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The first detailed study of the J-based configuration analysis method in chlorinated hydrocarbons and chlorohydrins is presented along with the development of a spectroscopic database that facilitates configurational assignment of these structures. The data are generated through the investigation of model structures in solution by NMR spectroscopic methods and in the solid state by X-ray crystallography. Consequently, complete conformational analysis of trichlorinated hexane-1,2- and -1,3-diols is presented. The investigations in chlorinated systems for the first time attest to the relevance, reliability, and accuracy of the spectroscopic approach in configurational assignment, which had been otherwise developed for polyketides. During the synthesis of the various molecules that constitute the database and exemplify the various possible stereochemical patterns, a number of observations were made that underscore the unique features of these chlorinated systems. Thus, certain diastereomeric subclasses of 4,5-dichloro-2,3-epoxyhexane-1-ols display a propensity to undergo ring-opening reactions at C-3 with concomitant inversion of configuration at the neighboring C-Cl at C4, implicating the intermediacy of chloronium ions. The observations of positional and stereochemical scrambling in polychlorinated hydrocarbons underscore the necessity of a spectroscopic database that enables rapid, reliable configurational assignment of chlorinated natural products and intermediates en route to these.

OBJECTIVE To use stable isotopes for the analysis of hepatic metabolic pathways (urea synthesis, glucose production), comparing them in alcoholic and normal liver, in order to obtain specific and quantitative information on metabolic functions of the liver. PATIENTS AND METHODS Urea and glucose production as well as alanine metabolism in the liver were studied by means of stable isotopes in 7 males with alcoholic liver cirrhosis (mean age 46 +/- 4 years; height 173 +/- 5 cm; weight 73 +/- 3 kg) and 7 healthy male volunteers as controls (age 26 +/- 3 years; height 180 +/- 5 cm; weight 75 +/- 6 kg). The plasma concentrations of adrenaline, noradrenaline, insulin, glucagon and amino-acids were also measured. RESULTS Urea synthesis was lower in the cirrhosis patients than in the controls (3.3 +/- 2.2 mumol/kg.min vs 4.8 +/- 0.9 mumol/kg.min, P < 0.05). But there were no differences in glucose production, alanine metabolism and adrenaline concentrations. The concentrations of glutamine, phenylalanine, tyrosine, insulin, glucagon and noradrenaline were significantly raised in the cirrhotic patients, those of valine and leucine significantly lower. CONCLUSIONS Contrary to hepatic glucose production, which was within normal limits, urea synthesis was reduced by 30% in the cirrhotic patients. The use of stable isotopes provided detailed information on specific metabolic processes in cirrhotic livers.

Objective The aim of the study was to characterize the metabolic changes in non–weight-losing patients with cancer of the bladder and to investigate the effect of tumor stage. Methods The kinetics of glucose, glycerol, and urea metabolism were assessed in 22 weight-stable patients with non-metastatic bladder cancer (tumor stage p ≤ T2, n = 8; tumor stage p > T2, n = 14) and 10 patients with benign uterine myoma (controls). The kinetics of glucose, glycerol, and urea metabolism were assessed by [6,6- 2 H 2 ]glucose, [1,1,2,3,3- 2 H 5 ]glycerol, and [ 15 N 2 ]urea. Plasma concentrations of glucose, glycerol, urea, lactate, free fatty acids, insulin, glucagon, cortisol, epinephrine, and norepinephrine also were determined. Results Plasma concentrations of glucose, urea, and insulin were higher in cancer patients than in controls ( P P P T2). Conclusion Patients with bladder cancer had a lower rate of glucose clearance than did control subjects. Lipid metabolism was not affected, whereas urea synthesis rate was elevated in cancer patients. However, when expressed per kilogram of fat-free body mass, no difference in protein breakdown could be observed. The tumor stage had no effect on glucose, lipid, or protein metabolism.

(1998). The hyperglycaemic response to surgery: pathophysiology, clinical implications and modification by the anaesthetic technique. Clinical Intensive Care: Vol. 9, No. 3, pp. 118-128.

Ziel dieser Arbeit ist es, die nicht-energetische Bedeutung der klassischen Energietrager Kohlenhydrate und Fette im Rahmen parenteraler Ernahrungskonzepte darzustellen. Basierend auf der pharmakologischen Funktion dieser Nahrsubstrate im Kontext der pathophysiologischen Veranderungen des Organ- und Intermediarstoffwechsels definiert sich eine Ernahrungsstrategie, die versucht, eine differenzierte, auf einzelne Krankheitsbilder abgestimmte Nahrstoffzufuhr durchzufuhren.

We report the case of a 41-year-old male with hyper-dynamic septic shock requiring noradrenaline in addition to volume resuscitation in order to maintain a mean arterial blood pressure >70 mmHg. However, despite satisfactory global haemodynamics and gas exchange, he exhibited persistent renal failure and hepatic dysfunction (MGEX 1,000 U/l) as well as gastric intramucosal acidosis (pHi 7.17). In an attempt to improve splanchnic O2 delivery we tested the effects of infusions of dobutamine (10 μg/kg/ min) and dopexamine (2 μg/kg/min). In addition to measuring splanchnic blood flow using the steady-state infusion indocyanine-green clearance technique, we analysed the hepatic metabolic response. The latter was estimated by determination of the hepatic glucose production rate (HGP), and splanchnic alanine uptake and lactate clearance. Both drugs comparably increased splanchnic blood flow and O2 availability. While both splanchnic O2 and alanin...

To determine the magnitude and time course of adrenergic effects on metabolism in volunteers and possible implications for the use of sympathomimetics in the critically ill.Descriptive laboratory investigation.7 volunteers.Primed continuous infusions of stable isotope tracers ([15N2]-urea, [6,6-D2]-glucose, [methyl-D3]-L-leucine, [15N]-L-alanine) were used. After isotopic steady state had been reached an infusion of adrenaline (0.1 microgram/kg/min) was administered (4 h). Isotopic enrichment was measured using gas chromatography-mass spectrometry and the corresponding rates of appearance were calculated.Glucose production increased from 14.1 +/- 1.2 to 21.5 +/- 2.0 mumol/kg/min (p0.05) after 80 min of adrenergic stimulation and then decreased again to 17.9 +/- 1.2 mumol/kg/min after 240 min. Leucine and ketoisocaproate (KIC) fluxes were 2.3 +/- 0.2 and 2.6 +/- 0.2 mumol/kg/min, respectively, at baseline and gradually decreased to 1.8 +/- 0.2 and 2.2 +/- 0.1 mumol/kg/min, respectively, after 240 min of adrenaline infusion (both p0.05). Alanine flux increased from 3.7 +/- 0.5 to 6.9 +/- 0.9 mumol/kg/min (p0.05) after 80 min of adrenergic stimulation. Urea production slightly decreased from 4.8 +/- 0.9 to 4.3 +/- 0.8 mumol/kg/min during adrenaline (p0.05).Adrenaline induced an increase in glucose production lasting for longer than 240 min. The decrease in leucine and KIC flux suggests a reduction in proteolysis, which was supported by the decrease in urea production. The increase in alanine flux is therefore most likely due to an increase in de-novo synthesis. The ammonia donor for alanine synthesis in peripheral tissues and the target for ammonia after alanine deamination in the liver remain to be investigated. These results indicate that adrenaline infusion most probably will not promote already enhanced proteolysis in critically ill patients. Gluconeogenesis is an energy consuming process and an increase may deteriorate hepatic oxygen balance in patients.

We performed a 5-year, retrospective study using records of 1081 patients admitted to the trauma emergency room at a University Hospital to investigate the occurrence of tracheal tube malpositioning after emergency intubation in both the inpatient and outpatient settings, using chest radiographs and CT scans in the trauma emergency room. Prehospital patients and inpatients referred from peripheral hospitals were compared. This study showed that tracheal tube misplacements occur with an incidence of 18.2%, of which almost a third (5.7%) were placed in a main bronchus. We further show that tracheal intubation in emergency patients approximates the misplacement rates in the prehospital or in-hospital settings. We speculate that the skill level of the operator may be critical in determining the success of tracheal intubation. Based on our findings, all efforts should be made to verify the tube position with immediate radiographic confirmation after admission to the emergency room.

BACKGROUND The aim of this study was to determine the impact of sevoflurane anaesthesia on metabolic and endocrine responses to lower abdominal surgery. METHODS A prospective randomized controlled study in 20 patients undergoing abdominal hysterectomy. Patients were randomly assigned to receive either sevoflurane (S) or isoflurane anaesthesia (I). Using a stable isotope dilution technique, endogenous glucose production (EGP) and plasma glucose clearance (GC) were determined pre- and postoperatively (6,6-2H2-glucose). Plasma concentrations of glucose, insulin, cortisol, epinephrine and norepinephrine were measured preoperatively, 5 min after induction of anaesthesia, during surgery and 2 h after the operation. RESULTS EGP increased in both groups with no intergroup differences (preop. S 12.2 +/- 1.6, I 12.4 +/- 1.6; postop. S 16.3 +/- 1.9*, I 19.0 +/- 3.1* micromol kg(-1) min(-1), all values are means +/- SD, *P < 0.05 vs. preop.). Plasma glucose concentration increased and GC decreased in both groups. There were no differences between groups. (Glucose conc. mmol l(-1) preop.: S 4.1 +/- 0.3, I 3.9 +/- 0.5; 5 AI S 5.1 +/- 0.6*, I 5.1 +/- 1.0*, postop. S 7.0 +/- 1.0*, I 7.1 +/- 1.4*; * = P < 0.05 vs. preop.; GC ml kg(-1)min(-1) preop. S 3.0 +/- 0.4, I 3.2 +/- 0.4; postop. S 2.4 +/- 0.3*, I 2.7 +/- 0.3*; *=P < 0.05 vs. preop.) Insulin plasma concentrations were unchanged. Cortisol plasma concentrations increased intra- and postoperatively with no changes between the groups. Norepinephrine plasma concentration increased in the S group after induction of anaesthesia. I group norepinephrine was increased 2 h after operation and showed no intergroup differences. CONCLUSION Sevoflurane, as well as isoflurane, does not prevent the metabolic endocrine responses to surgery.

The objective of the present study was to evaluate the effects of norepinephrine (n = 9) and dobutamine (n = 7) on carbohydrate and protein metabolism in healthy volunteers in comparison with a control group (n = 9). Norepinephrine (0.1 microg/kg min), dobutamine (5 microg/kg min), or placebo was infused for 240 min. The plasma concentration of glucose, lactate, epinephrine, norepinephrine, insulin, and glucagon were determined. Glucose and urea production and leucine flux were measured using a tracer technique. Norepinephrine caused a persisting rise in plasma glucose concentration, whereas the increase in glucose production was only transient. A minor increase in plasma lactate concentration was observed, but it did not exceed the physiological range. No change in leucine flux, urea production, or plasma concentration of insulin, glucagon, or epinephrine was found. Dobutamine slightly decreased glucose production, whereas the plasma concentration of glucose and lactate did not change. The reduction in leucine flux was paralleled by a decrease in urea production. No change in the plasma concentration of insulin, glucagon, or the catecholamines was observed. In conclusion, both norepinephrine and dobutamine have only minor metabolic effects. Because glucose production is enhanced by alpha1- and beta2-adrenoceptor stimulation, we conclude that dobutamine is only a weak agonist at these adrenoceptors. These minor metabolic actions may make both compounds suitable for critically ill patients because no further increase in metabolic rate should be caused.

We investigated the influence of propofol/sufentanil anesthesia on metabolic and endocrine responses during, and immediately after, lower abdominal surgery. Twenty otherwise healthy patients undergoing abdominal hysterectomy for benign myoma received either continuous infusions of propofol supplemented with sufentanil (0.01 microg. kg(-1). min(-1), n = 10) or enflurane anesthesia (enflurane, n = 10). Plasma concentrations of glucose, lactate, free fatty acids, triglycerides, insulin, glucagon, cortisol, epinephrine, and norepinephrine were measured before, during, and 2 h after surgery. Pre- and postoperative endogenous glucose production (R(a) glucose) was analyzed by an isotope dilution technique by using [6,6-(2)H(2)] glucose. Propofol/sufentanil anesthesia prevented the increase in plasma cortisol and catecholamine concentrations and attenuated the hyperglycemic response during surgery without showing any difference after the operation. Mediated through a higher glucagon/insulin quotient (propofol/sufentanil 15 +/- 7 versus enflurane 8 +/- 4 pg/microU, P0.05), the R(a) glucose postoperatively increased more in the propofol/sufentanil than in the enflurane group (propofol/sufentanil 15.6 +/- 2.0 versus enflurane 13.4 +/- 2.2 micromol. kg(-1). min(-1), P0.05).The concept of stress-free anesthesia using propofol combined with sufentanil is valid only during surgery. The metabolic endocrine stress response 2 h after the operation is more pronounced than after inhaled anesthesia.

OBJECTIVE To evaluate metabolic and calorigenic effects of dopexamine in healthy volunteers. DESIGN Prospective, randomized trial. SETTING Laboratory of the University Department of Anesthesiology. SUBJECTS Eight volunteers. INTERVENTIONS After a control period, dopexamine was administered using four infusion rates (0.75, 1.5, 3.0, and 6.0 microg/kg/min). MEASUREMENTS AND MAIN RESULTS Blood pressure, heart rate, oxygen consumption (VO2), and the plasma concentration of potassium, glucose, lactate, and norepinephrine were measured. Typical hemodynamic responses were seen. VO2 increased from 122 +/- 11 (SD) to 150 +/- 9 mL/min/m2 during the highest dopexamine infusion rate. Plasma potassium concentration decreased only during the highest infusion rate. Plasma glucose concentration increased during infusion rates of 3 and 6 microg/kg/min of dopexamine, from 90 +/- 5 to 99 +/- 5 mg/dL (5.0 +/- 0.3 to 5.5 +/- 0.3 mmol/L), and from 87 +/- 7 to 103 +/- 11 mg/dL (4.8 +/- 0.4 to 5.7 +/- 0.6 mmol/L), respectively. Lactate did not increase during dopexamine infusion. Plasma norepinephrine concentration increased during all four infusion rates. CONCLUSION It was not possible to differentiate the adrenergic receptor subtype responsible for the calorigenic and metabolic effects, since the putative beta2 adrenergic-receptor agonist, dopexamine, caused an increase in the plasma concentration of the beta1 adrenergic-receptor agonist, norepinephrine. Since beta2 adrenergic receptor-mediated effects such as hypokalemia were found only at infusion rates > or = 3 microg/kg/min, the effects of dopexamine at infusion rates < 3 microg/kg/min may be mainly mediated by stimulation of dopaminergic receptors and the indirect sympathomimetic action.

The object of this review is to demonstrate the non-nutritional importance of carbohydrates and fat as they represent the classic energy carriers in parenteral nutrition. Concerning the pathophysiological changes of organ metabolism and intermediary metabolism as well as the pharmacological function of this nutritive substrates it is necessary to adjust parenteral nutrition strategy to various clinical pictures. The major goals of parenteral applicated carbohydrates are to avoid hyperglycemia, to return the increased hepatic glucose production during trauma and sepsis back to normal, and to reduce protein catabolism. Realizing this goals the dosage of glucose infusion underlies close metabolic borders depending on the present disease. Because of favourable effects of hepatic glucose and protein metabolism, xylitol, a non-glucose polyol, represents an useful alternative energy source to glucose. The non-energetic nutrition therapy with fat consists of application of the essential fatty acids linoleic and alpha-linolenic acid and considers the immunmodulatory effects of various fatty acids as precursors in the eicosanoid metabolism. As demonstrated at the organ systems of liver and lung this pharmacological effects of any lipid infusion might influence specific organ functions.

Background Septic shock leads to increased splanchnic blood flow (Qspl) and oxygen consumption (VO2spl). The increased Qspl, however may not match the splanchnic oxygen demand, resulting in hepatic dysfunction. This concept of ongoing tissue hypoxia that can be relieved by increasing splanchnic oxygen delivery (DO2spl), however, was challenged because most of the elevated VO2spl was attributed to increased hepatic glucose production (HGP) resulting from increased substrate delivery. Therefore the authors tested the hypothesis that a dobutamine-induced increase in Qspl and DO2spl leads to increased VO2spl associated with accelerated HGP in patients with septic shock. Methods Twelve patients with hyperdynamic septic shock in whom blood pressure had been stabilized (mean arterial pressure > or = 70 mmHg) with volume resuscitation and norepinephrine received dobutamine to obtain a 20% increase in cardiac index (CI). Qspl, DO2spl, and VO2spl were assessed using the steady-state indocyanine green clearance technique with correction for hepatic dye extraction, and HGP was determined from the plasma appearance rate of stable, non-radio-active-labeled glucose using a primed-constant infusion approach. Results Although the increase in CI resulted in a similar increase in Qspl (from 0.91 +/- 0.21 to 1.21 +/- 0.34l.min-1.m2; P < 0.001) producing a parallel increase of DO2spl (from 141 +/- 33 to 182 +/- 44 ml.min-1.m2; P < 0.001), there was no effect on VO2spl (73 +/- 16 and 82 +/- 21 ml.min-1.m2, respectively). Hepatic glucose production decreased from 5.1 +/- 1.6 to 3.6 +/- 0.9 mg.kg-1.min-1 (P < 0.001). Conclusions In the patients with septic shock in whom blood pressure had been stabilized with volume resuscitation and norepinephrine, no delivery-dependency of VO2spl could be detected. Oxygen consumption was not related to the accelerated HGP either, and thus the concept that HGP dominates VO2spl must be questioned in well-resuscitated patients with septic shock.

To use stable isotopes for the analysis of hepatic metabolic pathways (urea synthesis, glucose production), comparing them in alcoholic and normal liver, in order to obtain specific and quantitative information on metabolic functions of the liver.Urea and glucose production as well as alanine metabolism in the liver were studied by means of stable isotopes in 7 males with alcoholic liver cirrhosis (mean age 46 +/- 4 years; height 173 +/- 5 cm; weight 73 +/- 3 kg) and 7 healthy male volunteers as controls (age 26 +/- 3 years; height 180 +/- 5 cm; weight 75 +/- 6 kg). The plasma concentrations of adrenaline, noradrenaline, insulin, glucagon and amino-acids were also measured.Urea synthesis was lower in the cirrhosis patients than in the controls (3.3 +/- 2.2 mumol/kg.min vs 4.8 +/- 0.9 mumol/kg.min, P0.05). But there were no differences in glucose production, alanine metabolism and adrenaline concentrations. The concentrations of glutamine, phenylalanine, tyrosine, insulin, glucagon and noradrenaline were significantly raised in the cirrhotic patients, those of valine and leucine significantly lower.Contrary to hepatic glucose production, which was within normal limits, urea synthesis was reduced by 30% in the cirrhotic patients. The use of stable isotopes provided detailed information on specific metabolic processes in cirrhotic livers.

[chemical reaction: see text]. We report the reduction of 2,3-dihydroisoxazoles to beta-amino ketones and beta-amino alcohols. The latter are obtained in high diastereoselectivity with preference for the syn isomer.

Incorrect positioning of the endotracheal tube (ETT) within the airway after emergent intubation can result in serious complications. Accidental mainstem bronchus intubation is associated with contralateral atelectasis, tension pneumothorax, hypotension, and decreased survival. Conversely, failure to place the tube several centimeters beyond the vocal cords may result in inadvertent extubation, aspiration, pneumonia, or laryngeal spasm [1]. The aim of this study was to investigate the occurrence of ETT malpositioning after emergency intubation in the out-of-hospital setting.

The aim of this study was to investigate metabolic changes during and after abdominal hysterectomy with specific regard to glycerol metabolism. Seven otherwise healthy patients with benign uterine myoma were enrolled in this study. Glycerol turnover and hepatic glucose production were measured before and after the operation by using stable-isotope technique ([1,1,2,3,3-2H5]-glycerol, [6,6-2H2]-glucose). Metabolic substrates (glycerol, nonesterified fatty acids, β-hydroxybutyrate, glucose, lactate) and hormones (insulin, glucagon, cortisol, catecholamines) were determined pre-, intra-, and postoperatively. Hysterectomy was associated with an increase of postoperative glycerol turnover from 3.56 ± 1.28 to 6.46 ± 2.44 μmol · kg−1 · min−1 (P < 0.05). This increment was inversely related to the age of the patients (r = 0.872, P < 0.05). Glycerol concentration tended to increase perioperatively. These changes, however, were not of statistical significance. Hepatic glucose production and glucose plasma levels increased postoperatively from 9.75 ± 1.61 to 12.79 ± 1.45 μmol · kg−1·min−1 (P < 0.05) and 4.6 ± 0.9 to 6.2 ± 0.9 mmol/L (P < 0.05), respectively. Cortisol and catecholamine levels rose during and after surgery, while insulin and glucagon remained unchanged. The enhanced rate of lipolysis after hysterectomy was not detectable from plasma glycerol levels alone. The results of this study showed that using stable isotope technique allowed a more differentiated look at metabolic pathways than static plasma substrate concentrations, especially under perioperative conditions.