Anabolic steroids in polytrauma patients. Influence on renal nitrogen and amino acid losses: a double-blind study.

Severe trauma leads to considerable losses of nitrogen in the first days after the accident. As nutritional efforts cannot reduce these losses sufficiently, an adjunctive therapy using the anabolic steroid nandrolone decanoate (Nd) was applied. In a double-blind study 10 male multiple-traumatized patients each received 50 mg of Nd on day 3 and 25 mg of Nd on day 6 after the trauma, an additional 10 patients received placebo only. Both groups had identical nutritional support. Nitrogen balance, total nitrogen excretion as well as plasma amino acid concentration, and urine amino acid excretion were measured daily. The anabolic agent improved the nitrogen balance mainly by reducing nitrogen excretion. 3-Methylhistidine excretion and renal amino acid losses were decreased. Nandrolone decanoate increased the concentration of total plasma amino acids. The underlying principle seems to be an amino acid-saving mechanism with a renal site of action. It is shown that in the early posttraumatic period nandrolone decanoate improves nitrogen metabolism. Further studies are required to determine whether this offers a clinical benefit to trauma patients.

Combined enteral-parenteral nutrition versus total parenteral nutrition in brain-injured patients. A comparative study.

A comparative nutritional study in brain-injured patients (BIP) was performed to assess the influence of a combined enteral-parenteral nutrition (CN) and a total parenteral nutrition (TPN) on protein catabolism in the early posttraumatic period. 20 male BIP (Glasgow coma scale 5-7) were randomized to one of the two feeding regimes. Nutritional support was based on 150-175% basic energy expenditure. Amino acid intake was 1.4 g/kg/day in the TPN and 2.4 g/kg/day in the CN group. Negative nitrogen balance (NNB) averaged means = 11.3 g/m2/day (SEM = 3.06 g/m2/day) in the TPN group and means = 10.2 g/m2/day (SEM = 2.33 g/m2/day) in the CN group. Between both feeding regimes not statistically significant differences could be observed concerning mortality, N-balance, creatinine and 3-methylhistidine excretions. Protein concentration of the regurgitated gastric fluid was significantly higher in the CN than in the TPN study group. Data imply that both alimentary regimes are of similar value, but BIP with impaired gastric function, such as high tube reflux, are better treated by TPN.

[Enteral-parenteral feeding with high protein content in++ severe cranio-cerebral injuries]. / Enteral-parenterale Ernährung mit hohem Eiweissangebot bei schwerem Schädel Hirn-Trauma.

Brain injured patients (BIP) usually have hugh losses of nitrogen in the early posttraumatic period. Investigations on protein catabolism in 10 young male BIP, not being moribund, were performed to answer the question whether N-loss can be minimized by an enteral-parenteral nutrition with high protein content (greater than 2 g protein/kg body weight). N-balance, 24-h urinary excretion of creatinin and 3-methylhistidine were measured for 8 days after the accident. The alimentary regime, being adapted to body weight, included for an adult 70-kg patient the intake of 470 g carbohydrates, 170 g aminoacids/proteins and 45 g fats per day (3040 kcal/day = 12700 kJ/day with 112 kcal/g N = 468 kJ/g N). Laboratory data indicated a stimulated muscle turnover rate and a considerable protein catabolism. The waste of endogenous sources could therefore not be prevented by the presented combined nutritional regime.

Pharmacokinetic evaluation of a new maintenance solution for severely injured patients.

Nine severely injured patients (SIP) and 9 healthy controls received 20 min iv infusions of Aminoplasmal-LS-10 (2.15 ml/kg body wt containing 0.215 g amino acids). Employing the values of the plasma amino acid (AA) concentrations 3, 7, 15, 30, 45, 70, and 150 min after the end of the infusion, we calculated the elimination half-life (t 1/2), the elimination constant (k2), the total clearance (Cltot), and the transfer of the individual AA. The AA showed t 1/2 between 6 (Glu) and 23 (Thr) min. Comparing the metabolic kinetics of healthy controls and SIP, there were no statistical differences in t 1/2 or in k2. In the SIP, nearly all plasma AA showed increased transfer and Cltot, significantly for Thr (p < 0.05), Pro, Gly, Ala, Arg (p < 0.02), Glu (p < 0.01), and Met (p < 0.005). In contrast, the Cltot for Phe and Tyr were decreased. Except for Phe, Tyr, Met (enhanced values) and Arg (no change), the fasting values of AA concentrations in the SIP were diminished compared to those in the healthy controls. Based on the measured transfer, we have developed a new maintenance solution adapted to SIP. Compared with Aminoplasmal, it is necessary to apply AA concentrations which are increased in Lys, His, Phe, Tyr, Val, Ala, and Ser, and reduced in Arg, Pro, Leu, Ile, and Gly.

[Changes in the secretion of growth hormone in severely injured persons (author's transl)]. / Das Verhalten der hGH-Sekretion bei Schwerverletzten.

The secretion of growth hormone was studied in 25 severely injured persons during the adaptive and convalescent stage. The ages of the patients varied between 9--65 years. During the first few days after the trauma hormone concentrations rose to up to 7--15 times their normal upper limits (about 10 mU/l). In some cases the hormone levels subsequently fell to the lower limits of normal. No attempt was made to calculate average values and the reasons for the omission are stated. The results are discussed with reference to the metabolic condition of the severely injured persons.

[Studies on the kinetics of the RNA metabolism in the prostate of normal and castrated rats (author's transl)]. / Untersuchungen zur Kinetik des RNA-Stoffwechsels in der Prostata normaler und kastrierter Ratten.

In the prostate of adult Wistar rats the RNA/DNA quotient of the whole organ as well as the amount of RNA and DNA in the nucleus was measured at different times after castration. Furthermore the half-life time for the turnover of the RNA in the nucleus and the cytoplasm was determined for normal and castrated rats with the aid of pulse labelling using [5(-3)H]uridine. A mathematical model was developed to analyze the experimental results. This model enabled us to make differentiated statements on the heterogeneous nuclear RNA (hmRNA) and the remaining RNA in the nucleus. The evaluation of the experimental values gave the following results: 1. By deprivation of androgens the uptake of [3H]uridine into the prostate is lowered. 2. The amount of DNA in the morphologically intact nucleus remains constant at least up to the 12th day after castration. 3. 6 days after castration the amount of hmRNA decreases to 1/10 and that of cytoplasmic RNA to 1/4. 4. The half-life time for the decrease of the whole nuclear RNA is 3.7 d and that of the cytoplasmic RNA 1.7 d. 5. The half-life time for the turnover of hmRNA is 16 min and that of cytoplasmic RNA about 2 days. 6 days after castration the half-life times are unchanged. The experimental results suggest that the observed decrease of nuclear RNA following castration can mainly be attributed to a reduced synthesis of hnRNA, while the decrease of cytoplasmic RNA is first of all caused by an increase in RNA degradation.

[Glycine hydrazide as a bifunctional reagent for the synthesis of antigens with steroids as the immunodeterminant groups (author's transl)]. / Glycinhydrazid als bifunktionelles Reagenz zur Synthese von Antigenen mit Steroiden als immundeterminante Gruppen

The suitability of glycine hydrazide as a link between steroids and carrier proteins in the synthesis of antigens was examined. Testosterone was used as hapten; bovine serum albumin as carrier protein. The reaction described here of testosterone with glycine hydrazide to form testosterone glycylhydrazone acetate took place under milk conditions and the yield was nearly quantitative. Rabbits immunized with the new antigen developed specific antibodies against testosterone.

[In vivo studies on the metabolism of pyrimidine nucleosides (author's transl)]. / In-vivo-Untersuchungen zur Metabolisierung der Pyrimidinnucleoside

3H-labelled metabolites were determined in the perchloric acid-soluble fraction of blood plasma and liver of adult male Wistar rats, following the application of [5 - 3H]uridine. Ten minutes after the injection of uridine, only 20% of the total 3H activity of the plasma could be attributed to [3H]uridine. The remaining radioactivity was found chiefly in [3H]uracil (40%) and 3H2O (20%). In the liver, at 10 min, [3H]-uridine and [3H]uracil together accounted for less than 0.5% of the total radioactivity; about 70% of the radioactivity was due to [3H]beta-alanine, and 15% to 3H2O. 45 min after the injection, 70% of the radioactivity in the plasma was due to 3H2O, whereas uridine and uracil represented about 4% and 6%, respectively. At this time, about 55% of the radioactivity in the liver was due to [3H]beta-alanine, about 40% to 3H2O, and about 5% to unidentified metabolites; [3H]uridine and [3H]uracil were not observed. A comparison of the rate of catabolism of [5-3H]-uridine, [5-3H]cytidine and [6-3H]thymidine showed that cytidine is degraded in the organism 25 times more slowly than uridine or thymidine. The biological half lives for the total degradation of the [3H]nucleosides to 3H2O, based on the values in the plasma, were: uridine 1.1 h; thymidine 1.3 h; cytidine 25 h. Furthermore, the turnover time of exogenous uridine in the plasma was found to be 9 min, which gives a half life of 6 min for the metabolism of exogenous uridine to uracil.