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Biomedical subjects

W G Goodman

Publications and source records attributed to W G Goodman.

At least 91 records · Page 5Linked to original sources
PubMed1991

Renal osteodystrophy in dialyzed children.

The histological and biochemical features of renal osteodystrophy are described in pediatric patients undergoing continuous peritoneal dialysis (CAPD/CCPD). Fifty-eight patients aged between 1.2 and 20 years have been evaluated. Secondary hyperparathyroidism was present in 70% of patients, despite treatment with oral calcitriol. Low bone formation was found in 16% and one half of those had overt osteomalacia with evidence of aluminum accumulation. Aplastic bone was present in 9% of the patients and in most of these patients there was not evidence of aluminum accumulation. The biochemical determinations were poor predictors of the different bone lesions. The skeletal response to oral calcitriol therapy was evaluated in 16 patients aged 12 +/- 6 years and treated with CAPD/CCPD. All patients have bone biopsy findings of secondary hyperparathyroidism at initial biopsy and follow-up bone biopsies performed 14 +/- 5 months demonstrated persistence of secondary hyperparathyroidism in most of the patients. Modified techniques for oral calcitriol administration and the potential value of intraperitoneal calcitriol may have a new role in the management of secondary hyperparathyroidism in patients with chronic renal failure.

Adolescent↗
PubMed1990

Homeostatic and developmental control of cell size and shape in an insect epithelium, the epidermis of Manduca sexta.

In contrast to previously described transformations of insect epidermal cells, morphological changes in the larval epidermis of Manduca sexta involve large changes in cell volume: a threefold increase at the beginning and a twofold decrease at the end of the last feeding phase. The volume changes are determined, in part, or entirely, by changes in cell height (cell elongation and cell shortening). Initial cell elongation occurs in a region-specific manner, whereas subsequent cell shortening affects all of the epidermis equally. As shown by ligation experiments and hormone treatments in tissue culture, larval changes in cell height, unlike cell elongation and differentiation in prepupae, are not regulated by developmental hormones (juvenile hormones, ecdysteroids). Instead, the maintenance of a normal columnar epithelium in fifth instars depends on continuous growth. Lack of food, especially protein, results in reversible cell shortening at any time during the feeding phase. Intake of water does not mitigate this cellular response; cell shortening is also insensitive to ouabain but inhibited by cold treatments. We propose that during larval growth epidermal cell height is under specific homeostatic control, independent of mechanisms regulating cell width, ploidy levels, or mitotic activity.

Animals↗
PubMed1990

Prospective evaluation of aluminum loading from formula in infants with uremia.

Assessment of potential aluminum loading from regular ingestion of a commercial infant formula (Similac PM 60/40), as the only milk substitute, was made in 14 infants aged 9.6 +/- 4.4 months who were also undergoing continuous cycling peritoneal dialysis. Tissue aluminum accumulation was assessed by serial measurements of plasma aluminum levels, from the increment in plasma aluminum after a standardized deferoxamine infusion, and from quantitative histomorphometry of bone and measurements of total bone aluminum content. Initial mean plasma aluminum levels were 0.61 +/- 0.32 mumol/L, (normal 0.30 +/- 0.04 mumol/L), and values were less than 0.92 mumol/L during the follow-up of 20 +/- 8 months. Plasma aluminum levels increased from 0.59 +/- 0.18 to 0.88 +/- 0.22 mumol/L after a single dose of deferoxamine. The histochemical stain for bone aluminum was negative for all patients, and the bone aluminum content was 0.27 +/- 0.22 mmol/kg dry weight (normal 0.08 +/- 0.04 mmol/kg dry weight). Thus the infant formula Similac PM 60/40 can be safely used in infants with chronic renal failure.

Aluminum↗
PubMed1990

Pharmacokinetics of calcitriol in continuous ambulatory and cycling peritoneal dialysis patients.

Oral calcitriol is commonly used for the treatment of secondary hyperparathyroidism in patients undergoing long-term dialysis, but it has been suggested that intravenous (IV) or intraperitoneal (IP) administration enhances the therapeutic efficacy of the sterol. To examine potential mechanisms for this difference, the bioavailability of calcitriol was evaluated after single oral (PO), IV, and IP doses of 60 ng/kg in each of six adolescent patients with osteitis fibrosa undergoing continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD). Serum calcitriol levels were 3.6 +/- 4.3, 8.2 +/- 7.5, and 2.5 +/- 3.0 pg/mL, respectively, before IV, PO, and IP doses of the sterol; these values increased to similar levels at 24 hours: 55.6 +/- 14.6 pg/mL after PO, 56.4 +/- 17.6 pg/mL after IV, and 53.8 +/- 20.1 pg/mL after IP. Serum calcitriol levels were higher 1, 3, and 6 hours after IV injections than after PO or IP doses; values thereafter did not differ among groups. The bioavailability of calcitriol, determined from the 24-hour area under the curve (AUC0-24) for the increase in serum calcitriol concentration above baseline values was 50% to 60% greater after IV, 2,340 +/- 523 pg.mL-1.h-1, than after PO, 1,442 +/- 467 pg.mL-1.h-1, or IP, 1,562 +/- 477 pg.mL-1.h1, dosages, P less than 0.05. These differences were due to higher values for AUC during the first 6 hours after calcitriol administration. Although IP calcitriol did not increase sterol bioavailability, radioisotope tracer studies indicated that 35% to 40% of the hormone adheres to plastic components of the peritoneal dialysate delivery system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Characterization of the transferrin receptor in UMR-106-01 osteoblast-like cells.

The accumulation of iron or aluminum can cause metabolic bone disease, but the mechanisms by which these agents affect bone metabolism remain uncertain. Since transferrin (Tf) can bind several different metals in plasma, equilibrium radioligand binding studies were performed to identify and characterize the Tf receptor in UMR-106-01 osteoblast-like cells; the role of Tf as a modifier of metal-induced changes in cell proliferation was also examined. Osteoblast-like cells grown in serum-free medium have approximately 40,000 Tf receptors on the cell membrane. Tf receptor expression increases during iron depletion and decreases with iron supplementation; the number of Tf receptors was also inversely related to both cell density and the rate of cell proliferation in vitro. Physiological levels of unsaturated Tf (5 microM) enhanced DNA synthesis in osteoblast-like cells maintained in serum-free medium, as measured by the incorporation of tritiated thymidine into DNA. Although neither 10 microM iron (Fe) nor 10 microM gallium (Ga), a known antiproliferative agent, altered DNA synthesis in UMR-106-01 cells during 48-h incubations in serum-free medium, both agents reduced the rate of DNA synthesis when added to serum-free medium containing 5 microM apo-Tf. Decreases in the incorporation of [3H] thymidine into DNA were also noted in osteoblast-like cells incubated for 48 h with 3 microM partially saturated iron Tf or gallium Tf. The results indicate that osteoblast-like cells have a single class of membrane receptors for Tf and that the regulation of Tf receptor expression in UMR-106-01 cells is similar to that in other cell types. The uptake of iron and gallium via the Tf-receptor complex can affect osteoblast proliferation, and such a mechanism may contribute to the bone cell toxicity of various metals.

Acetates↗
PubMed1990

A simplified method for synthesizing juvenile hormone-protein conjugates.

A convenient and simple method is presented for the synthesis of juvenile hormone-thyroglobulin conjugates. Methods previously described for this hapten linkage have used a two-step process in which a reactive intermediate was isolated and then used for conjugation. With the approach described here, an efficient, single-step conjugation reaction is effected between the carboxyl moiety of juvenile hormone III and the carrier protein, bovine thyroglobulin. Isolation of the reactive intermediate is eliminated. Isotopic dilution indicates that between 100 and 115 moles of hapten are conjugated per mole of carrier protein.

Carrier Proteins↗
PubMed1988

Glucose transport in osteoblast-enriched bone explants: characterization and insulin regulation.

Insulin has potent effects on osteoblast function both in vivo and in vitro. In various insulin-sensitive tissues, stimulation of glucose transport and metabolism are hallmarks of insulin action, and have been postulated to play a role in insulin regulation of cellular function. However, insulin effects on glucose metabolism in osteoblast-like cells have not been demonstrated. Therefore we examined the in vitro effects of insulin on hexose uptake in an osteoblast-enriched rat bone explant preparation. Uniform 5-mm-diameter punch sections were obtained from the cartilage-free frontal portions of the calvaria of 3-day-old rats, and the periosteum was removed. The resulting sections contained a highly enriched population of osteoblast-like cells as determined by histologic criteria, elimination of calcitonin-stimulatable cAMP generation, and enhancement of PTH-stimulatable cAMP generation per microgram of DNA. Sections were incubated for 24 hr at 37 degrees C in BGJb medium and then transferred to modified glucose-free Krebs-Ringer bicarbonate buffer for 2-deoxy-D-glucose (2-DG) uptake studies. 3H-2-DG uptake was linear with time over 60 min, temperature sensitive, and inhibited by 5 mM phloridzin. Kinetic analysis of 2-DG uptake at 25 degrees C demonstrated a saturable transport mechanism with a Km of 2.2 mM, similar to that observed for 2-DG transport in other tissues. Studies of competitive inhibition by other sugars demonstrated a transport specificity for 2-DG that was comparable to that previously observed in fat and muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1988

Renal osteodystrophy: some new questions on an old disorder.

The two major lesions of renal osteodystrophy are osteitis fibrosa cystica (OFC) and osteomalacia (OM). OFC is the characteristic bone lesion of uremic hyperparathyroidism. Although renal failure causes predictable parathyroid hyperplasia, the precise pathogenetic mechanism is still not defined. The "hyperphosphatemia-hypocalcemia-parathyroid hormone (PTH) hypersecretion" sequence of events is no longer an adequate model for the pathogenesis of uremic hyperparathyroidism. Other abnormalities associated with uremia include reduced 1,25-dihydroxyvitamin D (1,25D) synthesis, changes in intracellular phosphorus content or transcellular phosphate fluxes, or alteration in PTH metabolism, eg, change in set-point for PTH secretion. Each abnormality interacts with others and contributes to PTH hypersecretion, but none can completely account for the development and persistence of hyperparathyroidism in renal failure. The possibility that uremia may directly cause parathyroid hyperplasia remains open. It is also possible that factor(s) that initiate hyperparathyroidism may turn out to be quite different from that which sustains the hyperparathyroid state. Although both vitamin D-deficient and vitamin D-resistant OM may develop in patients with renal failure, the majority of uremic OM seen currently is "vitamin D-refractory." Although now there is persuasive evidence implicating aluminum (Al) accumulation as the major pathogenetic cause for the mineralization defect seen in this disorder, additional disturbances may play important contributory roles. Such factors would include extraskeletal effects of Al, differences in host-susceptibility to this element, the localization of Al within bone, uremia per se, and the participation of other metals and toxins. Finally, possible interactions between hyperparathyroidism and OM of uremia are speculated on.

Aluminum↗
PubMed1988

Bone disease in pediatric patients undergoing dialysis with CAPD or CCPD.

The histologic features of renal osteodystrophy and the prevalence of bone aluminum deposition in children receiving regular dialysis have not been described. Forty-four pediatric patients undergoing continuous ambulatory (CAPD) or cycling (CCPD) peritoneal dialysis had bone biopsies and deferoxamine (DFO) infusion tests; all were receiving oral calcitriol. Osteitis fibrosa (OF) was found in 39%, mild lesions (M) in 25%, normal histology (NH) in 16%, aplastic lesions (AP) in 11%, and osteomalacia (OM) in 9%. Bone surface aluminum (SA) was present by histochemical staining in 10 out of 20 given aluminum-containing phosphate-binding agents and in 0 of 24 treated with calcium carbonate; chi 2 = 15.5, P less than 0.0001. Serum biochemistries and DFO infusion tests failed to predict bone histology, but plasma aluminum levels were markedly elevated and bone aluminum content was highest in patients with OM. Bone formation rate (BFR) correlated with serum parathyroid hormone (PTH), r = 0.55, P less than 0.001; BFR was inversely related to bone aluminum content (r = -0.42, P less than 0.01), even in patients with OF (r = -0.66, P less than 0.05). All patients with SA greater than 30% had normal or reduced BFR when compared to those with SA less than 30%; chi 2 = 12.2, P less than 0.005. Based on SA greater than 30%, six patients were classified as aluminum-related bone disease: three OM, one AP, and two NH. Two-thirds of pediatric patients undergoing CAPD/CCPD have persistent hyperparathyroidism despite treatment with calcitriol, but aluminum can adversely affect BFR when SA exceeds 30% regardless of histologic lesion or serum PTH level.

Aluminum↗
PubMed1987

Radiographic manifestations of experimental aluminum toxicity in growing bone.

To evaluate the effect of aluminum on growing bone in the presence of normal renal function, the following experiment was performed. Eight littermate pair-fed pigs (5 weeks old) were randomly assigned to one of two study groups: control C, n = 4, or aluminum treated Al, n = 4. Daily intravenous injections of either aluminum 1.5 mg/kg/day (Al group) or vehicle only (C group) were given during the 8-week duration of the study. The radiographic findings which appeared in the aluminum-treated group and not in the controls consisted of areas of sclerosis in the submetaphyseal regions and the periphery of epiphyses. In addition there was separation of the anterior tibial tubercle. The growth plates did not increase in width despite the presence of osteomalacia and histologic evidence of extensive deposition of aluminum in bone. The area of sclerosis visualized in the radiographs correlated histologically with thickened bony trabeculae. The increased width of these trabeculae is attributable to an increase in primary spongiosum and broadened seams of osteoid.

Aluminum↗
PubMed1987

Effects of a magnesium-free dialysate on magnesium metabolism during continuous ambulatory peritoneal dialysis.

While the use of magnesium-containing compounds is usually contraindicated in dialysis patients, the risk of toxicity from hypermagnesemia can be reduced by lowering the magnesium concentration in dialysate. We examined the effects of a magnesium-free dialysate on both serum magnesium level and the peritoneal removal rate of magnesium over 12 weeks in 25 stable patients undergoing continuous ambulatory peritoneal dialysis (CAPD). After 2 weeks, the serum magnesium level decreased from 2.2 to 1.9 mg/dL (0.9 to 0.8 mmol/L) (P less than .02) and the peritoneal removal rate increased from 66 to 83 mg/d (2.8 to 3.5 mmol/d) (P less than .05), with both values remaining stable thereafter. There was a strong association between these parameters (r = -0.62, P less than .05), suggesting that the serum magnesium level decreased as a result of the initial increased peritoneal removal rate. For an additional 4-week period, a subgroup of nine patients received magnesium-containing, phosphate binding agents instead of those containing only aluminum. During this phase, serum inorganic phosphorus was well controlled. The serum magnesium level increased only from 1.8 to 2.5 mg/dL (0.7 to 1.0 mmol/L) (P less than .05), due in great part to the concomitant 41% rise in peritoneal magnesium removal from 91 to 128 mg/d (3.8 to 5.3 mmol/d) (P less than .05). No toxicity was noted during the entire 16-week study period, nor did serum calcium change. Thus, serum magnesium levels remained within an acceptable range as magnesium-containing phosphate binders were given through the use of magnesium-free peritoneal dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum Hydroxide↗
PubMed1987

"High-dose" calcitriol for control of renal osteodystrophy in children on CAPD.

High doses of calcitriol were used prospectively for 11 to 29 months to raise serum calcium levels in an effort to control renal osteodystrophy in 16 children undergoing CAPD. Serum Ca, P, iPTH and alkaline phosphatase were measured monthly; hand radiographs were obtained every six months, and a semiquantitative score of bone abnormalities was evaluated by two independent observers. During the study, serum Ca increased from 9.9 +/- 0.9 to 11.0 +/- 0.6 mg/dl (P less than 0.001); serum iPTH decreased by 113 +/- 131 microliter Eq/ml (P less than 0.005); serum P was unchanged; and serum alkaline phosphatase fell by 33 +/- 46% (P less than 0.02), 530 +/- 397 to 204 +/- 551 IU/liter. The radiographic score fell from 4.8 +/- 4.6 to 0.9 +/- 1.2 (P less than 0.005). The average and maximal doses of calcitriol were 0.61 +/- 0.37 and 0.95 +/- 0.56 microgram/day or 28 +/- 18 and 46 +/- 28 ng/kg body wt/day, respectively. Transient and asymptomatic hypercalcemia occurred in nine patients and two patients had reversible conjunctivitis in association with the hypercalcemia. Thus, "high dose" calcitriol prevented or controlled progression of hyperparathyroid bone disease in most pediatric CAPD patients. The failure to suppress PTH or reverse secondary hyperparathyroidism until the serum Ca rose to 10.5 to 11.0 mg/dl could reflect an increase in the "set point" for PTH suppression by serum calcium in many uremic children.

Adolescent↗
PubMed1987

Thyroparathyroidectomy modifies the skeletal response to aluminum loading in the rat.

Diminished parathyroid hormone (PTH) secretion may contribute to the accumulation of aluminum (Al) in bone and to impaired bone formation in Al-related bone disease. Therefore, intact (AL, N = 9) and thyroparathyroidectomized (TPTX-AL, N = 9) rats were given intraperitoneal injections of Al, 2 mg/day, for 42 days; intact control (C, N = 11) and TPTX control (TPTX-C, N = 9) animals received i.p. injections of vehicle only. Quantitative bone histology and measurements of mineralized bone formation (Rbf) using double tetracycline labeling were done for cortical and for trabecular bone; trabecular bone aluminum content (BA) was determined by histochemical methods. BA did not differ between AL and TPTX-AL, 33 +/- 13% versus 39 +/- 14%, and Rbf decreased similarly from control values in both Al-treated groups. In contrast, osteoid production was impaired to a greater extent in TPTX-AL than in AL. Thus, osteoid area and osteoid seam width were each lower in TPTX-AL than in TPTX-C; these values did not differ between AL and C. TPTX can aggravate Al induced reductions in osteoid synthesis, and low serum PTH levels may contribute to the pathogenesis of aplastic bone. However, reductions in Rbf during Al loading are not mediated by PTH.

Aluminum↗
PubMed1987

Tissue and cellular basis for impaired bone formation in aluminum-related osteomalacia in the pig.

Bone formation is impaired in aluminum-associated bone disease. Reductions in the number of osteoblasts or in the function of individual osteoblasts could account for this finding. Thus, quantitative bone histology and measurements of bone formation were done at three skeletal sites in piglets given aluminum (Al) parenterally, 1.5 mg/kg per d, for 8 wk (Al, n = 4) and in control animals (C, n = 4). Bone Al was 241 +/- 40 mg/kg per dry weight in Al and 1.6 +/- 0.9 in C, P less than 0.001. All Al-treated animals developed osteomalacia with increases in osteoid seam width, osteoid volume, and mineralization lag time at each skeletal site, P less than 0.05 vs. C for all values. Mineralized bone formation at the tissue level was lower in Al than in C, P less than 0.05 for each skeletal site, due to reductions in active bone forming surface. Bone formation at the cellular level was similar in each group, however, and total osteoid production by osteoblasts did not differ in C and Al. Aluminum impairs the formation of mineralized bone in vivo by decreasing the number of active osteoblasts, and this change can be distinguished from the effect of aluminum to inhibit, either directly or indirectly, the calcification of osteoid.

Aluminum↗