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Biomedical subjects

N D Adams

Publications and source records attributed to N D Adams.

12 recordsLinked to original sources

Nephrocalcinosis.

The pathogenesis of NC in VLBW infants appears to be multifactorial. The vulnerability of extreme immaturity and the underdevelopment of renal function may be the most important variables. In some ways, we view this problem as similar to that of retinopathy of prematurity. (Clearly the exposure of the retina to high partial pressures of oxygen contributes to the development of retinopathy of prematurity but other variables--some known, such as an immature retina, and others not yet defined--must be present.) Hypercalciuria is common in the VLBW infant, yet not all develop NC. Decreased glomerular filtration rate, low citrate excretion, and frequently an alkaline urine are in part due to the immaturity of renal function of these infants. The need for prolonged hyperalimentation resulting in increased oxalate excretion and the development of BPD frequently requiring diuretics that may cause phosphaturia and magnesium depletion and that may increase calcium excretion are more common in the smallest and sickest of premature infants. Even transient insults to the kidneys, such as hypoxia or hypotension or the use of nephrotoxic drugs that provoke tubular injury and cell death with the probability of crystal formation and growth by way of heterogeneous nucleation, are likely to occur more frequently in this vulnerable population.

Calcium

Effect of high calcium and phosphorus intake on mineral retention in very low birth weight infants chronically treated with furosemide.

The treatment of premature infants with the diuretic furosemide appears to be a contributory factor in the development of metabolic bone disease presumably because of furosemide-induced hypercalciuria. In this study, we measured calcium and phosphorus balance in furosemide-treated very low birth weight infants (VLBW) infants with bronchopulmonary dysplasia (BPD) who were fed a specialized premature formula containing increased amounts of calcium and phosphorus. Furosemide-treated infants received 166 +/- 37 mg/kg/day and retained 80 +/- 34 mg/kg/day of calcium, and 87 +/- 19 mg/kg/day and retained 52 +/- 14 mg/kg/day of phosphorus. The amounts retained were approximately 65% of the calcium and 72% of the phosphorus requirements for in utero mineral accretion. Compared to a group of similarly fed VLBW infants without BPD and not treated with the diuretic, the furosemide-treated infants excreted a larger percent of the calcium intake in the urine but had similar total urinary calcium and phosphorus losses (mg/kg/day) and serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone (PTH) levels. From the latter two findings, we suggest that the extra mineral content of the formula may have promoted bone mineralization and prevented the occurrence of secondary hyperparathyroidism.

Calcium

Absence of anion gap metabolic acidosis in severe methanol poisoning: a case report and review of the literature.

Methanol poisoning in humans is characterized by a latent period with subsequent development of anion gap metabolic acidosis and blindness. We describe a patient with potentially lethal methanol ingestion as evidenced by an admission serum methanol level of 403 mg/dL and sustained serum methanol levels greater than 50 mg/dL for more than 18 hours after ingestion, despite hemodialysis therapy. That anion gap metabolic acidosis or visual impairment did not develop in this patient was attributed to documented prior ethanol ingestion (admission serum ethanol level of 158 mg/dL) and continued ethanol administration during hospitalization (sustained serum ethanol levels greater than 100 mg/dL). This case demonstrates the ability of ethanol to inhibit the metabolism of methanol to formic acid in humans. This inhibition was achieved without induction of lactic acidosis. Thus this case documents the efficacy of ethanol therapy in patients with methanol poisoning.

Acid-Base Equilibrium

Review: Renal osteodystrophy--pathogenesis and treatment.

Histologic bone changes of osteitis fibrosa and osteomalacia are commonly present in patients with end-stage renal disease. Although many patients are not symptomatic from these bone changes, some patients are severely disabled. Altered metabolism of vitamin D, calcium, phosphorus, and parathyroid hormone occurs in renal failure and contributes to the development of uremic bone disease. This article reviews the current theories of pathogenesis and treatment of renal osteodystrophy. In addition, the clinical presentation, pathogenesis, and treatment of the various aluminum-associated osteomalacic syndromes in uremia are discussed.

Aluminum

Renal osteodystrophy--pathogenesis and treatment.

Histologic bone changes of osteitis fibrosa and osteomalacia are commonly present in patients with end-stage renal disease. Although many patients are not symptomatic from these bone changes, some patients are severely disabled. Altered metabolism of vitamin D, calcium, phosphorus, and parathyroid hormone occurs in renal failure and contributes to the development of uremic bone disease. This article reviews the current theories of pathogenesis and treatment of renal osteodystrophy. In addition, the clinical presentation, pathogenesis, and treatment of the various aluminum-associated osteomalacic syndromes in uremia are discussed.

Aluminum

The calciuria of increased fixed acid production in humans: evidence against a role for parathyroid hormone and 1,25(OH)2-vitamin D.

We measured mineral and acid balances, serum iPTH, urinary cAMP/creatinine, and plasma concentrations of 25OHD and 1,25(OH)2D in 7 healthy adults during control conditions and during increased fixed acid production achieved either by the administration of NH4Cl (N = 3) or by increased dietary protein intake (N = 4). When acid production was increased, the subjects were in positive acid balance and negative Ca balance because of increased urinary Ca excretion. Serum iPTH fell slightly but urinary cAMP and the plasma levels of vitamin D metabolites did not change. W conclude that the accelerated skeletal and urinary losses of Ca that occur when fixed acid production is increased are not contributed to nor compensated for by the parathyroid-vitamin D endocrine systems.

Acids

Ethanol induced secretion of calcitonin in chronic renal disease.

Whisky (25-50 ml) increased plasma levels of immunoreactive calcitonin (iCT) in seventeen of nineteen patients with chronic renal failure. The effect was greater in patients with high levels of iCT than in those with normal levels. Changes in plasma iCT were not related to changes in calcium, phosphate or immunoreactive gastrin, but were inhibited by the prior administration of propranolol.

Calcitonin

The interrelationships among prolactin, 1,25-dihydroxyvitamin D, and parathyroid hormone in humans.

Serum PRL, parathyroid hormone (PTH), and plasma 1,25-dihydroxyvitamin D [1,25(OH)2D]concentrations were measured in 6 women and 2 men with hyperprolactinemia, 6 normal men and 7 normal women, 4 men and 4 women with primary hyperparathyroidism, and 16 men and 4 women with Ca nephrolithiasis. Plasma 1,25(OH)2D and serum parathyroid hormone (PTH) concentrations were normal in the women and men with hyperprolactinemia. In patients with primary hyperparathyroidism and elevated serum PTH, plasma 1,25(OH)2D concentrations were elevated but serum PRL levels were normal. Likewise, serum PRL levels were normal in patients with Ca nephrolithiasis who had significantly elevated plasma, 1,25(OH)2D concentrations and normal serum PTH concentrations. Thus, hyperprolactinemia due to pituitary adenoma or idiopathic hypersecretion is not accompanied but elevated plasma concentrations of 1,25(OH)2D.

Adenoma

The effects of dihydrotachysterol therapy on the measurement of plasma 1,25-(OH)2-vitamin D in humans.

Anephric patients have undetectable plasma concentrations of 1,25-(OH)2-D, but when anephric patients are treated with DHT2 (Hytakerol), their plasma contains a substance that is co-purified with and displaces authentic 3H-1,25(OH)2-D3 from its intestinal cytoplasmic receptor. The concentration of this substance in the plasma of anephric patients taking DHT2 is proportional to the administered daily dose of DHT2 per kilogram body weight. When DHT2 therapy is discontinued, the substance disappears from plasma with an average t 1/2 of about 8 days.

Dihydrotachysterol

Physiological and pharmacological aspects of 24,25-dihydroxycholecalciferol in man.

The present study describes the response to small oral doses (1--10 microgram/day) of 24,25-DHCC in man. Contrary to expectation, 24,25-DHCC was as potent as 1,25-DHCC in increasing intestinal absorption of calcium both in normal persons and in patients with a variety of disorders of calcium metabolism. Despite this increase in intestinal absorption, plasma and urine calcium did not increase after 24,25-DHCC as they did after 1,25-DHCC. Metabolic balance studies showed calcium balances to increase by 1.6 to 11.5 mmoles/day in 5 of the 6 patients studied. 24,25-DHCC increased intestinal absorption of calcium equally well in anephric patients, suggesting that conversion of 24,25-DHCC to 1,24,25-trihydroxycholecalciferol by the kidney cannot be the sole mechanism by which 24,25-DHCC expresses biological activity, even though in vitamin D deficient rats nephrectomy does abolish the ability of large doses of 24,25-DHCC to increase calcium absorption. It is concluded that 24,25-DHCC may be a calcium-regulating hormone in man. In view of the effects demonstrated here and its relatively high concentration in plasma and slow turnover rate, 24,25-DHCC has the properties that might be ideal for a long-acting stimulator of bone mineralisation. Further work is needed to explain why 24,25-DHCC has effects in man which are not readily seen in other species.

Bone Development