of aluminum to rat plasma. In summary, high levels of intravenous aluminum increase total plasma calcium and decrease ionized calcium. As also supported by in vitro data, the most probable mechanism is increased binding of calcium in the plasma which decreases ionized calcium. As a result of the decreased concentration of ionized calcium, movement of bone and interstitial calcium into the vascular space may occur, thus increasing total plasma calcium.

Aluminum↗
PubMed1987

Uremic cardiomyopathy: an inadequate left ventricular hypertrophy.

Echocardiographic study of the left ventricle was performed in 57 selected, normotensive hemodialysis patients in comparison to 40 healthy controls matched for sex, age and blood pressure. The statistically significant abnormalities in uremic patients were an enlargement of the left ventricular end-diastolic diameter (LVEDiD) (5.58 +/- 0.60 vs. 5.05 +/- 0.5 cm; P less than 0.001) and an increase in the left ventricular radius to posterior wall-thickness ratio (r/Th) (3.65 +/- 0.68 vs. 3.27 +/- 0.44; P less than 0.001). Enlargement of the ventricle was related to anemia (P less than 0.001) and the hemodynamic effect of arteriovenous fistula. Ventricular radius to wall thickness ratio was inversely related to systolic arterial pressure in controls (P less than 0.001) and patients (P less than 0.01) with a significant upward shift of the regression in dialysis patients (P less than 0.001). In dialysis patients, the left ventricular posterior wall thickness (LVPWT) was inversely correlated to serum parathormone (PTH) level (P less than 0.001), and r/Th ratio was positively correlated to serum PTH (P less than 0.001). Bone biopsy was performed in 28 patients. Histomorphometric indexes of osteitis fibrosa were in dialysis patients, correlated to echocardiographic abnormalities; osteoclasts number was inversely correlated to LVPWT (P less than 0.001) and positively related to r/Th ratio (P less than 0.001). Osteoclastic resorption surfaces and LVPWT were inversely correlated (P less than 0.001), while a positive correlation between r/Th ratio and osteoclastic resorption surfaces was observed (P less than 0.001). Osteoblastic surfaces and tetracycline double-labeled surfaces were also correlated to LVPWT (P less than 0.001) and r/Th ratio (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Protein synthesis, cellular amino acids, and energy levels in CAPD patients.

Cellular energy-related bioactivities [energy charge = ATP + 0.5 ADP/(ATP + ADP + AMP)], enzyme activities adenylate kinase, pyruvate kinase, phosphofructokinase, glucose-6-phosphate dehydrogenase, free amino acids in plasma and cells, and protein synthesis (3H-leucine incorporation) were measured in granulocytes isolated from peripheral blood of 13 CAPD-treated adult patients. The values were compared with 37 normal adult controls, 29 of whom had complete data for all biochemical parameters. Eleven of the CAPD patients were studied a second time, 3 to 8 months after the first study. Initially, after 20 +/- 8 months of CAPD compared (P less than 0.05, only) to controls, the patients had normal or increased activities of the enzymes pyruvate kinase, phosphofructokinase, glucose-6-phosphate dehydrogenase, in contrast to previous results from hemodialyzed patients; but adenylate kinase, ATP, and protein synthesis were reduced. Concentrations of many amino acids in plasma were abnormal, including reduced valine, leucine, threonine, tryptophan, and tyrosine, as noted by others. Histidine, glutamic acid, and citrulline especially were increased. The intracellular concentrations of the essential amino acids were within normal limits, but citrulline, glycine, and taurine levels were markedly increased while glutamic acid and SAGN (serine + asparagine + glutamine) were decreased. With the second study, intracellular energy-related bioactivities and the abnormal concentrations of the amino acids in plasma were essentially unchanged. However, virtually all the intracellular amino acid concentrations were higher. These results also were in striking contrast to previously reported hemodialysis patients in whom the intracellular concentrations of the branched-chain amino acids and methionine as well as protein synthesis were strikingly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Hypophosphatemia in long-term renal transplant recipients: effects on bone histology and 1,25-dihydroxycholecalciferol.

The effects of long-term hypophosphatemia were studied in 10 renal transplant recipients with persistent hypophosphatemia. The renal transplant recipients are 3-14 years (mean 8.7 +/- 4 years) post transplantation. The mean (+/- SD) serum calcium, phosphate, and creatinine levels are 9.66 +/- 0.42, 2.29 +/- 0.16, and 1.47 +/- 0.23 mg/dl, respectively. Carboxy (C)-terminal parathyroid hormone (PTH) is elevated in 8 hypophosphatemic renal transplant recipients. The mean 1,25-dihydroxycholecalciferol [1,25(OH)2D3] level is 33 +/- 20 pg/ml (normal 19-55 pg/ml) compared to 42 +/- 0.6 pg/ml (NS) in 4 normophosphatemic renal transplant recipients with comparable renal function. The 1,25(OH)2D3 level correlates with C-PTH (p less than 0.01) but not serum phosphate. Anterior iliac crest bone biopsies were obtained in all 10 hypophosphatemic renal transplant recipients. Histomorphometric analysis of osteoblastic osteoid, total surface osteoid, bone-osteoclast interface, total resorption, osteoclasts/mm2, osteoid seam width, and relative osteoid volume are not significantly different from normals. Trabecular bone volume is decreased (15.6 +/- 5.7 vs. 23 +/- 5%, p less than 0.01). Comparison of dynamic parameters with normal reveals no differences in appositional and bone formation rate. In summary, in hypophosphatemic renal transplant recipients: hypophosphatemia does not produce osteomalacia; hyperparathyroidism is often observed, and plasma 1,25(OH)2D3 levels, in general, remain in the normal range.

Adult↗