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Biomedical subjects

G Kleinberger

Publications and source records attributed to G Kleinberger.

At least 19 recordsLinked to original sources

Energy metabolism in patients with acute and chronic liver disease.

Energy expenditure and substrate oxidation rate for fat, glucose and protein were evaluated by indirect calorimetry in 20 normal individuals, 35 patients with acute hepatitis and 22 patients with biopsy-proven alcoholic cirrhosis in the postabsorptive state. Measurements were done in the resting state after an overnight fast (10 to 12 hr). Oxygen consumption (ml/min/1.73 m2) in normal subjects, in patients with acute hepatitis and in patients with cirrhosis was 206.5 +/- 4.0 (mean +/- S.E.M.), 216.4 +/- 4.7 and 228.8 +/- 7.1 (p less than 0.05 vs. controls), respectively. When related to body surface area (kcal/min/1.73 m2), resting energy expenditure did not differ between normal subjects (0.98 +/- 0.02), patients with acute hepatitis (1.03 +/- 0.02) and cirrhotic patients (1.06 +/- 0.03). However, when related to 24-hr urinary creatinine excretion as an estimate of lean body mass, energy expenditure was increased in cirrhosis (p less than 0.0001). In cirrhosis an inverse association between the severity of liver disease according to Pugh and oxygen consumption and resting energy expenditure was found. In cirrhotic patients the percentages of total calories derived from fat (86% +/- 5%), carbohydrate (2% +/- 4%) and protein (12% +/- 1%) were different from those of normal controls who metabolized 45% +/- 4%, 38% +/- 4%, 17% +/- 1%, respectively. In acute hepatitis no alterations in metabolism could be found apart from a decreased protein oxidation rate. In conclusion no appreciable changes in energy metabolism exist in acute hepatitis. The pattern of fuel use in cirrhosis resembles that in starvation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Beneficial effect of 8-ornithin vasopressin on renal dysfunction in decompensated cirrhosis.

In nine patients with decompensated alcoholic cirrhosis of the liver and impaired renal function the effect of 8-ornithin vasopressin (ornipressin) on renal function and haemodynamic parameters was studied. Ornipressin was infused at a dose of 6 IU/h over a period of four hours. During ornipressin infusion an improvement of renal function was achieved as indicated by an increase of creatinine clearance (76 (15)%; p less than 0.01), urine volume (108 (29)%; p less than 0.05) and sodium excretion (168 (30)%; p less than 0.05). The hyperdynamic circulation of hepatic failure, as characterised by increased cardiac index and heart rate as well as decreased systemic vascular resistance was reversed to a nearly normal circulatory state during ornipressin infusion. The raised noradrenaline plasma concentration (1.74 (0.31) ng/ml) and plasma renin activity (13.5 (3.9) ng/ml/h) were lowered during ornipressin infusion to 0.87 (0.21) ng/ml and 5.9 (2.1) ng/ml/h, respectively (p less than 0.01). The efficacy of a vasoconstrictor agent in reverting a hyperdynamic state and improving renal function provides evidence for the substantial role of accumulation of vasodilator substances and subsequent activation of sympathetic nervous system and renin-angiotensin-axis in the pathogenesis of renal dysfunction in hepatic failure. Values are expressed as mean (SE).

Female

Influence of fluid replacement on extravascular lung water (EVLW) in patients with diabetic ketoacidosis.

Fluid replacement is a major issue in the treatment of patients with diabetic ketoacidosis. During this therapy, development of pulmonary edema has been reported and attributed to an increase in pulmonary microvascular pressure and a decrease in colloid-osmotic pressure (COP). Because clinically apparent pulmonary edema is associated with an increase in extravascular lung water (EVLW) and impairment of pulmonary gas exchange, we studied the effect of fluid replacement on EVLW, COP, pulmonary hemodynamics and gas exchange parameters in 8 patients with diabetic ketoacidosis (blood glucose greater than 300 mg/dl, pH less than 7.1). EVLW was estimated by the thermal-dye technique. All variables were successively determined upon admission (A), after initial fluid replacement (IFR), when glucose had fallen below 180 mg/dl, after 8 h of intravenous glucose treatment (G), and after 24 h of total parenteral nutrition (TPN). Despite a total net fluid intake of 6.0 +/- 1.61, a significant decrease (p less than 0.001) in COP from 29.6 +/- 5.5 at A to 18.8 +/- 2.2 mmHg after TPE and a significant increase (p less than 0.001) in PCWP from 4 +/- 2 at A to 10 +/- 3 mmHg after TPE, EVLW remained almost unchanged. EVLW was 5.1 +/- 2.8 at A, 5.3 +/- 2.1 after IFR, 4.8 +/- 1.4 after G, and 5.3 +/- 1.7 ml/kg after TPN. However, PaO2 decreased from 137 +/- 17 at A to 87 +/- 10 mmHg after TPE (p less than 0.001), while Qs/Qt increased significantly (p less than 0.05). The alterations in gas exchange may be indicative of pulmonary dysfunction but as they were not associated with accumulation of EVLW, they may as well reflect the compensation of metabolic derangements in diabetic ketoacidosis.

Adult

[Energy metabolism in patients with severe heart failure].

Resting energy expenditure was measured by indirect calorimetry in 11 patients (8 men, 3 women) with severe heart failure. The study was done after an over night fast (10-12 h). 5 patients suffered from idiopathic cardiomyopathy, 5 patients from coronary heart disease and 1 patient from congestive heart failure following from viral myocarditis. The cardiac index was 2.09 +/- 0.5 l/min/m2, the pulmonary capillary wedge pressure 24.6 +/- 8.0 mm Hg. Resting energy expenditure was 1.175 +/- 0.176 kcal/min/1.73 m2. The basal energy expenditure calculated according to Harris and Benedict was 1.008 +/- 0.055 kcal/min/1.73 m2. The difference was statistically significant (p less than 0.05). Respiratory quotient was 0.775 +/- 0.06 as a result of a high oxidation rate for fat (64.8% of total energy expenditure). These results show that after an overnight fast the caloric requirements of patients with severe heart failure are increased. This increased energy expenditure could be an explanation for the malnutrition often found in patients with severe chronic heart failure.

Adult

Loading and maintenance dose for the determination of amino acid kinetics in plasma.

Intravenous bolus kinetics of amino acids and calculation of the kinetic parameters with an 1-compartment model revealed weak spots. Therefore, a new study design with a loading and maintenance dose and description of the plasma concentration time data with a 2-compartment model was created and studied in 9 healthy volunteers. After an over night fast the amino acid mixture Thomaeamin n 10% was infused with a loading dose of 20 mg AA/kg-1 X min-1 for 5 min and a maintenance dose of 5 mg AA/g-1 X min-1 for 55 min. The postinfusion period lasted 120 min. The PAA was determined with a Biotronic LC 6001 and the kinetic parameters were calculated by a Wang 2200 computer with the TOPFIT program package. The results showed mean values (means +/- SE) of the volume distribution between 4.7 +/- 0.6 till 9.4 +/- 1.8 liters, an elimination rate constant of 1.7 +/- 0.5 till 11.0 +/- 2.0 h-1, a total clearance of 186 +/- 37 till 846 +/- 66 ml X min-1 and transfer or endogenous production rate between 12 +/- 0.8 till 135 +/- 16 mumol kg-1 X h-1. The total transfer amounts to 17.6 mmol kg-1 X d-1 (= 2.2 g AA/kg-1 X d-1). It can be concluded that an optimal study design for the investigation of AA kinetics should increase the PAA levels 2-3 fold above basal during the infusion period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Parenteral nutrition in liver insufficiency].

In recent years various regimens for parenteral nutrition in liver insufficiency, containing glucose and fat for energy supply and a liver-adapted amino acid mixture for nitrogen supply, have been recommended. The substrates should be delivered in an all-in-one-solution which facilitates metabolic monitoring and decreases the risk of infections. For treatment of hepatic encephalopathy (HE), branched chain amino acids (BCAA) are recommended. The separation of parenteral nutrition from the treatment of HE makes it much easier to adapt the dosage of the BCAA to the clinical symptoms of the patients. In patients with a severe decrease of gluconeogenesis (spontaneous hypoglycemia below 3 mmol/l combined with a hyperlactemia above 7 mmol/l) or a decreased elimination rate of ammonia (production rate of urea nitrogen below 5 g/l combined with hyperammonemia above 100 mumol/l), an exogenous amino acid supply is not indicated.

Amino Acids, Branched-Chain

Elimination of amino acids in chronic renal failure.

Elimination of parenterally administered amino acids was investigated in patients with chronic renal failure (CRF) (10 on conservative treatment = CT, 13 on regular hemodialysis therapy = HD). In a bolus injection protocol 0.1 g amino acids as a 10% solution containing essential and nonessential amino acids were infused and pharmacokinetic parameters of 17 amino acids were calculated. The mean elimination half life was increased by 40% in CT and 87% in HD (p less than 0.001 CT and HD versus controls). Total clearance was reduced in CT (p less than 0.001 versus HD and controls). In CT clearance of phenylalanine, proline, alanine, histidine and arginine was reduced, of none of the amino acids elevated. In HD clearance of methionine, lysine, aspartic acid and serine was increased, of proline decreased. The total transfer rate was reduced in CT (p less than 0.025 versus controls) and transfer of threonine, aspartic acid, glutamic acid, alanine, histidine and arginine was reduced in these patients. Mainly due to elevated basal plasma concentration transfer of methionine was elevated in CT and HD. In dialysis patients transfer of isoleucine, tryptophan, glycine and serine was increased. Despite variations of absolute values of clearance between the two groups investigated relative clearance rates of amino acids were similar because of a uniform increase of clearance of about 37% in HD compared to CT (p less than 0.001). Results indicate that the elimination of parenterally administered amino acids is grossly altered in uremia and that in patients on CT and HD a uniform elimination pattern can be observed.

Amino Acids

[Bedside chest x-rays and extravascular lung water determination in intensive care patients].

Radiological staging of pulmonary oedema was compared with the determination of extra-vascular lung water by means of a double indicator dilution technique. One hundred and forty-six ward chest radiographs were evaluated and compared with the results of simultaneous measurements of lung water. Seventy-seven cases could be evaluated statistically. Chest x-rays regarded as normal corresponded to extra-vascular lung water of 5 to 9 ml./kg. body weight. Interstitial oedema (radiological stage I and II) corresponded to extravascular lung water levels of 8 to 12 ml./kg. Differentiation of stages I and II was not possible. During stage III, extra-vascular lung water was 15 to 21 ml./kg. A comparative analyses of these findings revealed a discrepancy of 34%. The reasons for this are discussed.

Adult

[Changes in and modulation of receptor activity in hepatic encephalopathy].

In hepatic encephalopathy (HE) brain uptake of large neutral amino acids is impaired with tryptophan crossing the blood brain barrier (BBB) to a much larger extent than all other competing amino acids (AA). The disturbance in the steady-state of transmitter is paralleled to the change of their kinetic data. This is reflected by an increase in serotonin (5-HT) synthesis and turnover, while the number of post-synaptic 5-HT1-binding sites is decreased, 5-HT2-receptor activity is dropping to a much smaller extent. On the other hand, presynaptic dopaminergic activity remains unchanged with no change in D2-receptor activity. Valine (VAL) improves the postsynaptic 5-HT function via modulating activity due to a regulatory mechanism at the membranal level in vitro and ex vivo. Furthermore, VAL leads to a significant reduction of serum ammonia (NH4+) and brain NH4+ concentration. VAL is able to antagonize the binding density diminishing effects of NH4+ on 5-HT binding sites. This effect could be characterized by the measurement of VAL binding sites being 5 to 10 fold higher than the number of leucin (LEU)-sites. Considering the chemical bonds involved in the attachment of biogenic amines and aminoacids (Schiff-bases equilibria) the modulating action of NH4+ on neural transmission may be clarified. Tryptamine can displace the postsynaptic binding of 5-HT in brain tissue and is a possible antagonist to physiological and pharmacological effects of 5-HT. The dynamic changes of the kinetic behaviour of tryptamine-binding might demonstrate a compensating effect as shown in an increase of tryptaminergic receptor activity. As a working hypothesis, the different relative strengths of electron-pair donor and -acceptor sites of both compounds are suggested to their complementary physiological interaction. GABA, an inhibitory transmitter of the CNS is diminished in its maximal binding capacity in severe HE and is independent of NH4+ influence. Furthermore, glutamate and aspartate-receptors decrease in experimentally induced hepatic coma. L-LEU shows modulating effects of glutamine binding. Glycin-activity is increased, while naloxone- and D-ala2-methionine-encephalinamid binding are not different from controls. These data demonstrate a different influence of various brain receptors and binding sites by HE and indicate a differentiated disturbance of (neuronal) membrane activity. Therefore disturbed interneuronal dynamics might be important pathophysiological mechanisms underlying hepatic coma.

Ammonia

[Liver function disorders and damage in critically ill intensive care patients].

The course of the disease of critically ill patients is complicated and prognosis worsened by failure of one or more organs. During intensive care monitoring and treatment of vital functions most attention usually is paid to the cardio-pulmonary and renal system; liver function is neglected rather often. In a retrospective study 100 critically ill patients were evaluated, who had serum bilirubin levels above 3,0 mg/dl, but no primary liver disease. Excluded were patients who had liver destruction caused for instance by liver abscess or metastases, and patients with acute hemolysis and extrahepatic cholestasis. Severe infection was the primary cause of disease in 64% of these critically ill patients without primary liver dysfunction; 52% patients had septicemia, 37% patients were in a post-operative or post-traumatic status, 28% patients had severe gastrointestinal complications, 23% had myocardial pump failure, 32% had protracted shock, 29% had hematological disease, 59% had lung failure, and 58% renal failure. It was tried to find a correlation between the different liver function parameters in this group of patients. In spite of rather pronounced pathological findings a statistically significant correlation could only be found between SGPT and SLDH. This study demonstrates the importance of liver involvement in critically ill patients on the one side and the necessity of comprehensive and repeatedly performed investigations of liver function in such patients on the other side.

Adolescent

[A double blind cross-over study with mepindolol-sulfate in patients with coronary heart disease (author's transl)].

UNLABELLED: The effect of mepindolol-sulfate (2 x 2.5 mg) was tested in 20 patients with coronary heart disease in a controlled study against placebo resp. propranolol (3 x 40 mg). RESULTS: 1. The frequency and intensity of anginal attacks were reduced significantly under mepindolol-sulfate therapy.-- 2. There was a significant improvement of ergometric exercise tolerance under mepindolol-sulfate therapy.--3. Additionally a reduction of ST-depression in ECG was found under mepindolol-sulfate.--4. In patients with coronary heart disease the clinical effect of mepindolol-sulfate in a daily dose of 2 x 2.5 mg was equal to propranolol in a daily dose of 3 x 40 mg.

Adrenergic beta-Antagonists

[Course and intensive treatment of acute falciparum malaria (author's transl)].

The case of a nineteen-year-old women with the cerebral form of malaria tropica is reported. She showed hyperpyrexia, abdominal manifestations, haemolysis and disseminated intravascular coagulation. Cerebral symptoms amounting to grade IV encephalopathy occurred. The patient responded rapidly to the administration of chloroquine, anticonvulsants, dextran, corticosteroids, antipyretics, blood and antithrombin III and her symptoms had almost completely vanished one week after the onset of therapy.

Acute Disease

[Haemodynamic effects of depot zinc protamine glucagon in heart failure (author's transl)].

In contrast to intravenously-administered crystallene glucagon, which acts for 20 minutes only, the depot form, zinc protamine glucagon, shows a prolonged haemodynamic action. Fourteen patients with pre-existing heart failure received a single dose of 20 mg Zn protamine glucagon intramuscularly. The stroke volume and cardiac output were increased, whereas the mean and end-diastolic pulmonary pressure were decreased, indicating a positive inotropic action of the administered drug. Heart rate and mean arterial pressure remained almost unchanged. The haemodynamic changes started 60 minutes after intramuscular administration of the drug, reached a maximum effect at 3 hours and started to decrease after the fourth hour. Zn protamine glucagon can, therefore, be considered a beneficial drug in the treatment of digitalis-resistant heart failure on the basis of its long duration of action and easy route of administration.

Aged