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Biomedical subjects

E F Bell

Publications and source records attributed to E F Bell.

At least 19 recordsLinked to original sources

Incidence of vocal fold paralysis in infants undergoing ligation of patent ductus arteriosus.

BACKGROUND: Left-sided, iatrogenic vocal fold paralysis (IVFP) secondary to recurrent laryngeal nerve injury is a potential complication of ligation of patent ductus arteriosus (PDA). This study investigates specific risk factors associated with IVFP. METHODS: A retrospective chart review was performed for all infants 12 months of age or younger who underwent operative PDA closure at the University of Iowa from January 1, 1991, to January 1, 1994. RESULTS: Six cases of IVFP were diagnosed in 68 infants who underwent PDA ligation using clips (52.9%), suture ligatures (41.2%) or both (5.9%). Compared with infants without postoperative IVFP, infants with IVFP were smaller at birth (0.9 versus 2.3 kg; p < 0.001) and more premature (gestational age, 26.3 versus 33.8 weeks; p < 0.001), and were smaller (1.1 versus 3.4 kg; p < 0.001) and younger (31.9 versus 88.4 days; p < 0.001) at operation. Weight gain from birth to operation was significant only in infants without postoperative IVFP (p < 0.05). Although the overall incidence of IVFP in all infants undergoing PDA closure was 8.8%, five of the six cases (83.3%) of IVFP occurred in extremely low birth weight infants, ie, those weighing 1 kg or less at birth. Among the cohort of extremely low birth weight babies undergoing operation, the incidence of IVFP was 22.7%. Iatrogenic vocal fold paralysis was associated only with the use of surgical clips; however, because clips were used in 90.9% of the premature infants requiring PDA ligation, it was not possible to establish whether suture ligature is a safer technique. CONCLUSIONS: This study demonstrates that the single major risk factor for IVFP after ligation of PDA is birth weight less than 1 kg.

Birth Weight

Duplex Doppler sonography of changes in portal vein flow in healthy term newborn infants after feeding.

To establish reference values for changes in portal venous diameter, angle- corrected maximal flow velocity, and flow in healthy term newborn infants after formula feeding, we studied 20 subjects using duplex Doppler sonography. After feeding, portal venous diameter increased from 3.6 +/- 0.1 (mean +/- standard error of the mean) to 3.9 +/- 0.1 mm at 15 min and decreased to 3.8 +/- 0.1 at 60 min. Maximal flow velocity increased from 24.1 +/- 1.3 cm/s to a maximum of 35.9 +/- 2.4 cm/s at 15 min and decreased to 28.8 +/- 1.5 cm/s at 60 min. Flow increased from 85.0 +/- 7.5 ml/min to a maximum of 153.6 +/- 14.9 ml/min at 15 min with decrease similar to the maximal flow velocity curve. We conclude that formula feeding produces peak portal blood flows of nearly twice the fasting values at 15 min after feeding and returns almost to fasting value by 60 min.

Eating

Diet and body composition of preterm infants.

There have been few systematic studies of the effects of energy and protein intake on the body composition of preterm infants. Analysis of published studies suggests a roughly inverse relation between energy stored per gram of weight gain (a measure of the fatness of new tissues) and the ratio of protein to energy in the preterm infant's diet. At least within a certain range of energy and protein intakes, a higher protein diet promotes leaner body composition. Studies of the effects of varying the dietary ratio of carbohydrate to fat in preterm infants have shown reduced rates of carbon dioxide production with high-fat diets, fed by either the parenteral or enteral route. The little information available suggests no clear effect of varying the carbohydrate-to-fat ratio on body composition. The mineral content of the body can be influenced by diet. Insufficient intakes of calcium and phosphorus reduce the bone mineral content and thus the whole-body content of these minerals.

Body Composition

A gradient-layer calorimeter for measurement of energy expenditure of infants.

We have developed and validated a gradient-layer calorimeter for direct measurement of energy expenditure of preterm infants. Infant calorimeters must be operated and tested differently from adult calorimeters, because the calorimeter must be warmed during operation to limit heat loss from the infant, the calorimeter wall temperature (which is selected on the basis of the infant's maturity) must be precisely controlled, and energy expenditure (heat output) is typically < 10 W. We calibrated our calorimeter by varying the heat produced by a dry source (manikin or light bulb) with airflow (n = 42) and without airflow (n = 8) at various water jacket temperatures (n = 7) and by a wet source (combustion of ethyl alcohol) with airflow (n = 9). With no air moving, qc = 0.740 Vc + 0.029 Twj-0.697, where qc (W) is the estimated output of the heat source measured by the calorimeter, Vc (mV) is the gradient-layer voltage of the calorimeter, and Twj (degree C) is the temperature of the water jacket surrounding the walls of the device. From this equation and enthalpy calculations, the slope and intercept of the regression line relating the estimated heat production to the actual heat produced from alcohol combustion are 1.029 +/- 0.046 and -0.549 +/- 0.484 (SE), respectively. The slope is not significantly different from unity, and the intercept is not significantly different from zero. Thus we can accurately estimate the energy expenditure of preterm infants from the equations describing our calorimeter, and we can accurately resolve the total heat output into a dry (nonevaporative) component and a wet (evaporative) component.

Calibration

Effect of intravenous amino acids on protein metabolism of preterm infants during the first three days of life.

Twenty-three preterm infants with respiratory distress syndrome (mean birth weight 1.07 kg, SD 0.24 kg) were randomly assigned to receive glucose alone or glucose with amino acids (1.5 g.kg-1.d-1) i.v. beginning on the 1st d of life. Blood ammonia and serum urea, CO2 content, sodium, potassium, chloride, and ionized calcium concentrations were normal and did not differ between treatment groups. Nitrogen balance was significantly greater in the group that received amino acids [88 (SD 54) versus -135 (SD 45) mg.kg-1.d-1]. In 12 infants (seven, glucose-only; five, glucose and amino acids), leucine kinetic studies were also performed on the 3rd d of life. These 12 infants received a 4-h primed constant infusion of L-[1-13C]leucine. Blood and breath were collected and analyzed for [1-13C]ketoisocaproate and 13CO2, respectively. Leucine turnover and oxidation were calculated. Both leucine turnover and oxidation were significantly higher in the group receiving amino acids than in the glucose-only group [241 (SD 38) versus 164 (SD 25) mumol.kg-1.h-1 and 71 (SD 22) versus 40 (SD 17) mumol.kg-1.h-1, respectively]. In addition, the calculated rate of protein synthesis was higher in the group receiving amino acids [6.9 (SD 1.1) versus 5.0 (SD 1.2) g.kg-1.d-1]. These data indicate that the i.v. administration of amino acids (1.5 g.kg-1.d-1) to ill preterm infants beginning on the 1st d of life improves whole-body protein balance as a result of increased protein synthesis.

Amino Acids

Addition of metolazone to overcome tolerance to furosemide in infants with bronchopulmonary dysplasia.

A decreased response to the loop diuretic furosemide develops within a few doses in young infants. We tested the hypothesis that the use of the thiazide-like diuretic metolazone, in combination with furosemide, would inhibit water and electrolyte reabsorption and overcome pharmacologic tolerance to furosemide alone. Infants with bronchopulmonary dysplasia of similar gestational and postnatal ages were randomly assigned to one of three groups. Group 1 (n = 6) received furosemide (1 mg/kg per dose) intravenously every 24 hours for a total of five doses. Group 2 (n = 8) received the same treatment as group 1, but in addition metolazone (0.2 mg/kg per dose) was given enterally with doses 3 and 4 of furosemide. Group 3 (n = 8) received metolazone (0.2 mg/kg per dose) enterally every 24 hours for five doses. Urine was collected before the first diuretic dose and throughout the study for determination of the urine flow rate; urinary excretion of sodium, chloride, and potassium; and creatinine clearance. Urinary flow rate and urinary sodium and chloride excretion increased after the first dose in all groups. In the infants treated with either furosemide or metolazone, urinary flow rate and urinary and chloride excretion returned to baseline values after the last three doses. In contrast, when furosemide was administered with metolazone, urinary flow rate and urinary excretion of sodium, chloride, and potassium were greater than the values for baseline and for the previous dose, as well as for the corresponding doses of furosemide in group 1 and metolazone in group 3. Tolerance to furosemide (group 1) and metolazone (group 3) appeared to be explained by compensatory increased sodium and chloride reabsorption without changes in creatinine clearance. We conclude that the administration of metolazone with furosemide enhances diuresis, natriuresis, and chloruresis and overcomes the rapid development of tolerance to furosemide in infants with bronchopulmonary dysplasia by blocking the compensatory increase in renal sodium and chloride absorption.

Bronchopulmonary Dysplasia

Plasma amino acid concentrations and amino acid ratios in normal adults and adults heterozygous for phenylketonuria ingesting a hamburger and milk shake meal.

Plasma amino acid concentrations were measured and selected amino acid ratios were calculated in 12 normal adults and 12 adults heterozygous for phenylketonuria (PKU) ingesting a hamburger and milk shake meal providing 1 g protein/kg body wt. Plasma concentrations of all amino acids increased significantly over baseline after meal ingestion in both groups, reaching the highest mean values 3-5 h after meal ingestion. Plasma phenylalanine concentrations were significantly higher in heterozygous than in normal subjects both before and at all times after meal ingestion. The absolute increase in plasma phenylalanine concentration over baseline and the area under the plasma phenylalanine concentration-time curve were approximately twice as large in heterozygous as in normal subjects. However, the molar ratio of the plasma phenylalanine concentration to the sum of the plasma concentrations of the other large neutral amino acids did not increase significantly over baseline, but rather decreased.

Amino Acids

Infrared thermometry of newborn infants.

An infrared thermometer, the FirstTemp, was tested among newborn infants by comparing tympanic membrane temperature measurements in three operating modes, "Cal-tympanic," "Cal-surface," and "Cor-tympanic," with nearly simultaneous tympanic membrane, rectal, and axillary temperature measurements using other standard methods. The FirstTemp underestimated other measurements of body temperature in the "Cal-tympanic" mode and overestimated them in the "Cor-tympanic" mode. In the "Cal-surface" mode, the First-Temp readings were significantly lower than tympanic membrane temperatures measured with a thermistor probe and electronic thermometer (mean difference 0.2 degrees C) but not significantly different from rectal or axillary temperatures. According to these results, the FirstTemp can be used reliably in the "Cal-surface" mode but not in the "Cal-tympanic" or "Cor-tympanic" mode. Its speed and ease of operation offer significant advantages over traditional clinical methods of temperature measurement.

Axilla

Variability of abdominal circumference of premature infants.

Serial measurements of abdominal circumference were made in 27 premature infants 1 hour before feeding, immediately before and after feeding, and 1 and 2 hours after feeding. In some infants these measurements were repeated for 2 (n = 18) or 3 (n = 3) consecutive days. All 258 measurements were performed by the same examiner; 124 were also repeated blindly by another examiner to test interobserver reliability. The coefficient of variation of repeated measurements of any one infant by the same examiner on a single day was 2.7%. Ninety percent of repeated measurements agreed within 1.5 cm. The interobserver reliability was 0.99. Abdominal circumference was positively correlated with birth weight (P = .0001) and time from last defecation (P = .0001) and negatively correlated with time from last feeding (P = .04). Increases in abdominal circumference of less than 1.5 cm occur normally and, in the absence of other clinical signs, should not be considered indicative of disease.

Abdomen

Repeated ingestion of aspartame-sweetened beverages: further observations in individuals heterozygous for phenylketonuria.

Six adults heterozygous for phenylketonuria (PKU) ingested eight successive servings of unsweetened and aspartame (APM)-sweetened beverage at 1-hour intervals in a randomized, balanced, crossover design. In one part, the eight beverage servings were not sweetened. In the other, each of the eight beverage servings provided 600 mg of APM, a dose equivalent to the amount provided by 36 oz of an APM-sweetened diet beverage. Plasma aspartate concentration was not significantly increased after ingestion of unsweetened or APM-sweetened beverage. Similarly, ingestion of the unsweetened beverage had no significant effect on plasma phenylalanine concentration. However, ingestion of APM-sweetened beverage significantly increased plasma phenylalanine concentrations 2.35 to 4.03 mumol/dL above baseline 30 minutes after ingestion. Plasma phenylalanine values reached a steady-state after administration of five servings of APM-sweetened beverage and were slightly, but significantly higher than usual postprandial values for adults heterozygous for PKU. Similarly, the ratio of the plasma phenylalanine concentration to the sum of the concentration of the large neutral amino acids was significantly higher than usual postprandial values. Blood methanol and formate concentrations remained within normal limits. These data indicate that a fasting adult heterozygous for PKU could consume the equivalent of 24 12-oz servings of APM-sweetened beverage over an 8-hour period and only increase plasma phenylalanine concentration to a modest degree.

Adult

Aspartame ingestion with and without carbohydrate in phenylketonuric and normal subjects: effect on plasma concentrations of amino acids, glucose, and insulin.

Seven subjects homozygous for phenylketonuria (PKU) and seven normal subjects were administered four beverage regimens after an overnight fast: unsweetened beverage, beverage providing carbohydrate (CHO), beverage providing aspartame (APM), and beverage providing APM plus CHO. The APM dose (200 mg) was the amount provided in 12 oz of diet beverage; the CHO was partially hydrolyzed starch (60 g). Plasma amino acid concentrations were determined after dosing and the molar plasma phenylalanine (Phe) to large neutral amino acid (LNAA) ratio calculated. APM administration without CHO did not increase plasma Phe concentrations over baseline values in either normal or PKU subjects (5.48 +/- 0.85 and 150 +/- 23.0 mumols/dL, respectively). Similarly, the Phe/LNAA did not increase significantly. Ingestion of beverage providing APM and CHO did not significantly increase plasma Phe concentrations over baseline values in either normal or PKU subjects. However, ingestion of beverage providing CHO (with or without APM) significantly decreased plasma levels of valine, isoleucine, and leucine 1.5 to 4 hours after dosing in both normal and PKU subjects, thereby increasing the Phe/LNAA ratio significantly. These data indicate that changes noted in Phe/LNAA values after ingestion of beverage providing APM plus CHO were due to CHO. The plasma insulin response to beverage providing CHO (with or without APM) was significantly higher in PKU subjects than in normals.

Adolescent

Effect of sucrose on the metabolic disposition of aspartame.

Twelve normal adult subjects ingested a beverage providing 0.136 mmol aspartame/kg body wt on 2 different days. On 1 study day the beverage provided only aspartame, on the other the beverage provided both aspartame and 3.51 mmol sucrose/kg body wt. The high mean plasma phenylalanine concentrations were similar after administration of aspartame alone (158 +/- 28.9 mumol/L, mean +/- SD) and administration of aspartame plus sucrose (134 +/- 44.1 mumol/L). Evaluation of the area under the plasma concentration-time curve (AUC) for phenylalanine also showed no significant difference between groups (197 +/- 49.1 vs 182 +/- 28.3 mumol.L-1.h for aspartame alone and aspartame plus sucrose, respectively). Similarly, the high mean ratio of phenylalanine to large neutral amino acids (Phe:LNAA) in plasma did not differ significantly (0.265 +/- 0.046 for aspartame alone, 0.275 +/- 0.107 for aspartame plus sucrose). However, there was a small but significant difference between groups for the 4-h AUC values for plasma Phe:LNAA. The simultaneous ingestion of sucrose with aspartame had only minor effects on aspartame's metabolic disposition.

Adult

Effect of repeated ingestion of aspartame-sweetened beverage on plasma amino acid, blood methanol, and blood formate concentrations in normal adults.

Aspartame (APM) is a widely used dipeptide sweetener (L-aspartyl-L-phenylalanine methyl ester). It has been suggested that excessive use of APM might elevate plasma aspartate, phenylalanine, and/or methanol concentrations to levels that are potentially harmful. Six normal young adults ingested eight successive servings of unsweetened and APM-sweetened beverage at one-hour intervals in a balanced crossover design. In one part, the beverage was not sweetened. In the other, each serving of beverage provided 600 mg APM, a dose equivalent to the amount provided by 36 oz of APM-sweetened diet beverage. Plasma aspartate concentration was not significantly increased after ingestion of unsweetened or APM-sweetened beverage. Similarly, ingestion of the unsweetened beverage had no significant effect on plasma phenylalanine concentration. However, ingestion of APM-sweetened beverage significantly increased plasma phenylalanine levels 1.41 to 2.35 mumol/dL above baseline 30 minutes after ingestion. Plasma phenylalanine values reached a steady state after administration of four to five servings and did not exceed normal postprandial values at any time. Blood methanol and formate concentrations remained within normal limits. The data indicate ready metabolism of APM when administered at levels that may be ingested by normal individuals who are heavy users of diet beverages.

Adult

Repeated ingestion of aspartame-sweetened beverage: effect on plasma amino acid concentrations in individuals heterozygous for phenylketonuria.

It has been suggested that excessive use of aspartame (APM) (N-L-alpha-aspartyl-L-phenylalanine methyl ester) might grossly elevate plasma aspartate and phenylalanine concentrations in individuals heterozygous for phenylketonuria (PKUH). In study 1 six adult PKUH (three males; three females) ingested three successive 12-oz servings of beverage at 2-h intervals. The study was carried out in two parts in a randomized crossover design. In one arm the beverage was not sweetened. In the other the beverage provided 10 mg APM/kg body weight per serving. The addition of APM to the beverage did not significantly increase plasma aspartate concentration but did increase plasma phenylalanine levels 2.3 to 4.1 mumol/dL above baseline values 30 to 45 min after each dose. The high mean plasma phenylalanine level after repeated APM dosing (13.9 +/- 2.15 mumol/dL) was slightly, but not significantly, above the normal postprandial range for PKUH (12.6 +/- 2.11 mumol/dL). In study 2 six different adult PKUH ingested beverage providing 30 mg APM/kg body weight as a single bolus. The high mean plasma phenylalanine concentration and the phenylalanine to large neutral amino acid ratio were significantly higher when APM was ingested as a single bolus than when ingested as a divided dose.

Adult

Upper limit of vitamin E in infant formulas.

Reports of toxicity to enterally administered vitamin E are rare in infants. However, increased risks of sepsis and necrotizing enterocolitis have been reported after both enteral and parenteral vitamin E, primarily when plasma (or serum) vitamin E levels exceed 3.5 mg/dl. Levels this high are seldom seen with enteral vitamin E when intake is 25 mg d-alpha-tocopherol equivalent/(kg.d) or less. Intakes below this threshold will be provided by infant formulas with vitamin E to energy ratios of up to 20 mg/100 kcal (30 IU/100 kcal) so long as energy intake does not exceed 125 kcal/(kg.d). To allow a margin of safety, it would be reasonable to limit the amount of vitamin E added to the formula during its manufacture to half this amount, or 10 mg/100 kcal (15 IU/100 kcal). This level coincides with the highest levels of vitamin E found in human colostrum and is 20 times the recommended lower limit for vitamin E in infant formula of 0.5 mg/100 kcal.

Adult

Effects of furosemide on body water compartments in infants with bronchopulmonary dysplasia.

We studied the effects of a single dose of intravenous furosemide on the body water compartments of nine infants with bronchopulmonary dysplasia. We measured total body water, extracellular water, and plasma volume using deuterium oxide, sodium bromide, and Evans blue dye, respectively. From the results of these measurements, we calculated cell water, interstitial water, red cell volume, and total blood volume. We performed these measurements on the first day of the study and again 28 h later, 4 h after an intravenous dose of furosemide (1 mg/kg). All infants had a brisk diuresis in the first hour after the dose, but urine output was no greater during the 24-h period after the dose than during the preceding 24-h period. Total body water, extracellular water, and interstitial water were significantly decreased 4 h after furosemide. There was no change in plasma volume, red cell volume, or total blood volume.

Body Fluid Compartments