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Biomedical subjects

W G Goodman

Publications and source records attributed to W G Goodman.

At least 73 records · Page 4Linked to original sources
PubMed1993

Comparison of two juvenile hormone radioimmunoassays.

Juvenile hormone from the hemolymph of adult worker honey bees of known age and behavioral status was extracted and analyzed by two different radioimmunoassays in two independent laboratories. The assays are different in hapten attachment, radiolabeled tracer, and the method by which bound and unbound hormone are separated. Despite these differences in the methods, hormone determinations were in excellent agreement at lower levels (0-50 ng/ml) but diverged as the hormone concentrations increased (> 50 ng/ml). The relative changes are in good agreement, with a correlation coefficient of 0.97.

Animals↗
PubMed1993

Analysis and modification of thiols in the hemolymph juvenile hormone binding protein of Manduca sexta.

Hemolymph-induced in vitro modifications of the hemolymph juvenile hormone binding protein from the tobacco hornworm, Manduca sexta, were analyzed by polyacrylamide gel electrophoresis, Western blots, and equilibrium dialysis. Upon hemolymph melanization, a complex reaction involving polymerization of phenolic compounds, multiple forms of the protein were detected. Under melanizing conditions, one slower- and several faster-migrating proteins were observed. When the hemolymph was treated with 100 mM catechol, a melanin precursor, two well-defined forms of the binding protein appeared. When the protein was incubated with excess catechol (> 100 mM) a single faster-migrating form appeared. Both fast and slow forms bound juvenile hormone I with similar efficiency. These results were duplicated using the thiol modifying reagents p-chloromercurobenzoate and N-ethylmaleimide, suggesting modification of cysteine residues. Using differential alkylation, it was determined that hemolymph juvenile hormone binding protein contained two cystine and two cysteine residues. One of the cysteines is exposed and readily accessible for modification. Since modification of the exposed free thiol did not alter binding, it presumably resides outside the hormone-binding domain. The analyses support the observation that there is a single form of the hemolymph juvenile hormone-binding protein in our strain of M. sexta.

Alkylation↗
PubMed1993

Disodium ethylenediaminetetraacetate: adverse effects in dialyzed children.

The present report describes untoward effects of disodium ethylenediaminetetraacetate (EDTA) in three of six pediatric patients treated with continuous cycling peritoneal dialysis, in whom this agent was infused intravenously to lower serum ionized calcium levels during dynamic testing of parathyroid gland function. Patients developed an influenza-like syndrome characterized by fever rhinorrhea, cough, sneezing, and lacrimation. All symptoms disappeared within 24 h. A similar degree of hypocalcemia was induced with sodium citrate, an alternative hypocalcemic agent, in the same patients without side effects. Sodium citrate, rather than EDTA, should be used to induce hypocalcemia when assessing parathyroid gland dynamics in children with end-stage renal disease.

Adolescent↗
PubMed1993

Aplastic osteodystrophy without aluminum: the role of "suppressed" parathyroid function.

We evaluated 259 dialysis patients using serum parathyroid hormone (PTH, IRMA; normal range 1 to 5.5 pM or 10 to 55 pg/ml), the deferoxamine infusion test and iliac crest bone biopsy to determine the various forms of renal osteodystrophy and their risk factors. Although half of the biopsied patients had low turnover osteodystrophy, evidence of aluminum toxicity was present in only 1/3 of them. Additional risk factors for this bone lesion included treatment with peritoneal dialysis, ingestion of calcium carbonate, diabetes mellitus and advanced age. The PTH levels in patients with the aplastic lesion were significantly lower than in patients with normal or high bone turnover lesions [7.7 +/- 6.1 vs. 36.9 +/- 3.2 pM (77 +/- 61 vs. 369 +/- 32 pg/ml), P < 0.0001]. Aside from hypercalcemia, these patients were relatively asymptomatic. In a second study, 10 patients on peritoneal dialysis with the aplastic lesion had their dialysate calcium lowered from 1.62 to 1.0 mM. This resulted in a significant increase in PTH levels, from [3.7 +/- 0.8 to 10.6 +/- 1.9 pM (37 +/- 8 to 106 +/- 19 pg/ml), P < 0.001] which persisted over the nine-month observation period. In conclusion, the aplastic lesion is the most common form of renal osteodystrophy, with aluminum intoxication implicated in only 1/3 of the cases. In the remainder, factors identified include therapy with peritoneal dialysis using supraphysiological dialysate calcium, oral CaCO3 intake and diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1993

Recent advances in the management of renal osteodystrophy in children.

Secondary hyperparathyroidism remains the predominant histologic lesion in pediatric patients undergoing regular dialysis, but recent evidence indicates that the regulation of parathyroid hormone secretion by calcium does not differ substantially between patients with osteitis fibrosa and subjects with normal renal function. Growth retardation and skeletal deformities are major findings in pediatric patients with renal osteodystrophy, and alterations in vitamin D metabolism and insulin-like growth factor almost certainly contribute to these findings. Avoidance of aluminum-containing medications and the introduction of intermittent calcitriol therapy provide newer approaches to the effective management of secondary hyperparathyroidism in pediatric patients with end-stage renal disease.

Child↗
PubMed1993

Direct in vivo comparison of calcium-regulated parathyroid hormone secretion in normal volunteers and patients with secondary hyperparathyroidism.

The regulation of PTH secretion by calcium is altered in patients with primary hyperparathyroidism. A similar disturbance may occur in secondary hyperparathyroidism, but direct in vivo comparisons of PTH secretion in normal subjects and those with secondary hyperparathyroidism have not been made. Thus, 13 patients with end-stage renal failure and secondary hyperparathyroidism and 20 healthy volunteers underwent dynamic tests of PTH secretion. Changes in ionized calcium were induced by 2-h iv infusions of calcium gluconate or sodium citrate on consecutive days, and the sigmoidal relationship between serum ionized calcium and PTH levels was examined. During sodium citrate infusions, serum ionized calcium levels decreased by 0.21 +/- 0.04 and 0.20 +/- 0.05 mmol/L, respectively (mean +/- SD), in normal volunteers and dialyzed patients (P = NS). Serum PTH levels rose from 27 +/- 7 to 107 +/- 33 pg/mL in controls and from 480 +/- 238 to 859 +/- 412 pg/mL in dialyzed subjects; thus, maximum PTH levels were 396% of preinfusion values in normal subjects, but only 79% greater than baseline values in dialyzed patients (P < 0.001). During the first 30 min of calcium infusions, the increase in serum ionized calcium did not differ between groups, but PTH levels fell more rapidly in normal volunteers; values were 24% of preinfusion levels in controls, but only 56% of the baseline in dialyzed patients (P < 0.01) after 30 min. Minimum PTH levels were attained after 50 min of calcium infusion in normal volunteers and after 70 min in dialyzed patients. The derived values for set-point were 1.21 +/- 0.04 and 1.24 +/- 0.06 mmol/L, respectively, in control and dialyzed subjects (P = NS). These results do not support the contention that the set-point for calcium-regulated PTH secretion is greater than normal in patients with secondary hyperparathyroidism due to end-stage renal disease.

Adolescent↗
PubMed1993

Bone metabolic activity measured with positron emission tomography and [18F]fluoride ion in renal osteodystrophy: correlation with bone histomorphometry.

We evaluated the bone metabolic activity in patients with renal osteodystrophy using positron emission tomography and [18F]fluoride ion. Eight patients had secondary hyperparathyroidism (HPT), and three had low-turnover bone disease. Eleven normal subjects were also studied, and three of the eight HPT patients were reevaluated after therapy. A rate constant (K) describing the net transport of [18F] fluoride ion into a bound compartment in bone was calculated using both a three-compartment model and Patlak graphical analysis. Values of K were compared with biochemical data and with histomorphometric indices. The results indicate that K is significantly higher (P < 0.01) in HPT patients than in normal subjects and patients with low-turnover bone disease. Values of K correlated with serum alkaline phosphatase (r = 0.81) and PTH (r = 0.93) levels and with histomorphometric indices of bone formation rate (r = 0.84, P < 0.01) and eroded perimeter (r = 0.77, P < 0.05). Values of K decreased by 40 and 30%, respectively, in two patients who underwent parathyroidectomy and medical therapy. Positron emission tomography studies of bone using [18F]fluoride ion can differentiate low turnover from high turnover lesions of renal osteodystrophy and provide quantitative estimates of bone cell activity that correlate with histomorphometric data.

Adolescent↗
PubMed1992

The use of 1,25-dihydroxyvitamin D3 in early renal failure.

Alterations in renal calcitriol synthesis are important in the pathogenesis of secondary hyperparathyroidism in patients with progressive renal failure. Many of the manifestations of secondary hyperparathyroidism can be reversed by treatment with 1 alpha-hydroxylated vitamin D sterols, such as calcitriol and 1 alpha-hydroxyvitamin D3, but some studies suggest that such treatment accelerates the rate of progression of renal disease in patients with mild to moderate renal failure. Thus, calcitriol and 1 alpha-hydroxyvitamin D3 have been used infrequently in this group of patients. A review of more than 20 clinical reports indicates that the use of calcitriol or 1 alpha-hydroxyvitamin D3, in daily doses of 0.25-0.5 microgram, is rarely associated with hypercalcemia, hyperphosphatemia, or impairment in renal function. If such complications arise, they are usually reversible when treatment with vitamin D sterols is withdrawn and serum calcium levels return to pretreatment values. There is evidence that calcitriol impairs creatinine secretion by the renal tubule; thus, serum creatinine levels may increase and measurements of creatinine clearance may fall during calcitriol therapy in patients with mild to moderate renal failure without any change in true glomerular filtration rate. Daily oral doses of 0.25-0.50 microgram of calcitriol or 1 alpha-hydroxyvitamin D3 are well tolerated, and they can reverse the biochemical and histologic features of secondary hyperparathyroidism. Calcitriol therapy may be particularly valuable in patients recognized to be at higher risk of developing progressive secondary hyperparathyroidism as their renal failure slowly advances.

Administration, Oral↗
PubMed1991

Changes in vertebral bone density in black girls and white girls during childhood and puberty.

BACKGROUND: The prevalence of osteoporosis and the incidence of vertebral fractures are lower in black women than in white women, findings generally attributed to racial differences in adult bone mass. Little is known, however, about the factors that contribute to racial variations in bone mass or the time of life when such differences become manifest. This study was done to characterize the changes in vertebral bone density at various stages of sexual development in black and white females. METHODS: We measured cancellous vertebral bone density by quantitative computed tomography in 75 black female subjects between 2 and 20 years old and 75 whites matched for age and stage of sexual development. RESULTS: The vertebral bone density did not differ between black girls and white girls before puberty. Bone density increased during puberty in each racial group, but the magnitude of the increase from prepubertal values was substantially greater in black than in white subjects (34 percent vs. 11 percent). CONCLUSIONS: The marked difference between black and white females in cancellous vertebral bone density occurs during a relatively brief period late in puberty. Metabolic and hormonal events related to the achievement of sexual maturity during adolescence may be important determinants of racial differences in bone mass in women.

Adolescent↗
PubMed1991

Aluminum accumulation during treatment with aluminum hydroxide and dialysis in children and young adults with chronic renal disease.

BACKGROUND: The control of hyperphosphatemia is a major clinical problem in patients with chronic renal failure receiving regular dialysis treatment. Despite continuing concern about aluminum toxicity, aluminum-containing antacids are still used in many of these patients as phosphate-binding agents. Although maximal acceptable doses of aluminum hydroxide have been recommended, the safety and efficacy of these guidelines have not been evaluated. METHODS: Seventeen children and young adults (mean [+/- SD] age, 14.1 +/- 3.7 years) undergoing regular peritoneal dialysis were randomly assigned to treatment with either aluminum hydroxide (n = 7; maximal dose, 30 mg per kilogram of body weight per day) or calcium carbonate (n = 10; dose range, 2.5 to 12 g per day, according to serum phosphorus levels). Aluminum retention was assessed by serial measurements of plasma aluminum, deferoxamine-infusion tests, and measurements of bone aluminum content during a mean (+/- SD) follow-up of 13 +/- 2 months. The evolution of bone disease was also evaluated. RESULTS: Plasma aluminum levels and the increment in plasma aluminum after infusion of deferoxamine increased from base-line values in the patients treated with aluminum hydroxide, and aluminum-related bone disease developed in one patient. Serum phosphorus levels remained higher and serum calcium levels lower in the patients receiving aluminum hydroxide than in those receiving calcium carbonate. The skeletal lesions of secondary hyperparathyroidism improved in 7 of 10 patients receiving calcium carbonate but persisted or progressed in 6 of 7 patients given aluminum hydroxide (P less than 0.025). CONCLUSIONS: Aluminum hydroxide is less effective than calcium carbonate as a phosphate-binding agent for the control of hyperphosphatemia and is associated with aluminum retention in children and young adults with chronic renal failure who are receiving dialysis therapy.

Adolescent↗
PubMed1991

Calcium citrate markedly enhances aluminum absorption from aluminum hydroxide.

The effect of calcium citrate on intestinal aluminum absorption, assessed by the increment in urinary aluminum excretion, was evaluated in eight normal men. Baseline urinary aluminum excretion was determined for 2 days; thereafter, subjects ingested aluminum hydroxide for 3 days. In a cross-over study, subjects were given either calcium citrate, 950 mg four times a day, or placebo during the 3 days of aluminum hydroxide ingestion (2.4 g/d). Plasma aluminum levels were measured on the second control day and the third day of aluminum hydroxide ingestion. Baseline urinary aluminum excretion was 0.02 +/- 0.004 (6.5 +/- 1.1 micrograms/g creatinine) and 0.03 +/- 0.005 mumol/mmol creatinine (7.4 +/- 1.3 micrograms/g creatinine). These values increased during aluminum hydroxide therapy, but values were much greater when calcium citrate was ingested with aluminum hydroxide. On 3 consecutive days, urinary aluminum excretion levels were 11.1 +/- 3.23, 8.8 +/- 2.9, and 5.3 +/- 0.7 times greater during the administration of calcium citrate with aluminum hydroxide than with aluminum hydroxide alone. Plasma aluminum levels did not differ in the two treatment groups. Thus, calcium citrate markedly enhances the absorption of aluminum from aluminum hydroxide and the two must not be prescribed together in patients with renal failure.

Adult↗
PubMed1991

Aluminum alters calcium influx and efflux from bone in vitro.

Aluminum retention can cause osteomalacia and adynamic lesions of bone in patients undergoing long-term dialysis. It is not known, however, whether aluminum inhibits the mineralization of bone directly or whether alterations in osteoblastic function mediate this response. To examine this issue, the uptake of 45Ca by 14-day embryonic chick calvaria was measured in vitro. Comparative studies were done in living and devitalized tissues to evaluate the role of bone cells in aluminum-related changes in 45Ca uptake. Aluminum was added to serum-free media as the citrate complex, and paired hemicalvaria maintained in equimolar sodium citrate served as controls. Aluminum citrate decreased the uptake of 45Ca into bone during 24 hour incubations to 76 +/- 3% and 38 +/- 2% (x +/- SD) of control values at 10 microM and 100 microM aluminum, respectively. No change in 45Ca uptake was observed at the end of four hour incubations with 100 microM aluminum citrate, whereas 45Ca uptake decreased from 356 +/- 48 to 266 +/- 36 cpm/micrograms bone, P less than 0.05, at eight hours and from 327 +/- 22 to 269 +/- 41 cpm/micrograms bone, P less than 0.05, at 24 hours. The inhibitory effects of 10 microM and 100 microM aluminum on 45Ca uptake were eliminated, however, in devitalized tissues, and reductions in 45Ca uptake during incubations with aluminum were markedly attenuated by lowering the media phosphorus level from 4.0 mM to 2.0 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1991

Effect of dietary calcium on bone density in growing rabbits.

Reductions in peak bone mass at skeletal maturity may increase the risk for the subsequent development of osteoporosis. Although changes in calcium intake can modify the rate of decline in bone density in the mature skeleton, longitudinal assessments of the effect of dietary calcium supplementation during skeletal growth on peak bone mass have not been done in humans or experimental animals. Thus quantitative computed tomography (QCT) was used to monitor changes in vertebral bone density at 6-wk intervals during growth from 8 wk of age until skeletal maturity at 35 wk in male New Zealand White rabbits maintained on diets containing 0.15% (low Ca), 0.45% (normal Ca), or 1.35% (high Ca) calcium. Serum parathyroid hormone (PTH) and calcitriol levels increased, and renal calcium excretion decreased in low Ca compared with normal Ca; in contrast, serum calcitriol levels decreased and renal calcium excretion increased from control values in high Ca. Vertebral bone density by QCT did not differ during growth between high Ca and normal Ca, and peak values at epiphyseal closure also did not differ in these two groups. Vertebral bone density was lower, however, throughout the study in low Ca, and peak values at epiphyseal closure remained below those in either normal Ca or high Ca. Quantitative bone histology revealed decreases in cortical thickness in the third lumbar vertebra in low Ca, whereas trabecular bone area did not differ among groups; there was no histological evidence of osteomalacia in low Ca. Thus dietary calcium restriction during growth reduces peak bone mass at skeletal maturity, but raising dietary calcium intake above normal levels does not increase peak bone mass in this experimental model.

Animals↗
PubMed1991

Transferrin enhances the antiproliferative effect of aluminum on osteoblast-like cells.

Aluminum (Al) retention in the body can cause metabolic bone disease. This disorder is characterized by reductions in the number of osteoblasts, a feature that suggests a disturbance in bone cell proliferation or differentiation. Because Al as well as iron (Fe) can bind to transferrin (TF) in plasma, the role of TF as a modifier of osteoblast proliferation was examined in UMR-106-01 osteoblast-like cells by measuring the incorporation of tritiated thymidine ([3H]-TdR) into DNA (counts.min-1.microgram cell protein-1, means +/- SE) during 48-h incubations in serum-free medium (SFM). In the absence of TF, DNA synthesis decreased when media levels of Al exceeded 6-10 microM. The mitogenic response to physiological levels of unsaturated TF (apo-TF) was attenuated however during incubations with TF that was partially saturated with Al (Al-TF). A similar inhibitory response was seen in cells incubated with the antiproliferative agent gallium (Ga) when added to SFM as partially saturated Ga-TF. TF produced a shift to the left in the inhibitory dose-response curve to Al in osteoblast-like cells; thus, DNA synthesis decreased at substantially lower media concentrations of Al in cells grown in SFM containing partially saturated Al-TF. The results indicate that TF is an important determinant of the inhibitory effect of Al on DNA synthesis by osteoblast-like cells at the micromolar levels of Al that can occur in plasma in vivo.

Aluminum↗
PubMed1991

Evolution of secondary hyperparathyroidism during oral calcitriol therapy in pediatric renal osteodystrophy.

The course of renal bone disease in children undergoing regular peritoneal dialysis has not been fully evaluated. In particular, only limited data are available regarding the therapeutic efficacy of oral calcitriol in this group of patients. Thus, bone biopsies were done before and after 12 months of treatment with daily doses of oral calcitriol in 33 pediatric patients undergoing CAPD or CCPD. In 10/13 patients with initial biopsy findings of osteitis fibrosa, skeletal lesions either failed to improve or worsened after 12 months of treatment; in contrast, 4/6 patients with mild lesions of secondary hyperparathyroidism demonstrated histologic improvement. Serum PTH levels, determined using a mid-region assay, were higher in patients who failed to improve during oral calcitriol therapy, and values increased progressively in this group. Serum PTH levels were unchanged in those who improved. These data indicate that secondary hyperparathyroidism remains a substantial clinical problem in pediatric patients receiving regular peritoneal dialysis; treatment with daily doses of oral calcitriol is only partially effective for the control of this disorder. Further assessment of alternatives to daily oral calcitriol administration such as pulse oral or intermittent intraperitoneal calcitriol therapy is warranted in order to provide more effective approaches to the management of secondary hyperparathyroidism in pediatric dialysis patients.

Administration, Oral↗
PubMed1991

Renal bone disease in pediatric patients receiving treatment with maintenance peritoneal dialysis.

The present review summarizes the characteristics of renal bone disease in pediatric patients treated with maintenance peritoneal dialysis. Fifty-eight patients underwent iliac crest bone biopsy after double tetracycline labeling, measurements of aluminum in bone and various serum biochemical determinations including serum PTH, alkaline phosphatase, calcium, phosphorus and aluminum. Evidence of osteitis fibrosa was present in 45% of patients and mild lesions of secondary hyperparathyroidism were found in an additional 25%. Thus, secondary hyperparathyroidism remains the predominant bone lesion despite the use of oral calcitriol. Evidence of aluminum accumulation was substantially less prevalent, findings not surprising due to the widespread use of calcium carbonate as the main phosphate binder agent. However, aplastic bone lesion without aluminum staining was present in the majority of patients with low-turnover lesions of the bone without osteomalacic findings. The long-term evolution of such lesions remains to be evaluated. The potential value of alternative modes of calcitriol administration for the control of secondary hyperparathyroidism is discussed as well as the differences in the bioavailability of sterol according to the different routes for calcitriol administration.

Aluminum↗
PubMed1991

Aluminum: effects on bone and role in the pathogenesis of renal osteodystrophy.

Renal osteodystrophy is a complex disorder that can produce a variety of histologic changes in bone. Classically, excess parathyroid hormone (PTH) secretion in patients with chronic renal failure leads to the development of skeletal lesions characterized by increases in bone cell activity and by high rates of bone formation and turnover. In contrast, aluminium retention in the body in those undergoing long-term dialysis is often associated with diminished bone cell activity and bone formation. In some patients with renal osteodystrophy, both pathogenic factors may be operative. Thus the histologic features in an individual patient can represent the combined manifestations of both excess PTH secretion and bone aluminum toxicity; the relative roles of each of these two pathogenic processes must be carefully evaluated. In the current review, several pathophysiologic mechanisms of aluminum toxicity in bone are summarized.

Aluminum↗