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S C Kalhan

Publications and source records attributed to S C Kalhan.

At least 19 recordsLinked to original sources
PubMed1992

In vivo differences between the turnover rates of leucine and leucine's ketoacid in stable cirrhosis.

Based on urinary nitrogen excretion, previous studies have indicated increased protein breakdown rates in cirrhosis. However, studies using [1-13C]-leucine infusion methodology have found normal protein breakdown rates. Because abnormal partitioning between extracellular and intracellular leucine exists in cirrhosis, plasma enrichment of leucine's keto acid (KIC), a marker of intracellular leucine, may more accurately reflect protein metabolism than plasma [1-13C]leucine enrichment. Therefore, protein breakdown and oxidation were calculated using both [1-13C]leucine and [1-13C]KIC and compared with urinary nitrogen excretion in seven cirrhotics and seven matched controls after an overnight fast. The ratio of KIC and leucine plasma enrichment was decreased (P less than 0.001) in cirrhosis because of lower KIC enrichment (P less than 0.006). Cirrhotics had increased rates of protein breakdown (P less than 0.006) and protein oxidation (P less than 0.05) based on KIC (P less than 0.006) but not leucine enrichment. In controls, protein oxidation calculated from urinary nitrogen excretion did not differ from KIC results (0.88 +/- 0.08 vs. 0.83 +/- 0.06) but was higher than the leucine method (0.88 +/- 0.08 vs. 0.73 +/- 0.05; P less than 0.01). However, in cirrhotics protein oxidation based on urinary nitrogen was lower than the KIC methodology (P less than 0.01). Therefore, cirrhotics have accelerated rates of protein breakdown and oxidation associated with increased extrarenal nitrogen loss. Furthermore, these results suggest abnormal leucine transport across cell membranes.

Adult↗
PubMed1992

Body cell mass and leucine metabolism in cirrhosis.

To investigate the influence of body composition on leucine metabolism, leucine turnover and oxidation were measured in six patients with stable biopsy-proven cirrhosis and in six age- and gender-matched controls using [1-14C]leucine tracer. Fat-free body mass and body cell mass were estimated from quantified measurements of H2(18)O and bromide dilution. Although there were no differences in body weight, body surface area, body mass index, or fat-free body mass between study groups, body cell mass was decreased in cirrhotic patients (37.6 +/- 0.1 vs. 46.4 +/- 1.8 kg; P less than 0.05). Leucine turnover did not significantly differ between groups in absolute values or when corrected for body weight or fat free body mass. However, cirrhotic patients had accelerated leucine turnover based on body cell mass (171.3 +/- 8.2 vs. 143 +/- 7.6 mumol.kg-1.h-1; P less than 0.03). Plasma leucine levels were decreased in cirrhosis (76.9 +/- 9.7 vs. 117.9 +/- 8.1 mumol/L; P less than 0.001) and correlated with an expanded extracellular water compartment (r = -0.91; P less than 0.001) and leucine oxidation (r = 0.91; P less than 0.01) in the cirrhotic patients but not in the control subjects. These data indicate that body composition and fluid compartments are important factors influencing leucine metabolism in cirrhosis and should be considered in future studies.

Adult↗
PubMed1992

Glucose, insulin, gastric inhibitory polypeptide, and pancreatic polypeptide responses to polycose during pregnancy.

Polycose, a glucose polymer produced by controlled acid enzyme hydrolysis of starch, has been proposed as an effective substitute for glucose solution in antepartum screening for glucose intolerance. The purposes of this study were to examine the glucose and hormonal responses to 50 g of glucose polymer (polycose) solution in pregnant and nonpregnant women and to compare these with the standard 50-g oral glucose challenge test. In addition, the subject's acceptance of the glucose polymer solution was evaluated. Subjects were examined after an overnight fast following a 3-day dietary preparation. There was no difference in glucose or insulin responses to glucose or polycose in either pregnant or nonpregnant women. In contrast, the gastric inhibitory polypeptide response to polycose was significantly higher than to glucose. No differences were observed in plasma pancreatic polypeptide responses to glucose and polycose. In the pregnant subjects, even though the plasma insulin response to carbohydrate challenge was higher than in the nonpregnant subjects, gastric inhibitory polypeptide levels were significantly lower. Patient satisfaction was similar with both carbohydrate solutions. These data suggest that polycose can be used as a substitute for glucose in antepartum testing, although the differences in the hormonal responses should be recognized. Further studies in a subject population with carbohydrate intolerance will be required before polycose use can be recommended in abnormal states.

Adult↗
PubMed1991

Leucine kinetics and fuel utilization during a brief fast in human pregnancy.

To examine proteolysis, protein and leucine oxidation, and fuel utilization during a brief fast (approximately 17 hours) in human pregnancy, we determined leucine kinetics, urea nitrogen excretion, and respiratory quotient (RQ) in 11 pregnant subjects during the second half of gestation, and in 11 normal nonpregnant controls. The total rate of appearance (Ra) of leucine was similar in the pregnant and control groups (pregnant 4.99 +/- 0.60 v control 5.25 +/- 1.60 mmol/h [mean +/- SD]). However, leucine Ra per kilogram was significantly lower in pregnant subjects (pregnant 68 +/- 7 v control 82 +/- 13 mumol/kg/h, P less than .01). In addition, urinary urea nitrogen excretion was also significantly less in pregnant subjects (pregnant 3.74 +/- 1.09 v control 5.58 +/- 1.6 mg/kg/h, P less than .01). The RQ measured in the pregnant group was significantly higher than controls (0.82 +/- 0.05 v 0.76 +/- 0.04, P = .01), resulting in higher calculated carbohydrate oxidation rates during fasting in pregnancy. These data suggest that total rates of proteolysis (reflected by leucine flux) are similar in pregnant and nonpregnant subjects after an overnight fast. When normalized to body weight, proteolysis is lower in pregnant subjects. Urea excretion rates are also lower in pregnancy. These findings support the hypothesis that there is a pregnancy-induced adaptation to conserve maternal protein stores during a brief fast. The higher rate of carbohydrate oxidation during fasting in pregnancy may be a reflection of the fetal-placental unit's use of glucose as its predominant oxidative substrate.

3-Hydroxybutyric Acid↗
PubMed1991

Glucose-alanine relationship in diabetes in human pregnancy.

We have previously reported a decrease in gluconeogenesis from alanine in normal pregnant women at term gestation as compared with nonpregnant women. In the present study, the effect of diabetes on alanine metabolism was examined in five gestationally diabetic (GDM) women and seven women with type I (insulin-dependent) diabetes (IDDM) during the third trimester of pregnancy. The hemoglobin A1c (HbA1c) concentrations in all subjects were within normal range, indicating good metabolic control. After an overnight fast, each subject was infused simultaneously with L-[2,3, 13C2]alanine and D-[6,6,2H2]glucose tracers as prime constant rate infusion. Plasma alanine and glucose isotopic enrichments were measured by gas chromatography-mass spectrometry. Alanine and glucose turnover rates were quantified by tracer dilution. In five subjects, the contribution of alanine carbon to CO2 was quantified by respiratory calorimetry and by measurement of 13C enrichment of expired CO2. Data from 15 previously reported normal pregnant subjects were used for comparison. The rate of alanine turnover was similar in the GDM and IDDM subjects and was not different from the normal subjects (GDM, 4.6 +/- 1.9; IDDM, 5.4 +/- 2.5; normals, 4.4 +/- 0.8 mumol/kg.min, mean +/- SD). The rate of glucose turnover was significantly reduced (P less than .05) in IDDM as compared with GDM and normal subjects (IDDM, 8.1 +/- 0.8; GDM, 11.5 +/- 3.5; normals, 12.2 +/- 2.2 mumol/kg.min). The contribution of alanine C to glucose C and expired CO2 was similar in the three groups. These data demonstrate that rigorous metabolic control results in normal glucose and alanine metabolism in diabetic pregnancy during fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Leucine kinetics during feeding in normal newborns.

To examine how leucine and protein metabolism is affected by feeding, leucine kinetics were determined in 11 normal term newborns during feeding using a prime constant tracer infusion of 1-13C leucine combined with respiratory calorimetry. Fed newborns were compared with previously studied fasting newborns. Feeding and fasting newborns had similar rates of leucine oxidation (34 +/- 3 mumol/kg/h versus 31 +/- 4 mumol/kg/h) and leucine release from existing protein (156 +/- 16 mumol/kg/h versus 164 +/- 8 mumol/kg/h). In contrast, nonoxidative disposal rates of leucine (a reflection of protein synthesis) were significantly greater in feeding newborns (170 +/- 13 mumol/kg/h versus 129 +/- 9 mumol/kg/h). A significant positive correlation between birth weight and leucine flux was demonstrated in both feeding and fasting newborns. These results suggest that 1) newborns may accomplish protein accretion primarily by increases in protein synthesis rather than suppression of protein breakdown; 2) an estimate can be made of the minimal leucine intake required to replace irreversible leucine oxidative losses (816 mumol/kg/d, 107 mg/kg/d); and 3) the positive correlation between birth weight and leucine flux in both feeding and fasting newborns may be a result of differences in previous protein and energy supplies.

Amino Acids↗
PubMed1991

Diagnosis of gestational diabetes in early pregnancy.

OBJECTIVE: To determine whether glucose intolerance can be identified early in gestation in a high-risk population so that early intervention can be planned to prevent associated morbidity. RESEARCH DESIGN AND METHODS: After appropriate dietary preparation, patients with a high risk for gestational diabetes underwent a 50-g oral glucose screening test during fasting. Patients were tested on enrollment and every 10 wk until delivery. Those with a 1-h plasma glucose value of greater than or equal to 7.5 mM underwent a 100-g oral glucose tolerance test. Gestational diabetes was based on either a markedly abnormal 50-g screening test or abnormal 100-g oral glucose tolerance test. RESULTS: Ten of 15 (66%) patients who developed gestational diabetes were diagnosed during the first half of the pregnancy. Six were diagnosed in the first trimester. If the definition of an abnormal 1-h plasma glucose value was lowered from 7.5 to 7.2 mM, an additional 2 patients could have been identified in the first trimester with an improvement in sensitivity from 70 to 91% with only a slight drop in specificity (from 91 to 88%). Diagnosis of gestational diabetes was not enhanced by measuring plasma insulin concentrations or insulin-glucose molar ratios. CONCLUSIONS: The diagnosis of gestational diabetes in a high-risk population can be made in the first half of pregnancy. Early diagnosis should permit evaluation of intervention strategies, which may result in improved perinatal outcome.

Adult↗
PubMed1991

[The early diagnosis of intestinal ischemia by gammagraphic study].

Intestinal wall necrosis without perforation was produced in six dogs. Another group of three dogs served as a control. The histologic findings, the degree of ischemia and scintigraphic images obtained after the infusions of autologous white blood cells labelled with indium-111 oxine were correlated. Positive scans were obtained in all the dogs with proven intestinal ischemia. Negative scans appeared in the dogs without ischemic insult and a false-positive scan were observed in a control dog with diarrhea.

Animals↗
PubMed1991

Measurements of total body and extracellular water in cirrhotic patients with and without ascites.

Using H2[18O] tracer isotope dilution and corrected bromide space as standard reference techniques, we determined total body water and extracellular water in cirrhotic patients with (four men and four women) and without (seven men and six women) ascites and compared them with a normal control group (eight men and six women). These results were then compared with calculations of total body and extracellular water determined by the bioelectrical impedance analysis technique. According to H2[18(O)] dilution, total body water was similar in cirrhotic patients without ascites and in controls (60.8% +/- 2.1% vs. 60.3% +/- 1.4% body wt), but was increased in patients with ascites (69.7% +/- 1.2% body wt; p less than 0.002). Correlation was excellent between the H2[18(O)] dilution and bioelectrical impedance measurements of total body water in controls and cirrhotic patients without ascites (r = 0.98; p less than 0.0001). However, this correlation was poor in cirrhotic patients with ascites (r = 0.17; not significant). According to the bromide space, extracellular water (expressed as a percentage of total body water) was increased in cirrhotic patients with (57.8% +/- 1.8%; p less than 0.001) and without (44.0% +/- 1.2%; p less than 0.001) ascites compared with controls (36.6% +/- 1.0%). A poor correlation (r = 0.41; p less than 0.13) was seen for extracellular water measurements between the bromide space method and the bioelectrical impedance method, which failed to detect the differences among the three groups observed with the bromide space technique. Furthermore, bioelectrical impedance failed to detect any change in total body or extracellular water after paracentesis, with a degree of inaccuracy that increased linearly as the amount of ascitic fluid removed increased (r = 0.97; p less than 0.001). All these intergroup comparisons remained the same, whether the analysis was of both men and women combined or for each gender individually. However, we saw differences between men and women in the control group and cirrhotic group without ascites. These results demonstrate that abnormalities in water homeostasis and compartmentalization between intracellular (the difference between total body and extracellular water fluid) and extracellular water may exist in cirrhosis whether or not fluid accumulation is clinically evident. These data further indicate that alterations in the metabolically active body cell mass (as represented by intracellular water) in cirrhosis may occur independently of total body water and calculated fat-free body mass. In addition, gender is an important variable to control for in studies of this type.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗
PubMed1990

Plasma vasoactive intestinal polypeptide in the newborn infant.

Vasoactive intestinal polypeptide (VIP) has been suggested as a possible contributor to the development of gastrointestinal problems. VIP is produced by nerve endings in the intestinal tract and appears to have marked effects on gut motility and its blood flow. Since necrotizing enterocolitis and feeding intolerance are common problems in the newborn, we examined the plasma VIP responses to feeding in healthy preterm and term newborn infants. Plasma VIP levels were measured in 20 full-term newborn infants (gestation of 39.4 +/- 0.9 weeks, mean +/- SD, and weight of 3,351 +/- 477 g) and 38 preterm infants (gestation of 27-35 weeks, weight of 920-2,440 g). In term infants, cord blood samples were obtained from the umbilical artery and vein and then before and after the feed. For preterm infants, blood samples were obtained prior to the introduction of oral feeds during the first week, and then before and after feeding once a week over the next 4 weeks. Feeding ranged from diluted premature formula to special care (24 calories per ounce) for the preterm, and breast milk or regular commercial formula for the term infants. Twenty-one healthy adults, age 25-42 years, were studied for comparison. In the term newborn infants, the plasma VIP levels in the umbilical venous blood were lower, although not statistically significant (p = 0.06), than the umbilical arterial blood (10.78 +/- 5.89 vs. 13.54 +/- 6.71 pmol/L), suggesting placental metabolism of VIP. After birth, there was a significant increase in plasma VIP levels (18.89 +/- 10.07 pmol/L, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1990

Leucine kinetics in endurance-trained humans.

This study compared whole-body leucine kinetics in endurance-trained (TRN) and sedentary (SED) control subjects. Eleven men and women (6 TRN, 5 SED) underwent a 6-h primed, constant-rate infusion of L-[1-13C]leucine. Leucine turnover and oxidation were measured using tracer dilution and by measuring 13C enrichment of expired CO2 combined with respiratory calorimetry. Whole-body leucine turnover was greater in the TRN subjects (P less than 0.004; TRN 98.3 +/- 5.0, SED 75.3 +/- 4.2 mumol.kg-1.h-1; mean +/- SE), but there was no difference between groups in leucine oxidation (TRN 13.1 +/- 0.97, SED 11.5 +/- 0.48 mumol.kg-1.h-1). Thus more leucine turnover was available for nonoxidative utilization. In addition, the TRN subjects had higher resting energy expenditures compared with the SED group, and when all subjects were included in the analysis, there was a significant correlation between energy expenditure and protein turnover (n = 11, R = 0.61, P = 0.05). Therefore the heightened resting energy expenditure in the TRN subjects may be accounted for by an increased whole-body protein turnover. These results suggest that endurance training results in increased leucine and/or protein turnover, which may contribute to the increased resting energy expenditure observed in these subjects.

Adult↗
PubMed1990

Total body water measurement in normal and diabetic pregnancy: evidence for maternal and amniotic fluid equilibrium.

The H2[18O] tracer dilution method was applied to quantify total body water in 6 normal nonpregnant women, 8 normal pregnant women (gestation 29.3 +/- 6.0 weeks, range 21-37 weeks), and 8 insulin-dependent diabetic pregnant subjects (gestation 29.4 +/- 6.1 weeks, range 20-37 weeks). Plateau or equilibrium enrichment of 18O in the breath CO2 was achieved at approximately 2 h in nonpregnant normal subjects. In contrast, in pregnant subjects equilibrium plateau was reached later, at approximately 3 h. In order to examine whether the amniotic fluid/fetal compartment had also reached equilibrium with the maternal water compartment, amniotic fluid samples were obtained from 5 women undergoing elective cesarean section, approximately 5 h after the administration of tracer H2[18O]. The 18O enrichment of amniotic fluid was similar to that of the mother. Total body water was similar in normal and diabetic pregnant subjects (40.4 +/- 4.4 vs. 40.1 +/- 5.8 kg) and represented 55.8 +/- 5.4 and 58.7 +/- 5.5% of body weight, respectively. These data demonstrate the usefulness of the H2[18O] tracer method to measure total body water in pregnancy and emphasize the importance of an adequate equilibrium period 4-5 h in order to measure the dilution of administered tracer. The measurements by H2[18O] tracer are similar to those previously reported with deuterium oxide. Insofar as total body water reflects lean body mass, the data suggest that body compositional changes in normal and diabetic pregnancy are qualitatively similar.

Adult↗
PubMed1989

Meconium aspiration syndrome: intrapartum and neonatal attributes.

To identify the fetus and newborn at risk for meconium aspiration syndrome the perinatal characteristics of 238 infants delivered through meconium-stained amniotic fluid were prospectively examined. All infants with meconium-stained amniotic fluid were routinely suctioned with a DeLee apparatus before tracheal intubation and suctioning. The type and presence of meconium in the trachea, neonatal breathing before intubation, and Apgar scores were recorded in the delivery room. Intrapartum fetal monitoring data were collected for 80% (190/238) of the mothers and umbilical artery pH for 74% (177/238) of the newborns. Despite suctioning with a DeLee apparatus and endotracheal suctioning, meconium was present in the trachea in 87/238 (37%) and meconium aspiration syndrome developed in 22 (9.2%). A total of 73% of newborns who had meconium aspiration syndrome were delivered through thick meconium. Thick meconium, the presence of fetal tachycardia, and absence of intrapartum fetal cardiac accelerations identified the fetus at high risk for meconium aspiration syndrome. The presence of these monitoring findings and thick meconium should alert obstetricians to the possibility of a fetus that requires intervention. Low umbilical artery pH, Apgar scores less than 5, and meconium in the trachea further characterized the newborn at high risk for meconium aspiration syndrome. The combination of these findings may best identify the infant delivered through meconium-stained amniotic fluid who requires close observation for meconium aspiration syndrome.

Amniotic Fluid↗
PubMed1989

Urea synthesis, nitrogen balance, and glucose turnover in growth-hormone-deficient children before and after growth hormone administration.

We measured the effect of human growth hormone (hGH) on urea synthesis, nitrogen retention, and glucose turnover in ten euthyroid growth hormone (GH)-deficient children before and after seven daily injections of 0.1 U/kg hGH. The patients were fed a weight-maintaining diet with 9% of energy derived from protein. Following an overnight fast, urea synthesis and glucose turnover were determined using a primed constant infusion of [15N2] urea and a constant infusion of [6,6-2H2] glucose. Human growth hormone produced a decrease in urea nitrogen synthesis from 6.8 +/- 0.5 to 4.2 +/- 0.4 mg/kg.h; (P less than .01), while plasma urea nitrogen decreased from 13.1 +/- 0.8 to 7.4 +/- 0.8 mg/dL; (P less than .01). The decrease in urea synthesis was reflected in a corresponding decrease in urine urea nitrogen excretion (-2.8 mg/kg.h). There was a significant correlation between plasma urea nitrogen and urea synthesis rate both before (r = 0.85, P less than .01) and after (r = 0.79, P less than .01) hGH treatment. In response to hGH, there was a rise in both plasma glucose (81.4 +/- 2.2 v 89.8 +/- 2.3 mg/dL; P less than .05) and insulin (5.7 +/- 0.8 v 13.1 +/- 3.0 microU/mL; P less than .05), however, glucose turnover remained unchanged (4.7 +/- 0.3 v 4.6 +/- 0.6 mg/kg.min). After seven days of growth hormone treatment, the patients were placed on 0.1 U/kg of hGH three times a week for 6 months, and their growth rate was calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1989

Beta-adrenergic blockade alters whole-body leucine metabolism in humans.

This study examined the effects of a nonselective beta-blocking agent on whole-body leucine metabolism in humans. Five normal, healthy subjects (4 male, 1 female) underwent a 6-h primed, constant-rate infusion of L-[1-13C]leucine after 5 days of twice daily oral use of 80 mg propranolol and a placebo. Leucine turnover was determined by tracer dilution and leucine oxidation by 13C enrichment of the expired CO2. Propranolol decreased the total daily energy expenditure from 1,945 +/- 177.5 to 1,619 +/- 92.5 kcal/day (P less than 0.05). A fasting associated decrease in blood glucose and an attenuated rise in free fatty acids and ketones were observed during beta-blockade. Propranolol also increased plasma leucine concentrations (73.1 +/- 8.7 to 103.4 +/- 7.3 mumol/l; P less than 0.05) and leucine oxidation (13.2 +/- 1.2 to 17.1 +/- 1.3 mumol.kg-1.h-1; P less than 0.05), although leucine turnover was not significantly altered (100.5 +/- 7.3 vs. 126.0 +/- 12.3 mumol.kg-1.h-1). In addition, the urinary urea nitrogen-to-creatinine ratio was greater during propranolol administration (0.24 +/- 0.04 vs. 0.34 +/- 0.02 mol/g; P less than 0.05). These data suggest that the beta-adrenergic system plays a role in the modulation of whole-body leucine metabolism in humans. Whether these changes are the result of a direct effect on skeletal muscle or an indirect effect mediated by altering the fuel supply to skeletal muscle cannot be discriminated by the present study.

Adult↗