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Biomedical subjects

J E Heubi

Publications and source records attributed to J E Heubi.

At least 37 records · Page 2Linked to original sources
PubMed1996

Intestinal calcium absorption of women during lactation and after weaning.

We investigated whether intestinal calcium absorption and serum 1,25-dihydroxycholecalciferol (calcitriol) concentrations are higher in women during lactation and after weaning to compensate for calcium lost in breast milk. Measurements were obtained at 4.6 mo postpartum in 24 lactating women and 24 nonlactating women, at 9.6 mo postpartum in 24 lactating women (2.6 mo after complete weaning) and 24 nonlactating women. One-half of the women in each group were randomly assigned to receive 1 g supplemental Ca/d as calcium carbonate. Fractional calcium absorption was measured by using stable isotopic tracers 42Ca and 44Ca. Fractional absorption was 0.32+/-0.02 (+/-SEM) in both lactating and nonlactating women, but was higher in lactating women after weaning (0.37+/-0.02) compared with nonlactating postpartum control subjects (0.31+/-0.02). These effects were independent of calcium intake. Changes in serum calcitriol paralleled changes in fractional absorption. There were no differences in calcitriol concentrations between lactating and nonlactating women, but calcitriol was greater in women after weaning compared with postpartum control subjects. Lactating women who had resumed menses had higher fractional absorption and serum calcitriol than did lactating women who had not. Serum calcium and phosphorus concentrations were greater in lactating compared with nonlactating women; there were no differences between groups after weaning. We conclude that lactation stimulates increases in fractional calcium absorption and serum calcitriol, but the responses are only apparent after weaning or the resumption of menses.

Adult↗
PubMed1995

Resting energy expenditure and body composition in pediatric HIV infection.

One of the most striking features of HIV disease is the "wasting syndrome" or failure to thrive. Eighty percent of all perinatally HIV-infected children fail to grow normally. OBJECTIVE. Because severe malnutrition increases the morbidity of HIV infection and may shorten the already limited life expectancy of this population, we assessed resting energy needs, body composition, and nutrient intake in nine children perinatally HIV-infected, age 4 months to 4 years. DESIGN. Subjects were studied using measurements of resting energy expenditure (REE) by indirect calorimetry, body composition measurements by dual-energy X-ray absorptiometry (DEXA) and skinfolds, nutrient intake analysis by 24-hour recall, and serum protein levels. The HIV-infected children were free of secondary opportunistic infection at the time of the study. Subjects were reevaluated within the following year. RESULTS. REE correlated well (r = .856) with the predicted value from the World Health Organization (WHO) equation for basal energy expenditure. Measurement of percent body fat by skinfolds correlated well with DEXA percent body fat (r = .61). There was no significant difference between body fat assessed from skinfolds compared to published age-matched standards. All subjects met their recommended dietary allowance (RDA) for calories and protein. All subjects had adequate visceral protein stores for age. CONCLUSION. Perinatally infected children were not hypermetabolic when not secondarily infected and were able to maintain normal growth with the provision of adequate nutrition.

Basal Metabolism↗
PubMed1994

The prevalence of hepatitis C virus (HCV) in infants and children after liver transplantation.

Hepatitis C virus (HCV) is an important cause of liver injury following liver transplantation in adults. We hypothesized that the prevalence of HCV infection in children following liver transplantation would be lower than the prevalence in adults after liver transplantation because HCV-related liver disease leading to liver transplantation in children is low and children require less blood products than adults during transplantation. We therefore performed a cross-sectional study to determine the prevalence of HCV infection in children who had undergone liver transplantation. Serum samples were obtained from 62 of 65 (95.4%) consecutive patients surviving for more than six months after transplantation. Using a second-generation enzyme-linked, immunosorbent assay (ELISA-2) and a second-generation recombinant immunoblot assay (RIBA-II), antibodies to HCV were detected in 5.1% (3 of 59) of the subjects. Using a single-step, polymerase chain reaction (PCR), HCV RNA was detected in 6.2% (4 of 62). All HCV-positive children had undergone liver transplantation before the initiation of routine screening for HCV in blood donors; overall 30 patients were transplanted prior to routine screening of blood products for HCV. The prevalence of HCV in infants and children after liver transplantation in our study is substantially less than the rates reported in adults. This difference may be due, in part, to the lower volume of blood product exposure and to the fact that children, as opposed to adults, rarely have chronic HCV infection as a cause of end-stage liver disease.

Adolescent↗
PubMed1994

The spectrum of bile duct complications in pediatric liver transplantation.

It has been noted that reduced-size liver transplants are associated with increased rates of biliary complications, and it has been suggested that some of these complications can be handled nonoperatively. In a 6-year period, 91 orthotopic liver transplants were performed in 77 children. The medical records were reviewed to analyze the effect of reduced-size grafts on the incidence of bile duct complications and to investigate the utility of interventional radiology techniques for treatment. Forty-two children received 47 whole-organ transplants, and 35 children received 44 reduced-size transplants. The median age and weight were greater for children receiving whole-organ transplants (age, 4.25 years; weight, 16 kg) than for those receiving reduced-size grafts (age, 1.0 year; weight, 8 kg). The overall incidence of bile duct complications was 19.5% (n = 15). The incidence was not different between the whole organ group (17%) and the reduced-size group (16%). Four of the children with bile duct complications had associated hepatic artery thrombosis, two of whom had another transplant. Complications included anastomotic stricture (n = 6), anastomotic leak (n = 5), intraparenchymal biloma (n = 3), and multiple strictures (n = 1). Twelve of 15 children presented within 3 months of transplantation. Six children had initial percutaneous drainage or placement of transanastomotic stents (external). Operative repair was eventually required for all 15 children, three of whom received a second transplant. There was a 40% incidence of cytomegalovirus infection involving the liver or extrahepatic bile ducts near the time of presentation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Calcium kinetics in lactating women with low and high calcium intakes.

Absorption of calcium and its mobilization from bone during lactation are important for delivery of calcium to breast-feeding infants; whether calcium intake offsets bone resorption is not known. We hypothesized that calcium absorption is increased in lactation and greater in women on low calcium diets, resulting in similar rates of bone resorption and accretion. Calcium absorption and kinetic indexes were calculated by using two stable isotopic tracers in 8 women; 6 were studied both during lactation and nonlactation. Women consumed low calcium diets, with half receiving supplemental calcium. Intestinal absorption was related to serum 1,25-dihydroxyvitamin D and did not increase during lactation. Despite decreased urinary calcium excretion during lactation, especially in women with low calcium intake, net balance tended to be lower during lactation. Mean residence time decreased and bone resorption exceeded accretion in almost all lactating women. Calcium need for milk production appears to be met by decreased urinary excretion and increased bone resorption, and not by increased intestinal absorption.

Adult↗
PubMed1994

Downregulation of taurocholate transport by ileal BBM and liver BLM in biliary-diverted rats.

The enterohepatic circulation of bile salts may be substrate dependent. We hypothesize that decreased intestinal delivery of bile salts results in downregulation of ileal and hepatocyte bile salt transport in the biliary-diverted rat. Maximal velocity (Vmax) of taurocholate transport by ileal brush-border membrane (BBM) vesicles was downregulated in the bile-diverted animals by 45.5% (559.9 +/- 57.8 pmol.mg protein-1.min-1 in bile-diverted rats vs. 1,026.6 +/- 170.9 pmol.mg protein-1.min-1 in shams). Similarly, taurocholate transport Vmax by hepatocyte basolateral membrane (BLM) was downregulated by 37.8% (2.62 +/- 0.18 pmol.mg protein-1.min-1 in bile-diverted rats vs. 6.93 +/- 0.41 pmol.mg protein-1.min-1 in shams). Cholesterol content (mumol/mg protein) of the membranes was increased in both BBM (0.478 +/- 0.055 vs. 0.272 +/- 0.029) and BLM (0.410 +/- 0.052 vs. 0.294 +/- 0.044) in diverted rats compared with shams. Fluorescence anisotropy was significantly higher in diverted animals compared with shams for both BBM (0.2333 +/- 0.001 vs. 0.2120 +/- 0.004) and BLM (0.1524 +/- 0.002 vs. 0.1426 +/- 0.005). We conclude that biliary diversion in the rat leads to downregulation of both ileal BBM and hepatocyte BLM taurocholate transport. Alterations in transporter expression caused by diversion may, in part, be mediated by changes in membrane lipid composition or fluidity.

Animals↗
PubMed1994

Effect of fasting on the enterohepatic circulation of bile acids in rats.

Fasting Sprague-Dawley rats for 72 h resulted in inhibition of bile salt synthesis, reduced bile flow and bile salt secretion rate, and reduced duodenal and portal venous bile acid concentrations. The initial rate of ileal brush border membrane (BBM) taurocholate (TC) uptake was markedly reduced in the fasted group (45% of control). TC uptake by BBM was saturable, with similar maximal transport velocity for the fasted rats and controls (1.69 +/- 0.06 and 1.62 +/- 0.017 nmol.mg protein-1.min-1, respectively) but higher Michaelis-Menten constant for fasted rats than for controls (96.9 +/- 20.0 and 54.9 +/- 10.2 microM, respectively). Hepatic basolateral membrane (BLM) TC uptake was enhanced by 65% in fasted animals. Transport kinetics in BLM had a similar Michaelis-Menten constant for fasted rats and controls (31.6 +/- 8.2 and 27.3 +/- 4.7 microM, respectively), and maximal transport velocity was higher for fasted rats than for controls (1.84 +/- 0.017 and 1.11 +/- 0.014 nmol.mg protein-1.min-1). The cholesterol-to-phospholipid ratio and fluorescence anisotropy in BLM of fasted rats decreased, and the cholesterol-to-phospholipid ratio and fluorescence anisotropy increased in ileal BBM. Alterations in the enterohepatic circulation of bile acids with fasting may alter expression of transport proteins for bile salts by direct effects on synthesis or indirectly through membrane lipid compositional changes.

Animals↗
PubMed1994

Effect of orthotopic liver transplantation on bone mineral content and serum vitamin D metabolites in infants and children with chronic cholestasis.

Almost all infants and children with chronic cholestasis have osteopenia. We evaluated the effect of orthotopic liver transplantation on bone mineral content and serum 25(OH)-vitamin D-[25(OH)D]-of nine infants and children (five girls; age, 6 to 21 mo at the time of orthotopic liver transplantation) with end-stage liver disease resulting from chronic cholestasis. We hypothesized that after orthotopic liver transplantation, decreased bone mineral content will recover and the serum 25(OH)D level will either normalize or remain normal in those who were previously vitamin D deficient or sufficient, respectively. All had subnormal bone mineral content before transplant. On long-term follow-up (> 4 mo) of seven patients, bone mineral content normalized in all between 6.5 and 19 mo after transplant, with a mean of 11.2 +/- 4.5 mo. In six patients with normal serum 25(OH)D levels before orthotopic liver transplantation, the serum 25(OH)D levels had declined markedly 1 to 2 mo after transplant, followed by return to normal by 3 to 6 mo. Low serum 25(OH)D levels (< 15 ng/ml) in three patients before orthotopic liver transplantation normalized after transplant. Although there was no correlation between bone mineral content and serum 25(OH)D level before transplant, sustained normal serum 25(OH)D and 1,25(OH)2D levels preceded or accompanied normalization of bone mineral content in the seven patients available for long-term follow-up. We conclude that (a) in infants and children younger than 2 yr with chronic cholestasis, bone mineral content normalizes approximately 11 mo after orthotopic liver transplantation. This normalization is preceded by a sustained period of normal serum 25(OH)D levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density↗
PubMed1993

Multicenter trial of d-alpha-tocopheryl polyethylene glycol 1000 succinate for treatment of vitamin E deficiency in children with chronic cholestasis.

BACKGROUND: Malabsorption and deficiency of vitamin E causing neurological degeneration are common consequences of chronic childhood cholestatic liver disease. The objective of this study was to determine the long-term efficacy and safety of d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) in correcting vitamin E deficiency in children with chronic cholestasis who were unresponsive to other forms of oral vitamin E. METHODS: Sixty vitamin E-deficient children with chronic cholestasis unresponsive to 70-212 IU.kg-1.day-1 of oral vitamin E were entered into a trial at eight centers in the United States. After initial evaluation, treatment was started with 25 IU.kg-1.day-1 of TPGS. Vitamin E status, neurological function quantitated by a specific scoring system, and clinical and biochemical parameters were monitored during therapy. RESULTS: All children responded to TPGS with normalization of vitamin E status. Neurological function, which had deteriorated before entry in the trial, improved in 25 patients, stabilized in 27, and worsened in only 2 after a mean of 2.5 years of therapy. No adverse effects were observed. CONCLUSIONS: TPGS (20-25 IU.kg-1.day-1) appears to be a safe and effective form of vitamin E for reversing or preventing vitamin E deficiency during chronic childhood cholestasis.

Adolescent↗
PubMed1993

Fat-soluble vitamin deficiency in infants and children.

Fat-soluble vitamin deficiency is known to result in various complications that may be prevented if the problem is recognized and managed appropriately. In infants and children with chronic cholestasis, replacement therapy of the fat-soluble vitamins, vitamins A, D, E, and K, may prove extremely difficult because low concentrations of intraluminal bile acids lead to malabsorption of these compounds and other fat-soluble substances. Recent progress in the use of a water-soluble form of vitamin E, d-alpha-tocopheryl polyethylene glycol-1000 succinate, has enabled correction of vitamin E-deficiency states in these patients. It has also allowed for the admixture and coadministration of other fat-soluble vitamins and compounds in d-alpha-tocopheryl polyethylene glycol-1000 succinate to enhance their absorption. For managing vitamin K deficiency, similar success has been achieved using a vitamin K compound solubilized in glycocholate and lecithin. Vitamin A deficiency has been implicated in the higher incidence of childhood mortality and morbidity in Third World countries. Increased risk of childhood cancer has recently been associated with intramuscular injection of vitamin K to newborns. Finally, it is worth noting that among the pediatric population, exclusively breastfed infants, in general, are at risk for hypovitaminosis D, and at even greater risk in the absence of adequate exposure to sunlight or when the maternal diet is not sufficient to provide for vitamin D requirements.

Breast Feeding↗
PubMed1993

Resolution of liver biopsy alterations in three siblings with bile acid treatment of an inborn error of bile acid metabolism (delta 4-3-oxosteroid 5 beta-reductase deficiency).

Identical male twins and their brother, cholestatic from birth, with delta 4-3-oxosteroid 5 beta-reductase deficiency, were studied by serial liver biopsy. Spectrometry documented defective primary bile acid synthesis and markedly increased levels of atypical oxo and allo bile acids in urine and serum. Hepatocellular cholestasis and giant-cell transformation resolved in parallel with clinical and biochemical recovery during oral bile acid administration. In the twins, portal fibrosis stabilized at a mild level; they are well as 5-yr-olds at this writing. Follow-up biopsy in their brother at 8 mo was normal, and he is doing well at 3 yr of age. Hepatic ultrastructural alterations in all three were characterized by abnormalities of bile canaliculi including small bile plugs, diverticulae and latticelike elaborations of hepatocellular membranes adjacent to bile canaliculi that were shown to have resolved completely on subsequent biopsies. Eight additional cases have been detected on urine screening; only two of these patients have survived, on bile acid therapy. Early diagnosis and treatment improves the prognosis of this otherwise lethal inborn error of bile acid synthesis.

Bile Acids and Salts↗
PubMed1993

Bone mineral content in infants and children with chronic cholestatic liver disease.

OBJECTIVE: To assess bone mineral content (BMC) status and serum vitamin D metabolite levels of infants and children with chronic cholestatic liver disease. To determine if severity of bone disease in these patients correlates with serum vitamin D metabolite levels. METHODOLOGY: We measured radial BMC with the use of a single-beam photon absorptiometer and serum vitamin D metabolite levels in 56 patients with chronic cholestasis seen at our institution from 1985 through 1991. Patients were divided into two groups according to age. RESULTS: In group 1 (n = 37; age 2 to 22 months), decreased levels of BMC were seen as early as the first few months of life, with sharp decline observed with increasing age (approaching 3 to 5 standard deviations [SD] below the mean, P < .0003). Older patients (group 2, n = 19; age 2 to 20 years) had BMC values which clustered between 2 and 4 SD below the mean throughout the age range. Although a downward trend also was noted with increasing age, this was not statistically significant. Despite correction for weight-age or height-age, BMC was decreased in most of these patients. No correlation between severity of osteopenia and serum levels of 25(OH)-vitamin D and 1,25(OH)2-vitamin D was observed in either infants or older children. CONCLUSIONS: Decreased bone mineralization, as a complication of chronic cholestatic conditions, is a disease process that begins early in infancy, rapidly worsens with increasing age and hepatic dysfunction, and remains relatively stable in children with more stable liver disease.

Adolescent↗
PubMed1992

Complications of percutaneous liver biopsy in children.

To determine the frequency and nature of complications after liver biopsy and whether risk factors could be identified to predict these complications, the medical records of all patients (age, 1 week to 28 years) who underwent a percutaneous liver biopsy at Children's Hospital over a 6-year period (1981-1986) were reviewed. Data were collected from 469 (97%) of 483 eligible charts. Twenty-one patients (4.5%) experienced major complications including bile leak (n = 3, 0.6%), prolonged drainage of ascitic fluid (n = 1, 0.2%), pneumothorax (n = 1, 0.2%), bleeding requiring transfusion (n = 13, 2.8%), and death (n = 3, 0.6%). A subgroup of patients (n = 37) with cancer or bone marrow transplantation was found to be at a nearly fivefold greater risk for transfusion than patients with other diagnoses (P = 0.02). All three deaths in previously stable patients occurred in this same high-risk group of patients with cancer or bone marrow transplantation (P less than 0.001). Two deaths resulted from disseminated intravascular coagulation and one from bleeding. Diagnosis, age, number of percutaneous passes, and prebiopsy coagulation studies were not predictive of subsequent complications. It is concluded that bleeding that requires transfusion is the most common liver biopsy complication and that it occurs more frequently in children than previously reported. Children with cancer or those who have undergone bone marrow transplantation are at a greater risk for bleeding and death following percutaneous liver biopsy.

Abdominal Pain↗
PubMed1992

Ileal resection/dysfunction in childhood predisposes to lithogenic bile only after puberty.

Children with ileal resection/dysfunction since infancy have bile that is not supersaturated with cholesterol. Five sexually mature subjects (age 16-19 years) who had been previously investigated in childhood (age 4-9 years) were studied. Gallstones were found in one. Bile rich duodenal aspirates were analyzed for lipid content (molar fraction) and the cholesterol saturation index was calculated. In the postpubertal subjects, a significantly higher proportion of biliary cholesterol (22.0% +/- 4.8% vs. 3.2% +/- 0.6% and 5.7% +/- 0.5%, P less than 0.005) and significantly lower bile acids (58.1% +/- 3.9% vs. 79.7% +/- 2.3% and 78.2% +/- 1.9%, P less than 0.005) were found compared with the initial (prepubertal) samples or in samples from 20 healthy young adults. The cholesterol saturation index was significantly higher (3.1 +/- 0.7 vs. 0.6 +/- 0.1 and 1.1 +/- 0.1, P less than 0.005) whereas phospholipid content did not change (19.9% +/- 1.6% vs. 17.1% +/- 1.8% and 16.6% +/- 1.6%) as compared with themselves before puberty and as healthy young adults, respectively. It was concluded that children with ileal resection/dysfunction do not appear at risk for cholesterol cholelithiasis before puberty; however, the development of biliary cholesterol supersaturation after puberty may predispose them to gallstone formation in adulthood.

Adolescent↗
PubMed1992

d-Alpha-tocopheryl polyethylene glycol-1000 succinate enhances the absorption of vitamin D in chronic cholestatic liver disease of infancy and childhood.

Rickets and osteopenia, common problems in chronic childhood cholestasis, have been attributed to vitamin D malabsorption leading to reduced serum levels of 25(OH)-vitamin D. d-alpha-Tocopheryl polyethylene glycol-1000 succinate (TPGS), a water-soluble form of vitamin E, forms micelles at low concentration. We evaluated the potential role of TPGS in enhancing vitamin D absorption in eight children (aged 5 mo to 19 y) with severe chronic cholestasis (three extrahepatic biliary atresia, three nonsyndromic intrahepatic cholestasis, and two Alagille syndrome). To evaluate vitamin D absorption, the subjects received vitamin D3 1000 IU/kg (maximum dose of 50,000 IU); they then received the same dose of vitamin D3 mixed with TPGS (25 IU/kg). Serial serum vitamin D3 levels and areas under the curve were measured. All patients had enhanced absorption of vitamin D when it was administered in a mixture with TPGS. Mean area under the curve for serum vitamin D3 was 403.0 +/- 83.1 nmol x h/L (155.6 +/- 32.1 ng x h/mL), with a mean rise above baseline of 13.5 +/- 1.8 nmol/L (5.2 +/- 0.7 ng/mL) with vitamin D/TPGS compared with no rise when vitamin D was given alone (both p less than 0.001). Seven patients have been followed for at least 3 mo while receiving the vitamin D/TPGS combination. Those with initially low serum 25(OH)-vitamin D levels (less than 37.5 nmol/L or 15 ng/mL) had normalization (range 37.5-146 nmol/L) within 1 mo, whereas those with initially normal levels remained normal. While the patients were receiving vitamin D/TPGS, serum vitamin E to total lipid ratio either normalized or remained normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Calcium absorption in bone disease associated with chronic cholestasis during childhood.

Fractional absorption of calcium was determined in 9 children aged 4.9 to 16.9 yr with chronic cholestatic liver disease to determine the role of calcium malabsorption in the development of metabolic bone disease. Radiological evidence of rickets was absent in all patients, but bone density, measured by single beam photon absorptiometry of the distal radius, was reduced in eight of nine subjects. Serum calcium and phosphorus concentrations were normal in all except one subject. Serum 25-hydroxyvitamin D concentration was decreased compared with controls in only one of nine patients, but serum 1,25-dihydroxyvitamin D concentrations were diminished in seven of nine subjects. In all subjects, dietary calcium and phosphorus intakes were greater than 80% of the RDA. Fractional absorption of calcium, determined by oral and intravenous administration of stable calcium isotopes, was similar in cholestatic compared with control subjects (37.1% +/- 12.5% vs. 34.0% +/- 16.4%). In the cholestatic subjects, calcium absorption correlated with serum 1,25-dihydroxyvitamin D (r = 0.871, p less than 0.002) but not 25-hydroxyvitamin D concentrations. Calcium balance, assessed by the duplicate diet method, was positive in four of five subjects. Anthropometric measurements were performed to examine the relationship between nutritional status and bone mineral content. Heights of all subjects were less than or equal to the 10th percentile and fat stores and somatic protein stores were less than the 25th percentile in six of nine subjects. We conclude that factors other than calcium malabsorption and decreased serum 25-hydroxyvitamin D concentration contribute to diminished bone mass in children with cholestatic liver disease.

Absorption↗