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T Jaksic

Publications and source records attributed to T Jaksic.

At least 37 records · Page 2Linked to original sources

Integration of amino acid and carbon intermediary metabolism: studies with uniformly labeled tracers and mass isotopomer analysis.

The central pathways of metabolism include glycolysis and gluconeogenesis, fatty acid synthesis and beta-oxidation, the citric acid cycle and ureagenesis. Because these pathways intersect, changes in one pathway, due to inborn error or disease, affect pathways that may seem remote from the initial metabolic defect. These metabolic interrelationships also present difficulties for isotopic studies, because once carbon derived from isotopic tracers is introduced into metabolism it is extensively recycled. The use of multiple labeled (especially uniformly 13C-labeled ([U-13C]), metabolic tracers, in conjunction with mass isotopomer distribution analysis of mass and nuclear magnetic spectra, has enabled the development of methods that resolve some of these difficulties. Suitable choices of tracers and analytes allow the simultaneous measurement of multiple pathways and, importantly, their kinetic interrelationships. We illustrate three uses of the technique: (1) the unequivocal determination of trace fluxes; (2) the quantification of biosynthetic pathways: and (3) the dissection, in vivo, of the citric acid (Krebs) cycle. In each case, different combinations of [U-13C]tracer and metabolic end product have revealed metabolic phenomena that otherwise would remain unidentified. A particularly striking, and unexpected, observation that has emerged from recent studies using the technique, suggests that the key dehydrogenase reactions in the Krebs cycle may be reversible. Although this approach is of relatively recent development, it has already given a number of novel insights into the organization of the central metabolic pathways. It should provide a powerful method of investigating the metabolic impact of genetic disease and provide invaluable support of the assessment of new therapeutic interventions.

Amino Acids↗

Importance of diarrhea as a presenting symptom of appendicitis in very young children.

BACKGROUND: Appendicitis is an uncommon diagnosis in very young children. It is frequently complicated by delays in diagnosis, perforation, and lengthy hospital stays. OBJECTIVES: To review our recent experience with appendicitis among children younger than 3 years old, and to identify the independent predictors of a prolonged hospital stay. METHODS: A retrospective case series review was performed on all children under age 3 who had an appendectomy for appendicitis between January 1983 and February 1994. Multiple regression analysis was used to identify the independent predictors of a prolonged hospital stay. RESULTS: Sixty-three children were identified. Mean age was 2.2 years (range 11 to 35 months). The mean delay from onset of symptoms to presentation was 4.3 days. Fifty-seven percent were initially misdiagnosed. Diarrhea was reported in 33%. Perforation and/or gangrene were found in 84%. Perforation and/or gangrene at laparotomy and a history of diarrhea at presentation were independent predictors of a prolonged hospital stay. CONCLUSIONS: Appendicitis in children under 3 years old is characterized by delays in diagnosis and perforation. A history of diarrhea is an important factor that confuses the diagnosis, prolongs the observation period, and delays appropriate therapy.

Appendectomy↗

Meta-analysis of the risk of metachronous hernia in infants and children.

BACKGROUND: Inguinal herniorrhaphy is the most common general surgical procedure performed in children. The presence of a contralateral patent processus vaginalis forms the basis of the recommendation for contralateral exploration in patients undergoing unilateral herniorrhaphy. However, a patent processus vaginalis does not necessarily go on to become a clinically apparent inguinal hernia. METHODS: All published pediatric series, in which patients underwent unilateral inguinal hernia repair and were evaluated for the development of a metachronous hernia, were included. The incidence of and risk factors associated with development a metachronous hernia were evaluated with meta-analysis. RESULTS: There were 15,310 patients ranging in age from birth to 16 years, including premature infants. Of these, 1,062 patients (7%) developed a metachronous hernia. Gender and age were not risk factors. There was an 11% risk of metachronous hernia if the original hernia was on the left side, a risk that was 50% greater than if the original hernia was on the right. Of patients who developed a metachronous hernia, 90% did so within 5 years. The complication rate of metachronous hernia was 0.5%. CONCLUSION: There is no role for routine contralateral groin exploration. High-risk infants and children, especially those who undergo left inguinal herniorrhaphy, may benefit from contralateral groin exploration. If a patent processus vaginalis is found, it should be ligated. Patients who do not undergo contralateral groin exploration should be followed up for 5 years.

Adolescent↗

Stable isotopic quantitation of protein metabolism and energy expenditure in neonates on- and post-extracorporeal life support.

It is generally assumed that extracorporeal life support (ECLS) provides a metabolic "rest state" by replacing approximately 80% of cardiopulmonary work. The aim of this study was to precisely quantify neonatal energy expenditure (EE) and whole-body protein metabolism on (during) and post (after) venoarterial ECLS using stable isotope tracer techniques. Nine parenterally fed neonates on-ECLS were studied at 7.8 +/- 1.0 days of life (mean +/- SE), five of which were studied post-ECLS on 27.0 +/- 5.4 days of life. EE and whole-body protein metabolism were quantified using a primed, continuous infusion of L-[1-(13)C]leucine and NaH13CO3. The neonates studied on- and post-ECLS had similar rates of endogenous leucine flux (370 +/- 46 micromol/kg/h v 339 +/- 76 micromol/kg/h), leucine oxidation (161 +/- 22 micromol/kg/h v 121 +/- 25 micromol/kg/h), nonoxidative disposal rates of leucine (313 +/- 37 micromol/kg/h v 331 +/- 75 micromol/kg/h), net protein balance (-2.31 +/- 0.8 g/kg/d v -0.33 +/- 1.1 g/kg/d), and EE (88.6 +/- 7.7 kcal/kg/d v 84.3 +/- 9.2 kcal/kg/d). These results demonstrate that neonates on-ECLS are in hypermetabolic and protein catabolic states that continue in the post-ECLS phase. The authors conclude that ECLS does not provide a metabolic "rest state."

Carbon Dioxide↗

Does extracorporeal membrane oxygenation benefit neonates with congenital diaphragmatic hernia? Application of a predictive equation.

The overall survival of neonates with congenital diaphragmatic hernia (CDH) remains poor despite the advent of extracorporeal membrane oxygenation (ECMO). Attempts at accurately predicting survival have been largely unsuccessful. The purpose of this study was twofold: (1) to identify independent predictors of survival from a cohort of CDH neonates treated at the authors' institution when ECMO was not available and combine them to form a predictive equation, and (2) to apply the equation prospectively in a cohort of CDH neonates, treated at the same institution when ECMO was available, to determine whether ECMO improves outcome. From the clinical data of 62 CDH neonates treated at the authors' center by the same team of university neonatologists and pediatric surgeons between 1983 and 1993 (before ECMO availability), 15 preoperative and seven operative variables were selected as potential independent predictors. When subjected to multivariate, stepwise logistic regression analysis, four variables were identified as statistically significant (P < .05), independent predictors of survival: (1) ventilatory index (VI), (2) best preoperative PaCO2, (3) birth weight (BW), and (4) Apgar score at 5 minutes. When combined via logistic regression analysis, the following predictive equation was formulated: P (probability of survival to discharge) = [1 + e(x)]-1 where x = 4.9 - 0.68 (Apgar) - 0.0032 (BW) + 0.0063 (VI) + 0.063 (PaCO2). Applying a standard cut-off rate of survival at less than 20%, the equation yielded a sensitivity of 94% and a specificity of 82% in identifying the correct outcome of patients treated with conventional ventilatory management. The overall survival rate was 66%. Since the availability of ECMO at the center, 32 CDH neonates were treated using the same conventional ventilatory treatment and surgical repair by the same university staff. The overall survival rate was 69%. The predictive equation was applied prospectively to all neonates to determine predicted outcome, but was not used to decide the treatment method. Eighteen neonates received conventional therapy alone; 16 of 18 survived (89%). Fifteen of the 16 patients who survived had their outcomes predicted correctly (94%). Fourteen neonates did not respond to conventional therapy and required ECMO; 6 of 14 survived (43%). Six of the eight patients predicted to survive, lived (75%). All six patients predicted to die, died despite the addition of ECMO therapy (100%). The mean hospital cost, per ECMO patient who died, was $277,264.75 +/- $59,500.71 (SE). An odds ratio analysis, using the four independent predictors to standardize for degree of illness, was performed to assess the risk associated with adding ECMO therapy. The result was 1.25 (P = 0.75). Although the cohort was not large enough to eliminate significant beta error, the data strongly suggested no advantage of ECMO. At this center, absolute survival rates for neonates with CDH have not been significantly altered since ECMO has become available (66% v 69%). The authors conclude that the predictive equation remains an accurate measurement of survival at their center even when ECMO is used as a salvage therapy. The method of creating a predictive equation may be applied at any institution to determine the potential outcome of CDH neonates and assess the effect of ECMO, or other salvage therapies, on survival rates.

Decision Support Techniques↗

Glucose production and gluconeogenesis are negatively related to body weight in mechanically ventilated, very low birth weight neonates.

The regulation of gluconeogenesis by low birth weight infants remains poorly delineated. To investigate this, 15 5-d-old infants (26-31-wk gestational age, 795-1485-g body weight), were infused i.v. for 4 h with uniformly labeled [U-13C]glucose (5 mg/kg/min) as the sole source of glucose. Intralipid (3 mg/kg/ min) was provided, but no amino acids were given. Blood samples were taken immediately before and after 4 h of tracer infusion. The isotopic enrichments of plasma glucose and alanine were measured by selected ion monitoring gas chromatography mass spectrometry. Glucose production rates were calculated from the isotopic dilution of plasma [U-13C]glucose and the glucose infusion rate. Gluconeogenesis was estimated from the relative isotopic enrichments of [M + 3]- and [M + 6]-glucose, using the isotopic enrichment of plasma [U-13C]alanine, to define the isotopic dilution of the 3-carbon pool, and previously published equations to calculate the isotopic dilution of hepatic oxaloacetate. Glucose production (15 +/- 9 mumol/kg/min) was negatively related to body weight (r = -0.67; p < 0.05) and the ratio of the isotopic enrichments of [13C3]alanine:[13C6]glucose (0.27 +/- 0.07) was positively related to body weight (r = 0.74; p < 0.025). Both relationships were exponential. Gluconeogenesis (via pyruvate) accounted for 72 +/- 28% of glucose production, and gluconeogenesis per unit body weight was negatively and exponentially (r = -0.82; p < 0.005) related to body weight. These results demonstrate that neonates whose birth weights are less than 1200 g have a particularly high glucose production rate secondary to enhanced gluconeogenesis. We speculate that these results reflect a high weight-specific glucose demand that is met by up-regulation of gluconeogenesis.

Body Weight↗

Compartmentation of endogenously synthesized amino acids in neonates.

The conversion of D-[U-13C]glucose to proline (Pro), aspartate (Asp), and cysteine (Cys) is limited in premature neonates, implying that these amino acids (AA) are conditionally essential. This study was performed to determine whether these findings resulted from an insufficient precursor dose or intracellular compartmentation of newly synthesized amino acids, rather than inadequate synthesis. In the first phase of this study, seven total parenteral nutrition-fed, premature neonates received IV D-[U-13C]glucose at 5 mg/kg/min for 4 hr. In the second phase, a separate cohort of eight patients received an identical infusion. Blood was obtained before and at the end of the infusion. Isotopic enrichments of the free plasma AA and glucose were measured using gas chromatography/mass spectrometry in both studies. In phase 2, the isotopic enrichments of the AA bound to the hepatically synthesized proteins, fibrinogen and VLDL-apolipoprotein B-100 (apo B-100), were measured. In phase 1, despite a glucose precursor enrichment greater than 66%, Pro, Asp, and Cys remained the least enriched of all amino acids studied (P < 0.05). Asp, but not Pro, demonstrated very high enrichments in apo B-100 (P < 0.001), reflecting distinct intracellular compartmentation. We conclude that the limited conversion Of D-[U-13C]glucose to Pro, Asp, and Cys did not result from low precursor glucose enrichment and that there is evidence of Asp compartmentation (intracellular) in premature neonates. However, the low Pro enrichment in the free plasma AA pool and the absence of intracellular Pro compartmentation suggest that Pro may be a conditionally essential AA for premature neonates.

Amino Acids↗

Is surgical ligation of a patent ductus arteriosus the preferred initial approach for the neonate with extremely low birth weight?

The optimal approach to a patent ductus arteriosus (PDA) in an extremely low birth weight (ELBW) neonate, whether initial surgical ligation or a trial of indomethacin, has not been established. The authors reviewed the records of 82 ELBW premature infants who had surgical ligation of a PDA during a 2-year period. Thirty-one received indomethacin before ligation. Bronchopulmonary dysplasia (BPD) occurred in 33% of the infants. Predictors of BPD were prolonged positive pressure ventilation, severe intraventricular hemorrhage (IVH) and lower birth weight (BW). Seventy-seven percent of the infants survived. Predictors of mortality were severe IVH, lower BW, and the occurrence of necrotizing enterocolitis (NEC). The indomethacin-treated infants had a lower incidence of NEC and IVH. Overall, 16% of the patients had perioperative morbidity, and 10% of the patients died. The study shows that a trial of indomethacin therapy is not associated with increased complications in ELBW infants with PDA.

Bronchopulmonary Dysplasia↗

Survival after aberrant right subclavian artery-esophageal fistula: case report and literature review.

Development of a fistula between an aberrant right subclavian artery and the esophagus is a rare cause of heretofore fatal hematemesis. We report the first known survivor of this devastating complication of the most common aortic arch anomaly. Intraoperative esophagogastroduodenoscopy, intraesophageal balloon tamponade, and arteriography were the keys to successful management. This lesion should be suspected in the setting of bright red, "arterial" hematemesis. Prolonged nasogastric and/or endotracheal intubation should be avoided in patients with a known aberrant right subclavian artery or other aortic arch anomaly.

Child↗

Decreased cysteine and proline synthesis in parenterally fed, premature infants.

Little is known about the amino acid (AA) biosynthetic capacity and requirements of premature infants. This study assessed the synthesis of seven biochemically nonessential AA from a universal precursor, glucose, in stable, parenterally fed, premature neonates. Seven infants (six boys, one girl) were studied at a mean age of 6.3 +/- 0.6 (SEM) days; mean gestational age was 29.7 +/- 1.3 (SEM) weeks, and mean birth weight was 1,222.8 +/- 176.5 (SEM) grams. All infants were parenterally fed a mixture of 7.5% to 12.5% dextrose and 2.2% Trophamine, with or without lipid. Mean caloric intake was 93 +/- 8.4 (SEM) kcal/kg/d, and total AA intake was standardized at 2.86 g/kg/d AA, plus supplemental cysteine (30 mg/g AA/d). Each infant received a 4-hour continuous, unprimed intravenous infusion of a stable isotope tracer of D(-)[U13C] glucose (200 mg/kg). Blood samples were obtained before and at the end of the infusion. Conversion of the glucose tracer into seven biochemically nonessential AA (cysteine [Cys], proline [Pro], aspartate [Asp], serine [Ser], glutamate [Glu], alanine [Ala], and glycine [Gly]) was assessed by measuring their isotopic enrichment in plasma, using gas chromatography/mass spectrometry (GC/MS), and expressed as mole percent excess (MPE) (mean +/- SEM). The isotopic enrichment of plasma glucose was also measured using GC/MS. Free plasma AA concentrations (mean +/- SD) were measured using an automated amino acid analyzer. Mean MPE for M + 1, M + 2 and M + 3 Cys, and for M + 1 and M + 3 Pro were not significantly different from 0; M + 2 Pro barely achieved statistical significance (P = .048).(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗

A new stable isotope tracer technique to assess human neonatal amino acid synthesis.

The amino acid (AA) synthetic ability and requirements of human infants are undefined. A stable isotope tracer technique was employed in neonates to assess conversion of uniformly labeled 13C glucose into biochemically nonessential AA (NEAA). Ten neonates (5 males, 5 females) were studied at a mean age of 7 +/- 2.0 (SEM) days. The mean gestational age was 35.5 +/- 1.1 weeks, and the mean weight at time of study was 2,191 +/- 181 g. Six infants were fed enterally, and four received only intravenous 10% dextrose (D10W). Blood samples were obtained before, and 30, 60, and 120 minutes after an orogastric bolus of D-[U-13C]glucose (100 mg/kg). The conversion of glucose carbon into seven NEAA was assessed by measuring their isotopic enrichments in plasma, using gas chromatography/mass spectrometry (GC/MS), and was expressed as mole percent excess (MPE), with detectable MPE defined as > or = 0.2. The isotopic enrichment of plasma glucose also was measured using GC/MS. Free plasma AA concentrations were assayed using an automated AA analyzer and expressed in micromoles per liter. The mean glucose enrichment was 9.33 +/- 1.8 MPE (range, 5.82 to 13.48). Detectable 13C-labeling of the NEAA was observed as follows: Glu in 100% of infants; Gly, 100%; Ala, 90%; Ser, 80%; Asp, 70%; Cys, 60%; and Pro, 60%. Detectable Pro enrichment was observed in none of three premature infants on D10W. Free plasma Cys concentration was markedly lower than normal (19.8 v 86 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Thrombosis of the portal venous system after splenectomy for pediatric hematologic disease.

Splenic, portal, or mesenteric venous thrombosis after splenectomy for hematologic disease has not been reported in the pediatric literature. It is a rare complication associated with significant morbidity and mortality in adult reports. Between 1981 and 1991, 3 patients (13-year-old boy with hereditary elliptocytosis [HE], 13-year-old boy with thalassemia intermedia [TI], and 18-year-old girl with idiopathic thrombocytopenic purpura [ITP]) presented with abdominal pain, nausea, with or without fever, at 4, 11, and 13 days postsplenectomy, respectively. Abdominal Doppler ultrasound (US) and/or computed tomography (CT) showed: (1) an intraluminal filling defect with partial obstruction to flow in the right branch of the portal vein with the remaining vessels patent (HE); (2) splenic vein thrombosis with complete occlusion of the main portal vein and proximal superior mesenteric vein (TI); and (3) complete thrombosis of the splenic vein, proximal superior mesenteric vein and portal vein (including central radicles), with retrogastric collateralization (ITP). Subsequent imaging showed either complete resolution of vascular obstruction on no treatment (patient 1), or portal venous cavernomatous transformation with hepatofugal flow after 6 months of systemic anticoagulation (patients 2 and 3), and all 3 patients are currently asymptomatic. Postoperative sonographic evaluation of a consecutive series of pediatric splenectomies for hematologic disease (n = 16), was performed at a median of 51 days (range, 3 to 124). This demonstrated one case of asymptomatic left portal venous thrombosis with subsequent recanalization in the absence of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A 20-year review of pediatric pancreatic tumors.

Pancreatic tumors are rare surgical problems in infants and children. A 20-year audit (1971 to 1991) of this institution showed six patients ranging in age from 3 weeks to 16 years who were operated on for pancreatic neoplasms. Five of these tumors were malignant, bringing the reported experience to 71 cases. This series of malignancies included three solid cystic tumors, one insulin-secreting tumor, and one pancreatoblastoma. The clinical presentations varied: three had abdominal pain, one developed hypoglycemia, and one had an abdominal mass with jaundice. In five of the six patients pancreatic pathology was suspected preoperatively. All were treated primarily with pancreatic resection including one pancreatoduodenectomy. No radiotherapy or chemotherapy was used. The perioperative mortality was 0% with a morbidity of 50%. The long-term results are encouraging, with all patients alive after a mean follow-up of 7.8 years. These data suggest that aggressive surgical therapy is warranted in the management of pediatric pancreatic tumors.

Adenoma, Islet Cell↗

Management of papillary carcinoma arising in thyroglossal-duct anlage.

Cysts of the thyroglossal duct are common congenital abnormalities. They present as asymptomatic midline cervical swellings. The risk of malignant change is low; only 103 cases have been reported in the world literature, 85% of which were papillary adenocarcinomas. The appropriate treatment for this condition remains controversial. The authors describe three patients who had papillary carcinoma contained within a thyroglossal-duct rest. All were treated by cyst resection and thyroid suppression, but without thyroidectomy and radioactive thyroid ablation. Postoperatively, all patients remained disease free, with no recurrence at follow-up ranging from 10 to 29 years. Isolated papillary carcinomas arising from primitive thyroid remnants, associated with a palpably normal thyroid gland at surgery and a negative thyroid scan, can be treated adequately by excising the thyroglossal mass.

Carcinoma, Papillary↗

Proline metabolism in adult male burned patients and healthy control subjects.

Postabsorptive proline flux, oxidation, and endogenous biosynthesis were determined in five severely burned intensive-care-unit patients (mean age 27 y) and in six healthy, young-adult control subjects. Continuous primed, intravenous, 160-min, dual stable-isotope-tracer infusions of L-[1-13C]proline and L-[methyl-2H3]leucine were used in conjunction with measurement of plasma proline concentration and 24-h urinary hydroxyproline output. Burn patients, compared with normal individuals, demonstrated a doubling in proline and leucine flux (P less than 0.01 for both findings), a threefold enhancement of proline oxidation (P less than 0.05), a trend toward decreased proline synthesis, and a 37% reduction in plasma proline concentrations (P less than 0.05). Further, the injured group, unlike the control group, was in a distinct negative body proline balance, as proline oxidation greatly exceeded endogenous proline biosynthesis (P less than 0.01). These studies indicate that significant proline deficits may evolve during the postabsorptive period in severely burned patients and that an exogenous supply of proline might benefit the nitrogen economy of the traumatized patient.

Adult↗

Plasma proline kinetics and concentrations in young men in response to dietary proline deprivation.

This study examined plasma proline concentration flux, oxidation, and endogenous biosynthesis in five healthy young men given three isocaloric, isonitrogenous diets for 1 wk [a complete egg-pattern amino acid diet (diet 1), an amino acid mixture devoid of proline (diet 2), and a diet composed solely of indispensable amino acids (diet 3)]. At the end of each dietary period, a 360-min postabsorptive, primed, continuous stable-isotope-tracer infusion of L-[1-13C]proline and L-[methyl-2H3]leucine was performed in all subjects. Plasma proline concentrations declined by 22% on diet 2 (p less than 0.02) and by 29% on diet 3 (p less than 0.01). No statistically significant (p greater than 0.2) changes were observed for proline oxidation, endogenous biosynthesis, or flux. The data suggest that the absence of proline in the human diet does not trigger changes in proline dynamics during the postabsorptive state. The metabolic significance of the reduction of plasma proline concentrations requires elucidation.

Adult↗

Advances in hospital nutrition.

The General Clinical Research Center facilities have been largely responsible for expansion of knowledge in the field of hospital nutrition. Expansion of this knowledge base has led to major medical advances in this century. Without the meticulous attention necessary for metabolic balance studies many if not most of these advances would have been seriously delayed. The role that General Clinical Research Centers have played and will continue to play cannot be overestimated.

Enteral Nutrition↗

Resting energy expenditure in the critically ill: estimations versus measurement.

A prospective trial was conducted in 20 surgical intensive care unit patients receiving mechanical ventilation to compare estimates of resting energy expenditure (REE) with the measured values. The 12 women and 8 men (mean age 61.7 +/- 2.8 (s.e.m.) years) underwent a full nutritional assessment before measurement of their REE by indirect calorimetry using the MGM II metabolic cart (Utah Medical). Their REE was estimated by the Harris-Benedict formula (mean 1324 +/- 53 (s.e.m.) kcal/day) as well as an empirical formula (where empirical formula = 22 x body weight in kg) (1370 +/- 68 (s.e.m.) kcal/day). Results by either estimate were not statistically different from the measured resting energy expenditure (MREE) (1382 +/- 130 (s.e.m.) kcal/day), by one-way analysis of variance. No multiplication factors were needed to relate the Harris-Benedict formula to MREE in this critically ill population and the estimate by the empirical formula was as good and simpler to perform. Although values by the Harris-Benedict formula and empirical formula correlated significantly with MREE (P less than 0.05) the correlation coefficients were low: 0.48 and 0.45 respectively. Thus, mean estimates were excellent for the group but less predictive for the individual. Multiple linear regressions did reveal that body composition and metabolic stress were of greater predictive value, since an equation relating weight (P less than 0.003), sex (P less than 0.003), white blood cell count (P less than 0.003) and 24-h urinary creatinine excretion (P less than 0.05) could predict 76 per cent of the variation (r = 0.87) in the MREE with an overall significance of P = 0.0002. Given the importance of matching energy intake to needs in many critically ill patients who are mechanically ventilated, accurate measurement of the REE is recommended now that instrumentation is equal to the task.

Adult↗