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R N Goldberg

Publications and source records attributed to R N Goldberg.

At least 19 recordsLinked to original sources

Standard thermodynamic formation properties for the adenosine 5'-triphosphate series.

The criterion for chemical equilibrium at specified temperature, pressure, pH, concentration of free magnesium ion, and ionic strength is the transformed Gibbs energy, which can be calculated from the Gibbs energy. The apparent equilibrium constant (written in terms of the total concentrations of reactants like adenosine 5'-triphosphate, rather than in terms of species) yields the standard transformed Gibbs energy of reaction, and the effect of temperature on the apparent equilibrium constant at specified pressure, pH, concentration of free magnesium ion, and ionic strength yields the standard transformed enthalpy of reaction. From the apparent equilibrium constants and standard transformed enthalpies of reaction that have been measured in the adenosine 5'-triphosphate series and the dissociation constants of the weak acids and magnesium complexes involved, it is possible to calculate standard Gibbs energies of formation and standard enthalpies of formation of the species involved at zero ionic strength. This requires the convention that the standard Gibbs energy of formation and standard enthalpy of formation for adenosine in dilute aqueous solutions be set equal to zero. On the basis of this convention, standard transformed Gibbs energies of formation and standard transformed enthalpies of formation of adenosine 5'-trisphosphate, adenosine 5'-diphosphate, adenosine 5'-monophosphate, and adenosine at 298.15 K, 1 bar, pH = 7, a concentration of free magnesium ions of 10(-3) M, and an ionic strength of 0.25 M have been calculated.

Adenine Nucleotides

A cohort study of transcutaneous oxygen tension and the incidence and severity of retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity is a disease affecting the blood vessels of the retina in premature infants that may result in scarring, retinal detachment, and loss of vision. An association between this condition and the exposure of premature infants to supplemental oxygen has been postulated, but the relation between retinopathy of prematurity and blood oxygen levels has not been defined. The purpose of this study of a cohort of preterm infants was to correlate the incidence and severity of retinopathy of prematurity with the duration of exposure to different ranges of oxygen tension as measured by transcutaneous monitoring (tcPO2). METHODS: One hundred one premature infants (birth weight, 500 to 1300 g) requiring supplemental oxygen had continuous monitoring of tcPO2. The number of hours during which the tcPO2 was 80 mm Hg or higher was tabulated for each infant during the first four weeks of life. RESULTS: There was a significant association between the amount of time that the tcPO2 was greater than or equal to 80 mm Hg and the incidence and severity of retinopathy of prematurity. The odds ratio for each 12-hour period in which the tcPO2 was greater than or equal to 80 mm Hg was 1.9 (95 percent confidence interval, 1.2 to 3.0) after adjustment for the following factors: birth weight less than or equal to 1300 g (odds ratio, 2.3 [95 percent confidence interval, 1.6 to 3.4]), five-minute Apgar score of 7 or less (odds ratio, 7.2 [95 percent confidence interval, 2.5 to 21]), and exposure to inspired oxygen at a concentration greater than or equal to 0.4 (odds ratio, 1.0 [95 percent confidence interval, 0.97 to 1.05]). The association was stronger for tcPO2 values of greater than or equal to 80 mm Hg occurring from the second through the fourth week of life; during this period, the adjusted odds ratio for a 12-hour period of such exposure was 3.1 (95 percent confidence interval, 1.6 to 6.1). CONCLUSIONS: This study supports an association between the incidence and severity of retinopathy of prematurity and the duration of exposure to arterial oxygen levels of 80 mm Hg or higher, measured transcutaneously.

Apgar Score

Hemodynamic effects of continuous negative extrathoracic pressure and continuous positive airway pressure in piglets with normal lungs.

The hemodynamic effects produced by continuous positive airway pressure (CPAP) and continuous negative extrathoracic pressure (CNEP) of 4 and 8 cm H2O were compared in 8 normal, spontaneously breathing piglets. Arterial blood gases and hemodynamic measurements were obtained before and during CPAP and CNEP of 4 and 8 cm H2O. CPAP 8 cm H2O and CNEP 8 cm H2O produced significant increases (p less than 0.01) in PaO2 from baselines 76 +/- 3 to 85 +/- 3 and 77 +/- 4 to 85 +/- 3 mm Hg, respectively. No significant changes occurred in PaCO2 or cardiac index, except during CPAP 8 cm H2O [38 +/- 1 to 44 +/- 2 mm Hg (p less than 0.05) and 376 +/- 30 to 330 +/- 30 ml/kg/min (p less than 0.05), respectively]. During CPAP of 4 cm H2O, significant increases occurred in mean right atrial pressure (Pra) (2.1 +/- 0.3 to 3.3 +/- 0.4 mm Hg; p less than 0.01), left ventricular end-diastolic pressure (LVEDP) (2.8 +/- 0.4 to 3.7 +/- 0.3 mm Hg; p less than 0.01), and mean pulmonary artery pressure (Ppa) (12.9 +/- 0.8 to 15.1 +/- 0.8 mm Hg; p less than 0.01). CPAP of 8 cm H2O produced marked increases in Pra (2.1 +/- 0.2 to 4.9 +/- 0.7 mm Hg; p less than 0.01), LVEDP (2.7 +/- 0.5 to 4.5 +/- 0.4 mm Hg; p less than 0.01) and Ppa (12.8 +/- 0.8 to 17.7 +/- 0.6 mm Hg; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effectiveness of a gentamicin dosing protocol based on postconceptional age: comparison to published neonatal guidelines.

OBJECTIVE: To evaluate the effectiveness of a gentamicin dosing protocol based on postconceptional age in producing therapeutic serum concentrations and to compare the protocol with commonly used gentamicin dosing guidelines. DESIGN: During the initial three months of this study infants were dosed according to physician discretion (group I). In the subsequent three-month period patients were dosed according to a postconceptional age dosing schedule (group II). SETTING: Infants were enrolled after being admitted to the Newborn Intensive Care Unit at the University of Miami/Jackson Memorial Medical Center. PATIENTS: Infants less than 37 weeks gestational age with normal renal function, not receiving indomethacin, and requiring gentamicin treatment were enrolled. Fifty-nine infants were enrolled into group I (median weight 1300 g [range 720-3300]), postconceptional age 29 weeks [26-37]); and 68 infants were enrolled into group II (weight 970 g [530-3000], postconceptional age 29 weeks [24-36]). INTERVENTION: Patients in group II were dosed according to the following protocol: postconceptional age less than 30 weeks, 3.0 mg/kg q24h, and postconceptional age 30-37 weeks, 2.5 mg/kg q18h. Peak and trough serum gentamicin concentrations were obtained in all study patients. Pharmacokinetic parameters were calculated from measured serum concentrations. Using the calculated pharmacokinetic data, peak and trough serum concentrations were simulated for five published neonatal dosing guidelines and the proposed postconceptional age protocol. MAIN OUTCOME MEASURES: The number of therapeutic serum gentamicin concentrations resulting from the dosing guidelines studied were compared. RESULTS: Measured trough concentrations differed significantly between the two groups with 35 percent of patients in group I and 90 percent of patients in group II having trough values less than 2 mg/L (p less than 0.001). There was no significant difference in measured peak concentrations between groups. Simulated trough concentrations were significantly different when postconceptional age dosing was compared with commonly used protocols (p less than 0.0001) with the highest percentage of concentrations less than 2 mg/L (89 percent) resulting from the proposed postconceptional age guidelines. CONCLUSIONS: These data suggest that the proposed postconceptional age protocol is reproducible and reliable in achieving therapeutic gentamicin serum concentrations in neonates.

Drug Administration Schedule

Effect of cyclooxygenase inhibition on retinal and choroidal blood flow during hypercarbia in newborn piglets.

The effect of the cyclooxygenase inhibitor, indomethacin, on choroidal (ChBF) and retinal (RBF) blood flow during hypercarbia was examined in 16 paralyzed and mechanically ventilated piglets less than 8 d old. The animals were randomly assigned to a control group (mean +/- SEM: wt, 1.66 +/- 0.1 kg; n = 8) that received a placebo infusion or to an indomethacin treatment group (wt, 1.68 +/- 0.2 kg; n = 8) that received an infusion of indomethacin (5 mg/kg i.v. over 30 min). Baseline ChBF and RBF were measured using radiolabeled microspheres in room air before and 15 min after the administration of placebo or indomethacin. Animals were then exposed to 30 min of hypercarbia (6-7% CO2, arterial CO2 pressure 8-10 kPa) and measurements were repeated. There were no significant differences in RBF between control (40 +/- 3 mL/min/100 g) and indomethacin-treated animals (40 +/- 3 mL/min/100 g) before administration of placebo or indomethacin. However, RBF decreased significantly in the indomethacin-treated animals (28 +/- 2 mL/min/100 g) compared to the control group (42 +/- 4 mL/min/100 g) 15 min after administration of placebo or indomethacin. Furthermore, an increase in RBF occurred during hypercarbia in the control group (86 +/- 6 mL/min/100 g), but this change was blunted in the indomethacin-treated animals (33 +/- 5 mL/min/100 g) (p less than 0.001). In contrast, ChBF did not differ significantly between the control and indomethacin groups during the periods studied. These results suggest that the increase in RBF during hypercarbia is at least partially mediated by cyclooxygenase by-products of arachidonic acid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of pentoxifylline on the cardiovascular manifestations of group B streptococcal sepsis in the piglet.

Pentoxifylline (PTXF) is a methylxanthine that modifies leukocyte function and inhibits cytokine release. To evaluate its effects on the cardiovascular manifestations of sepsis secondary to group B streptococci, 14 anesthetized, mechanically ventilated piglets were studied over a 240-min period. Animals were randomly assigned to a treatment group that received a PTXF bolus (20 mg/kg) followed by a continuous infusion of 5 mg/kg/h before and during group B streptococci (1 x 10(8) colony forming units/kg/min) administration and a control group that received saline as a placebo. Comparison of the hemodynamic measurements and arterial blood gases during the first 90 min of PTXF treatment with those of the control group resulted in the following 90 min values: systemic arterial blood pressure was significantly higher in the PTXF group (89 +/- 10 versus 56 +/- 30 mm Hg; p less than 0.005) as was cardiac output (0.18 +/- 0.04 versus 0.10 +/- 0.07 L/kg/min; p less than 0.005). Pulmonary vascular resistance remained lower in the PTXF-treated animals (135 +/- 117 versus 248 +/- 119 mm Hg/L/min/kg; p less than 0.001), and these animals were less acidotic as measured by pH (7.07 +/- 0.2 versus 7.31 +/- 0.1; p less than 0.05) and base deficit (-15 +/- 9 versus -5 +/- 2 mmol/L; p less than 0.05). Median survival time was significantly longer in the PTXF group (210 versus 90 min; p less than 0.002). These data demonstrate that PTXF can ameliorate some of the deleterious hemodynamic manifestations of group B streptococci sepsis and result in improved survival in a young animal model.

Acid-Base Equilibrium

Thermodynamics of hydrolysis of disaccharides. Lactulose, alpha-D-melibiose, palatinose, D-trehalose, D-turanose and 3-o-beta-D-galactopyranosyl-D-arabinose.

High-pressure liquid chromatography and microcalorimetry have been used to study the thermodynamics of the hydrolysis reactions of a series of disaccharides. The enzymes used to bring about the hydrolyses were: beta-galactosidase for lactulose and 3-o-beta-D-galactopyranosyl-D-arabinose; beta-glucosidase for alpha-D-melibiose; beta-amylase for D-trehalose; isomaltase for palatinose; and alpha-glucosidase for D-turanose. The buffer used was sodium acetate (0.02-0.10 M and pH 4.44-5.65). For the following processes at 298.15 K: lactulose(aq) + H2O(liq) = D-galactose(aq) + D-fructose(aq), K0 = 128 +/- 10 and delta H0 = 2.21 +/- 0.10 kJ mol-1; alpha-D-melibiose(aq) + H2O(liq) = D-galactose(aq) + D-glucose(aq), K0 = 123 +/- 42 and delta H0 = -0.88 +/- 0.50 kJ mol-1; palatinose(aq) + H2O(liq) = D-glucose(aq) + D-fructose(aq), delta H0 = -4.44 +/- 1.1 kJ mol-1; D-trehalose(aq) + H2O(liq) = 2 D-glucose(aq), K0 = 119 +/- 10 and delta H0 = 4.73 +/- 0.41 kJ mol-1; D-turanose(aq) + H2O(liq) = D-glucose(aq) + D-fructose(aq), delta H0 = -2.68 +/- 0.75 kJ mol-1; and 3-o-beta-D-galactopyranosyl-D-arabinose(aq) + H2O(liq) = D-galactose(aq) + D- arabinose(aq),0H0 = 107 +/- 10 and delta H0 = 2.97 +/- 0.10 kJ mol-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry

Thermodynamics of hydrolysis of oligosaccharides.

Microcalorimetry has been used to determine enthalpy changes for the hydrolysis of a series of oligosaccharides. High-pressure liquid chromatography was used to determine the extents of reaction and to check for any possible side reactions. The enzyme glucan 1,4-alpha-glucosidase was used to bring about the following hydrolysis reactions: (A) maltose(aq) + H2O(liq) = 2D-glucose(aq); (B) maltotriose(aq) + 2H2O(liq) = 3D-glucose(aq); (C) maltotetraose(aq) + 3H2O(liq) = 4D-glucose(aq); (D) maltopentaose(aq) + 4H2O(liq) = 5D-glucose(aq); (E) maltohexaose(aq) + 5H2O(liq) = 6D-glucose(aq); (F) maltoheptaose(aq) + 6H2O(liq) = 7D-glucose(aq); (G) amylose(aq) + nH2O(liq) = (n + 1) D-glucose(aq); and (H) panose(aq) + 2H2O(liq) = 3D-glucose(aq); (J) isomaltotriose(aq) + 2H2O(liq) = 3D-glucose(aq). The enzyme beta-fructofuranosidase was used for the reactions: (K) raffinose(aq) + H2O(liq) = alpha-D-melibiose(aq) + D-fructose(aq); and (L) stachyose(aq) + H2O(liq) = o-alpha-D-galactopyranosyl-(1----6)- alpha-o-D-galactopyranosyl-(1----6)-alpha-D-glucopyranose + D-fructose(aq). The results of the calorimetric measurements (298.15 K, 0.1 M sodium acetate buffer, pH 4.44-6.00) are: delta H0A = -4.55 +/- 0.10, delta H0B = -9.03 +/- 0.10, delta H0C = -13.79 +/- 0.15, delta H0D = -18.12 +/- 0.10, delta H0E = -22.40 +/- 0.15, delta H0F = -26.81 +/- 0.20, delta H0H = 1.46 +/- 0.40, delta H0J = 11.4 +/- 2.0, delta H0K = -15.25 +/- 0.20, and delta H0L = -14.93 +/- 0.20 kJ mol-1. The enthalpies of hydrolysis of two different samples of amylose were 1062 +/- 20 and 2719 +/- 100 kJ mol-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylose

Hemodynamic effects of conventional and high frequency oscillatory ventilation in normal and septic piglets.

The cardiovascular effects of high frequency oscillation (HFO) and conventional ventilation (CMV) were evaluated in 10 piglets prior to and during an infusion of group B streptococci (GBS). Animals were randomized to begin ventilation with either HFO or CMV. Arterial blood gases, cardiac output (CO), and pulmonary artery (Ppa), pulmonary wedge (Ppw) and arterial blood pressures were measured. These values were recorded at a mean airway pressure (MAP) of 2 cm H2O for both modes of ventilation after which a continuous infusion of GBS (4 X 10(7) CFU/kg/min) was begun. MAP was increased in both ventilators in the following sequence: 4, 8 and 12 cm H2O. Prior to GBS infusion, HFO was associated with small but significant changes in hemodynamic parameters when compared to CMV for the following: Ppa (15 +/- 4 vs. 13 +/- 4.0 mm Hg; p less than 0.03), Ppw (3 +/- 1 vs. 2 +/- 1 mm Hg; p less than 0.02), and CO (0.24 +/- 0.08 vs. 0.25 +/- 0.09 l/min/kg; p less than 0.05). Similar statistically significant increases in Ppa (p less than 0.005) and Ppw (p less than 0.0001), and decrease in CO (p less than 0.007) were present during GBS infusion when animals were ventilated with HFO, irrespective of the MAP used. Our results suggest that the use of HFO in both normal piglets and those receiving an infusion of GBS results in mild but consistent impairment in cardiovascular function compared to CMV. In summary, these data demonstrate that HFO has no beneficial effect compared to CMV at similar MAP in the management of the septic piglet model and may in fact further compromise the animal's hemodynamic status.

Animals

A calorimetric and equilibrium investigation of the hydrolysis of lactose.

The thermodynamics of the hydrolysis of lactose to glucose and galactose have been investigated using both high pressure liquid chromatography and heat-conduction microcalorimetry. The reaction was carried out over the temperature range 282-316 K and in 0.1 M sodium acetate buffer at a pH of 5.65 using the enzyme beta-galactosidase to catalyze the reaction. For the process lactose(aq) + H2O(liq) = glucose(aq) + galactose(aq), delta G0 = -8.72 +/- 0.20 kJ.mol-1, K0 = 34 +/- 3, delta H0 = 0.44 +/- 0.11 kJ.mol-1, delta S0 = 30.7 +/- 0.8 J.mol-1.K-1, and delta Cop = 9 +/- 20 J.mol-1.K-1 at 298.15 K. The standard state is the hypothetical ideal solution of unit molality. Thermochemical cycle calculations using enthalpies of combustion and solution, entropies, solubilities, activity coefficients, and apparent molar heat capacities have also been performed. These calculations indicate large discrepancies which are attributable primarily to errors in literature data on the enthalpies of combustion and/or third law entropies of the crystalline forms of the substrates.

Calorimetry

Thermodynamics of hydrolysis of disaccharides. Cellobiose, gentiobiose, isomaltose, and maltose.

The thermodynamics of the enzymatic hydrolysis of cellobiose, gentiobiose, isomaltose, and maltose have been studied using both high pressure liquid chromatography and microcalorimetry. The hydrolysis reactions were carried out in aqueous sodium acetate buffer at a pH of 5.65 and over the temperature range of 286 to 316 K using the enzymes beta-glucosidase, isomaltase, and maltase. The thermodynamic parameters obtained for the hydrolysis reactions, disaccharide(aq) + H2O(liq) = 2 glucose(aq), at 298.15 K are: K greater than or equal to 155, delta G0 less than or equal to -12.5 kJ mol-1, and delta H0 = -2.43 +/- 0.31 kJ mol-1 for cellobiose; K = 17.9 +/- 0.7, delta G0 = -7.15 +/- 0.10 kJ mol-1 and delta H0 = 2.26 +/- 0.48 kJ mol-1 for gentiobiose; K = 17.25 +/- 0.7, delta G0 = -7.06 +/- 0.10 kJ mol-1, and delta H0 = 5.86 +/- 0.54 kJ mol-1 for isomaltose; and K greater than or equal to 513, delta G0 less than or equal to -15.5 kJ mol-1, and delta H0 = -4.02 +/- 0.15 kJ mol-1 for maltose. The standard state is the hypothetical ideal solution of unit molality. Due to enzymatic inhibition by glucose, it was not possible to obtain reliable values for the equilibrium constants for the hydrolysis of either cellobiose or maltose. The entropy changes for the hydrolysis reactions are in the range 32 to 43 J mol-1 K-1; the heat capacity changes are approximately equal to zero J mol-1 K-1. Additional pathways for calculating thermodynamic parameters for these hydrolysis reactions are discussed.

Calorimetry

Hyperammonemia associated with perinatal asphyxia.

Twelve infants with severe perinatal asphyxia were found to have elevated blood ammonia levels (302 to 960 microgram/100 ml). In the seven survivors, hyperammonemia was associated with CNS irritability, hyperthermia, hypertension, and wide neonatal heart rate oscillations. Follow-up examinations revealed severe neurologic dysfunction in five of seven infants. CNS depression, hyperthermia, hypertension, and a nonreactive, fixed heart rate characterized the infants that died. These findings suggest a clinical entity secondary to perinatal asphyxia whose signs and symptoms may be related to hyperammonemia.

Ammonia

Thermodynamics of hexokinase catalyzed reactions. II. Measurement and calculation of enthalpies of reaction as a function of magnesium ion concentration.

Enthalpies of phosphorylation of glucose by adenosine 5'-triphosphate have been measured as a function of concentrations of magnesium chloride in TRIS/TRIS-HCl buffer in the pH range 8.64 to 8.98. These measurements are compared with the results of calculations of these enthalpies that use a coupled equilibrium formalism with equilibrium data and enthalpy values selected from the literature. The experimental results span the range of magnesium ion concentrations 1 X 10(-6) to 0.3 mol alpha-1 and show a total variation in the enthalpy of reaction of almost 10 kJ mol-1, with the most exothermic reaction occurring at a magnesium ion concentration of 6.0 X 10(-4) mol alpha-1. The calculated enthalpies of reaction, except for the magnesium ion concentration range 4 X 10(-6) to 5 X 10(-4) mol alpha-1, are, within estimated uncertainty intervals (0.8 to 10.2 kJ mol-1), in agreement with the measured values.

Adenosine Triphosphate

Microcalorimetric determination of glucose in reference samples of serum.

Ireport a detailed series of microcalorimetric measurement of glucose concentrations in five reference samples of serum. The method utilized (a) calibration in the actual medium of analysis and (b) a correction for interferences owing to the nonspecificity of the enzyme hexokinase. The microcalorimetric results are compared with the tentative results of analyses obtained by the spectrophotometric hexokinase/glucose-6-phosphate dehydrogenase method and by isotope-dilution mass spectrometry. In most cases, the microcalorimetric results appear to be in agreement with the results obtained by these latter two methods. A discussion of the basis of the microcalorimetric measurements is presented.

Adenosine Triphosphate