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Biomedical subjects

G L Klein

Publications and source records attributed to G L Klein.

At least 73 records · Page 4Linked to original sources

Evidence of aluminum loading in infants receiving intravenous therapy.

To investigate the possibility that premature infants may be vulnerable to aluminum toxicity acquired through intravenous feeding, we prospectively studied plasma and urinary aluminum concentrations in 18 premature infants receiving intravenous therapy and in 8 term infants receiving no intravenous therapy. We also measured bone aluminum concentrations in autopsy specimens from 23 infants, including 6 who had received at least three weeks of intravenous therapy. Premature infants who received intravenous therapy had high plasma and urinary aluminum concentrations, as compared with normal controls: plasma aluminum, 36.78 +/- 45.30 vs. 5.17 +/- 3.1 micrograms per liter (mean +/- S.D., P less than 0.0001); urinary aluminum:creatinine ratio, 5.4 +/- 4.6 vs. 0.64 +/- 0.75 (P less than 0.01). The bone aluminum concentration was 10 times higher in infants who had received at least three weeks of intravenous therapy than in those who had received limited intravenous therapy: 20.16 +/- 13.4 vs. 1.98 +/- 1.44 mg per kilogram of dry weight (P less than 0.0001). Creatinine clearances corrected for weight did not reach expected adult values until 34 weeks of gestation. Many commonly used intravenous solutions are found to be highly contaminated with aluminum. We conclude that infants receiving intravenous therapy have aluminum loading, which is reflected in increased urinary excretion and elevated concentrations in plasma and bone. Such infants may be at high risk for aluminum intoxication secondary to increased parenteral exposure and poor renal clearance.

Aluminum↗

Adverse metabolic consequences of total parenteral nutrition.

Recently described metabolic complications of total parenteral nutrition (TPN) are discussed. Included are descriptions of disorders affecting the hepatobiliary system and the musculoskeletal system. The effects of TPN on the hepatobiliary system include cholestatic hepatitis and cholelithiasis; the complications affecting the musculoskeletal system include acute polymyopathy and low-turnover, osteomalacic bone disease. With the exception of the acute polymyopathy, which is probably due to essential fatty acid deficiency, the other systemic disorders may have multiple etiologies. Also summarized are the relatively recent findings of iatrogenic micronutrient deficiencies, including chromium, selenium, and molybdenum. These trace element deficiencies appear to have multisystem manifestations. Recommendations for management are discussed.

Aluminum↗

Serum levels of 1,25-dihydroxyvitamin D in children receiving parenteral nutrition with reduced aluminum content.

Both adults and children receiving total parenteral nutrition (TPN) have been found to have low serum levels of 1,25(OH)2-vitamin D [1,25(OH)2D]. Many of these were subsequently found to have inadvertently received large quantities of aluminum in the TPN solution. Since aluminum administration to dogs is associated with a fall in serum 1,25(OH)2D levels, the present study was designed to prospectively follow serum levels of this sterol while patients received a TPN solution low in aluminum. Nine children received a TPN solution comparable to that previously administered to children who demonstrated low serum levels of 1,25(OH)2D, except for a moderately reduced phosphorus and markedly reduced aluminum content. Serum was obtained during the first and fourth weeks of TPN treatment and analyzed for 1,25(OH)2D, 25-hydroxyvitamin D [25(OH)D], immunoreactive parathyroid hormone (iPTH), calcium, and phosphorus. Results revealed normal or high serum levels of 1,25(OH)2D and normal levels of iPTH, calcium, phosphorus, and 25(OH)D. Thus, low aluminum-containing TPN does not produce a fall in serum 1,25(OH)2D, providing evidence that aluminum may have been a factor in causing the reduced serum 1,25(OH)2D in those children previously receiving TPN.

Aluminum↗

Cystic fibrosis mistaken for idiopathic biliary atresia.

Previous reports of prolonged jaundice in cystic fibrosis have not described operative and histopathological findings in the liver and biliary tree. In the two cases reported here, obstructive jaundice in the neonatal period was associated with anatomical evidence of intra- or extrahepatic biliary obstruction. Hepatoportoenterostomy, a surgical procedure that is not without complications, was performed on one of the patients for biliary atresia before the diagnosis of cystic fibrosis was suspected. Prolonged obstructive jaundice may be an early manifestation of cystic fibrosis and may resolve without operative management. A sweat test should be performed on all patients with prolonged obstructive neonatal jaundice to rule out cystic fibrosis.

Bile Ducts↗

Metabolic bone disease associated with total parenteral nutrition.

Patients receiving long-term treatment with total parenteral nutrition often develop bony abnormalities characterized by patchy osteomalacia and low bone turnover. The patients present evidence of physiologic hypoparathyroidism, although low levels of iPTH cannot entirely explain the osteomalacia. Abnormally low serum levels of 1,25(OH)2-vitamin D have been demonstrated, but the significance of these reduced levels in the pathogenesis of the bone lesions is not defined. Aluminum has been detected in large quantities in the plasma, urine, and bone of some patients treated with TPN, and there is mounting evidence that aluminum may be associated with skeletal pathology, particularly osteomalacia. There is, however, no clear documentation that aluminum accumulation produces the skeletal lesions observed, although it could be a contributing factor. There has been the unusual empiric observation that the removal of vitamin D2 from the infusate is associated with a decrease in the quantity of unmineralized osteoid in TPN patients. A possible role of vitamin D2 in producing osteomalacia is not easy to understand since normal serum levels of 25(OH)-D2, the circulating form of vitamin D2, have been reported. The long-term consequences of intravenous nutritional support for many aspects of metabolism remain unknown. Administration into the systemic circulation of predetermined quantities of calcium and phosphorus via a route that bypasses their passage across the intestinal mucosa, the portal system and the liver may have adverse consequences. It is possible that bypassing homeostatic mechanisms may affect bone formation and metabolism or lead to alterations in vitamin D sterols. Alternatively, a deficiency of an essential trace metal or the accumulation of a toxic trace substance could be responsible for the bony abnormalities. Much remains to be clarified concerning calcium homeostasis and bone disease during total parenteral nutrition. Among various possible factors, it seems likely that the significance of the low levels of 1,25(OH)2-vitamin D and of the accumulation of aluminum in this condition will soon be clarified.

Adult↗

Calcitonin levels in sera of infants and children: relations to age and periods of bone growth.

Serum calcitonin levels have been reported to be elevated in premature and newborn infants, a period of maximal rate of bone growth. To determine whether calcitonin remains elevated during the first year of life, a time of rapid extrauterine bone growth, fasting serum calcitonin levels were determined in 31 hospitalized infants and children ages 24 weeks gestation to 6 years. Calcitonin levels were significantly higher in the premature and newborn infants than in the first year of life. However, calcitonin levels in the first year of life were still significantly higher than during the second to sixth years. This fall in serum calcitonin levels parallels the age-related decline in rate of bone growth. One can speculate that the changes in serum calcitonin levels during the first year of life may indicate that it plays a role in bone growth or mineralization. However, the possibility that the changes in calcitonin levels are unrelated to changes in bone growth or mineralization has not been ruled out.

Age Factors↗

Hepatic aluminum accumulation in children on total parenteral nutrition.

Five children receiving long-term total parenteral nutrition (TPN) containing casein hydrolysate as the protein source underwent percutaneous liver biopsies because of the development of cholestasis and abnormal liver function tests. All five demonstrated moderate to severe histopathologic changes. In addition, hepatic aluminum content was determined to be markedly elevated in all cases. Although the hepatotoxicity of aluminum is as yet undetermined, deposition of other metals has been associated with liver damage, and aluminum has been associated with pathology in other tissues. Thus, the possibility that aluminum deposition may play a role in the pathogenesis or exacerbate the course of liver dysfunction associated with TPN should be considered.

Aluminum↗

Aluminum is associated with low bone formation in patients receiving chronic parenteral nutrition.

Patients treated with chronic total parenteral nutrition may develop metabolic bone disease. We evaluated 22 bone biopsy specimens from 16 patients. Compared with those of age- and sex-matched normal controls, these specimens had significantly higher osteoid area and lower total bone area and bone formation rate, as measured by double tetracycline labels. Aluminum was found in specimens from the 14 patients receiving casein hydrolysate but not in the two receiving amino acids as their nitrogen source. The reduced bone formation correlated inversely with the logarithm of the aluminum level. Aluminum was localized to the surface of mineralized bone; tetracycline uptake was absent at those sites. These bone findings are similar to those from aluminum intoxicated patients on hemodialysis. Both groups also have low parathyroid hormone levels. Thus, aluminum appears to be an important pathogenic factor in the osteodystrophy of patients receiving dialysis or total parenteral nutrition.

Adult↗

Aluminum loading during total parenteral nutrition.

Patients on long-term total parenteral nutrition were found to have elevated aluminum (AI) levels in bone, and plasma, with the casein in the total parenteral nutrition solution the source of A1. Substitution of amino acids for casein was followed by a fall in urinary and plasma A1. Thus, parenteral loading with A1 increases tissue A1, particularly in bone. Whether A1 accumulation contributes to bone disease remains unclear, but the prolonged use of casein in total parenteral nutrition solutions may be inadvisable.

Adult↗

Reduced serum levels of 1 alpha,25-dihydroxyvitamin D during long-term total parenteral nutrition.

Painful bone disease, characterized by patchy osteomalacia and inactive bone, can develop in patients treated with total parenteral nutrition for more than 3 months. Serum levels of 1 alpha,25-dihydroxyvitamin D (1 alpha, 25(OH)2D), 24,25-dihydroxyvitamin D and 25-hydroxyvitamin D were measured in seven adults and five children treated with parenteral nutrition for 9 to 60 months. Serum levels of 1 alpha, 25(OH)2D were markedly reduced, while levels of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were normal. Serum calcium and phosphorus levels were normal or slightly increased, and immunoreactive parathyroid hormone levels were normal or low. Renal function was normal or minimally reduced. Skeletal symptoms disappeared and serum 1 alpha, 25(OH)2D levels rose to normal in one patient when nutrient infusions were discontinued for 6 weeks. Removal of calcium from the nutrient solution for 2 to 4 days was associated with no change in serum 1 alpha, 25(OH)2D in two patients. The cause of the reduction in serum levels of 1 alpha, 25(OH)2D and its role in the pathogenesis of bone disease in these patients remain uncertain.

Adult↗

A Medical Allergy Profile (MAP) card.

A Medications and Allergy Profile (MAP) card was created that lists instructions and the patient's individual drug regimen. This card is wallet-size and lists the patient's medications with schedule dosage. it also indicates allergies, usual peak flow, theophylline level and steroid dependence. Twenty-four age-matched asthmatics were asked to name their medications schedule and dosage. They were then assigned either to receive a MAP card or to be controls. There was no significant difference between the MAP card group and the controls in the accuracy of their responses initially but when the questions were repeated an average of 3.2 months later only the MAP group showed a significant improvement in naming medication, dose and schedule (p less than 0.001, 0.005, and 0.005, respectively). The MAP card can improve patients' comprehension of their drug regimen and improves medical communication.

Child↗