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J W Coburn

Publications and source records attributed to J W Coburn.

At least 19 recordsLinked to original sources
PubMed1996

1 alpha-Hydroxy-vitamin D2: a new look at an 'old' compound.

Calcitriol is effective in suppressing PTH levels in haemodialysis patients with hyperparathyroidism but has a low therapeutic index. There is a search for other vitamin D sterols that suppress PTH but cause less hypercalcaemia. We review evidence that 1 alpha-hydroxy-vitamin D2 (1 alpha-D2) may be an effective and safer alternative to calcitriol. In vitamin D-deficient rats, 1 alpha-D2 is equipotent to 1 alpha-D3, which is converted to calcitriol before it acts; but, in normal rats, 1 alpha-D2 is much less toxic at high doses. In osteopenia models, either steroid-induced or following ovariectomy, 1 alpha-D2 is equal to or more effective than 1 alpha-D3 in preventing bone loss but causes less hypercalciuria. Studies in osteoporotic women reveal minimal hypercalciuria with 1 alpha-D2 at doses up to 4 micrograms/day, data suggesting greater safety than reported with calcitriol or 1 alpha-D3. Preliminary data in haemodialysis patients with secondary hyperparathyroidism demonstrate the efficacy of 1 alpha-D2 in suppressing PTH levels with minimal untoward effects on serum Ca and no effects on serum P. Taken together, these observations suggest that 1 alpha-D2 deserves strong consideration as a therapeutic agent for secondary hyperparathyroidism associated with end-stage renal disease.

Animals↗
PubMed1995

Symptomatic hypercalcemia in a diabetic patient undergoing continuous ambulatory peritoneal dialysis: value of bone biopsy in the diagnosis and management.

An elderly man with diabetes mellitus and end-stage renal disease managed with continuous ambulatory peritoneal dialysis (CAPD) was hospitalized with peripheral vascular insufficiency; he developed hypercalcemia and became mentally obtunded. Lowering dialysate Ca from 3.5 mEq/L to 2.5 mEq/L, stopping calcium acetate, and ultimately hemodialysis with calcium-free dialysate did not lead to reversal of the hypercalcemia or improvement of his symptoms. The intact parathyroid hormone PTH level was 187 pg/mL, a value rarely associated with significant osteitis fibrosa. A search for other causes of hypercalcemia was unrevealing, and a iliac crest bone biopsy was done. The latter showed osteitis fibrosa, and the patient underwent parathyroidectomy. The hypercalcemia reversed quickly, and his mental symptoms slowly improved. The discussion reviews the probable causes of hypercalcemia in diabetic patient undergoing CAPD with 3.5 mEq/L dialysate calcium and using calcium-containing phosphate binders, with hyperparathyroidism certainly not the usual cause. The reason for the occurrence of significant hyperparathyroidism in the face of only modest elevation of PTH is considered. The value of bone biopsy in resolution of this problem is apparent.

Aged↗
PubMed1994

Total parenteral nutrition and its effects on bone metabolism.

Total parenteral nutrition (TPN) may affect bone metabolism in a variety of ways. These may include potential indirect effects such as on gastrointestinal hormone secretion, liver function, especially cytochrome P450 isoenzymes, metabolic biorhythms where established, and the continuous compared with the intermittent supply of nutrients. More substantial evidence exists for the reduction of bone formation, parathyroid hormone secretion, and calcitriol production in TPN patients along with high urinary calcium excretion. This review considers both aluminum loading and vitamin D sensitivity as etiologic factors and suggests that aluminum may have played a primary role in the pathogenesis of these abnormalities in bone and mineral metabolism, but that vitamin D may have potentiated the deleterious actions of aluminum. While the sources of aluminum contamination of TPN solutions have been identified and efforts are under way to reduce its contamination of TPN solutions, the persistence of low bone mass measurement in TPN patients is a problem that has been identified repeatedly, does not have a current explanation, and requires further study.

Aluminum↗
PubMed1993

Bone disease in burn patients.

Burn patients are at risk for bone disease due to aluminum (Al) exposure from use of antacids and albumin, partial immobilization, and increased production of endogenous glucocorticoids. Moreover, severely burned children are growth impaired up to 3 years after the burn. To determine the extent of bone disease, we studied nine men and three women, ages 18-41 years, with greater than 50% body surface area burn. Seven patients underwent iliac crest bone biopsy following double tetracycline labeling, one additional patient expired after a single label, and three others had postmortem specimens obtained for quantitative Al only. Serial serum and urine samples were obtained weekly until biopsy or death. All biopsied patients had reduced bone formation and osteoid area, surface, and width, with mineral apposition rate, osteoblast surface, and osteoclast number with normal eroded surfaces compared to age- and sex-matched normal ambulatory volunteers. Burn patients also had reduced bone formation, mineral apposition rate, osteoid area, and surface compared to age-matched volunteers at short-term bed rest. Serum levels of osteocalcin were low. Most patients had mild hypercalcemia but only a third had hypercalciuria. All patients had elevated Al in blood or urine; urine Al correlated inversely with serum osteocalcin. In 60% significant bone Al was detectable by stain or quantitation. Our data are compatible with burn patients having markedly reduced bone turnover. Al loading, partial immobilization, endogenous corticosteroids, and cytokine production may be among the etiologic factors.

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

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

Deferoxamine therapy and mucormycosis in dialysis patients: report of an international registry.

Fifty-nine cases of mucormycosis in dialysis patients have been reported to the registry (25 new cases and 34 previously reported cases). The presenting forms of mucormycosis included disseminated in 44%, rhinocerebral in 31%, and other forms in 25%. The diagnosis was made during life in only 39%, while the diagnosis was discovered at autopsy in 61% of the cases. The fungus, cultured in only 36%, was always Rhizopus. The infection was fatal in 86% of cases. No known risk factors for fungal infections, eg, diabetes mellitus, liver disease, splenectomy, neutropenia, steroid therapy, or other immunosuppressive therapy, were present in 70% of patients, but 78% of patients were being treated with deferoxamine. The role played by this drug and more particularly by its iron chelate, feroxamine, in the pathogenesis of mucormycosis in these patients is underscored. Because of this risk, deferoxamine therapy in dialysis patients should be limited to severe aluminum toxicity, the deferoxamine should be given at the lowest possible dose, and dialytic methods to augment the removal of feroxamine should be studied.

Adolescent↗
PubMed1991

Beta 2-microglobulin deposition in bone in chronic renal failure.

Recently, there have been reports of beta 2-microglobulin (beta 2 m) related amyloid deposition in perineural and periarticular tissues in patients receiving long-term hemodialysis, but it has been rarely described in bone. We, therefore, examined previously obtained bone biopsy specimens in patients receiving long-term hemodialysis to determine the prevalence of beta 2 m deposition in bone and to assess the relationship between beta 2 m deposits and bone histomorphometry. We found beta 2 m deposits in bone in 8% of 224 patients examined. Bone deposition of beta 2 m was absent in patients who were on dialysis for less than six years, but was present in 19% who dialyzed longer than 10 years. beta 2 m deposits were found in specimens from the iliac crest, femoral bone, tibia, vertebra and rib. In the iliac crest beta 2 m deposition was localized predominantly to the periosteum. Among these patients with beta 2 m in iliac crest periosteum, 62% had suffered a femoral neck fracture compared to only 4% of matched patients who had negative staining for beta 2 m in the iliac crest (P less than 0.001). Histologically, osteitis fibrosa seemed more common in patients positive for beta 2m than in patients negative for beta 2m deposition. We conclude that beta 2m deposition in bone is common in uremic patients who have received hemodialysis longer than 10 years. The high prevalence of femoral neck fracture in patients with beta 2m localized to the periosteum of the iliac crest suggests that this involvement may be useful to predict susceptibility to femoral fracture.

Adolescent↗
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↗
PubMed1989

Intravenous calcitriol in the treatment of refractory osteitis fibrosa of chronic renal failure.

Osteitis fibrosa, a frequent complication of chronic renal failure, is characterized by increased rates of bone formation and bone resorption due to increased secretion of parathyroid hormone (PTH). Effective treatment with oral calcitriol is often impossible in patients with osteitis fibrosa, because low doses may cause hypercalcemia. Because short-term infusions of intravenous calcitriol are capable of suppressing the secretion of parathyroid hormone in patients with uremia without causing hypercalcemia, we evaluated the effectiveness of long-term intermittent calcitriol infusions (1.0 to 2.5 micrograms three times weekly, during dialysis) in treating severe osteitis fibrosa in 12 consecutive patients on hemodialysis whose disease was refractory to conventional therapy. After a mean (+/- SE) treatment period of 11.5 +/- 1.4 months, the mean bone-formation rate declined from 1642 +/- 277 to 676 +/- 106 microns 2 per square millimeter per day (P less than 0.01) in the 11 patients who successfully completed the study. Similar reductions occurred in the osteoblastic osteoid (18 +/- 3 to 9 +/- 2 percent; P less than 0.01) and the degree of marrow fibrosis (6.2 +/- 1.7 to 3.5 +/- 1.3 percent; P = 0.01). Concomitant serum biochemical changes included increased calcium levels (2.55 +/- 0.03 to 2.67 +/- 0.05 mmol per liter; P less than 0.01), decreased alkaline phosphatase levels (489 +/- 77 to 184 +/- 32 U per liter; P less than 0.001), and decreased levels of PTH (amino-terminal, 172 +/- 34 to 69 +/- 16 ng per liter in five patients, P less than 0.03; and carboxy-terminal, 1468 +/- 467 to 1083 +/- 402 ml-eq per liter in six patients, P not significant). Although the majority of the patients had transient episodes of asymptomatic hypercalcemia, this complication could be quickly reversed by temporarily halting treatment or decreasing the dose of calcitriol. We conclude that long-term intermittent infusions of intravenous calcitriol are effective in ameliorating osteitis fibrosa in patients on dialysis. Patients whose osteitis fibrosa is refractory to oral calcitriol and who are candidates for parathyroidectomy should be considered first for intravenous calcitriol therapy.

Adult↗