A low molecular weight heparin in hemodialysis

Summary The purpose of our study was to check whether the dosage recommended for the low molecular weight heparin tested here, i.e., 50% of the corresponding unfractionated heparin dose, is adequate to prevent clot formation in the extracorporeal system. Sixteen dialysis treatments of 4–5 h were given to each of six chronic dialysis patients. In dialyses 1, 2, 15 and 16 unfractionated heparin (initial dose 35 IU/kg, continuous dose 20 IU/kg/h) was given, and in dialyses 3–14 low molecular weight heparin (initial dose 17.5 anti-Xa U/kg, continuous dose 10 anti-X U/kg/h). At these dose levels of low molecular weight heparin, clot formation occurred in the extracorporeal system in five of the six patients, despite the fact that the plasma anti-Xa level of 0.5 U/ml recommended by the manufacturer had been attained. For this reason the continuous dose of low molecular weight heparin had to be raised to approx. 80% of the corresponding continuous dose of unfractionated heparin. A plasma anti-Xa level of 0.7 U/ml is necessary to prevent extracorporeal clot formation.Abbreviations anti-Xa U Anti-factor Xa unit - aPTT Activated partial thromboplastin time - AT III Antithrombin III - IU International unit - LMWH Low molecular weight heparin - UFH Unfractionated heparin     

gamma-Aminobutyric acid and taurine release in the striatum of the rat during hypoglycemic coma, studied by microdialysis

Extracellular levels of striatal gamma-aminobutyric acid (GABA) and taurine were monitored during insulin-induced hypoglycemia using microdialysis. At the onset of isoelectricity in the electroencephalogram (EEG), a transient 5-fold increase in the levels of GABA occurred. Taurine levels increased 5 min following the onset of isoelectricity and continued to increase during the entire isoelectric period. The results demonstrate that events associated with the onset of isoelectricity during hypoglycemia trigger an increase in extracellular concentrations of GABA and taurine. The discrepancy in time-course of these changes may reflect differences in compartmentation, function and metabolism of the two amino acids.     

Quantitative displacement of blood acid base equilibrium in acutely water depleted dogs

Summary Dogs were water depleted 2% of their body weight by the intraperitoneal injection of a hyperosmotic solution of saline and glucose (550 mOsm/l). During a 3-h experiment these water-depleted (WD) animals showed a significant decrease in blood pH, base excess (BE) and plasma bicarbonate (Bic_p) and an increase in both hematocrit (Ht) and blood buffer capacity (BBC). These changes were quantitatively time-dependent. The rate change of pH, BE, and Bic_p were –0.072 units h^–1, –4.7 mEq/l h^–1, and 2.9 mEq/l h^–1, respectively. As control dogs showed no significant time-dependent changes in their blood acid-base status, the observed modifications in the experimental dogs were ascribed to water depletion. Increased endogenous acid production related to tissue hypoxia is suggested to be the mechanism that could explain the increased fixed acid accumulation observed in the water-depleted animals.     

Morphologic evaluation of the liver in hereditary angioedema patients on long-term treatment with androgen derivatives

17 alpha-Alkylated androgens are highly effective in preventing attacks in HAE patients. These drugs, however, seem to be implicated in the development of cholestatic jaundice, peliosis hepatis, and liver tumors. In order to assess the risk-benefit balance of the long-term therapy with androgen derivatives, a follow-up investigation was performed in 13 HAE patients. The results of this study indicate that long-term treatment (15 to 47 mo) with low doses of danazol or stanozolol does not induce significant hepatic damage detectable by laboratory tests or liver biopsy. However, the limited number of patients, although in a rather long period of observation, still suggests a careful control and the use of minimal effective doses.     

Interpretation of gas-blood ratio inP O 2polarography

Summary The differences inP _{O 2}readings between gas and blood were studied with a Clark-type electrode in the range of 38.5 to 713 mm HgP _{O 2}.The tonometered blood samples were taken in two different ways. The results showed that the gas-blood ratior _b(equilibrating gasP _{O 2}reading/equilibrated bloodP _{O 2}reading) depended not only on the sampling method but also on theP _{O 2}range: it varied from 1.005 to 1.032 for aP _{O 2}of 96.5 mm Hg, and from 1.040 to 1.081 for aP _{O 2}of 713 mm Hg according to the sampling procedure.A theoretical analysis demonstrated that the variation ofr _bwith the bloodP _{O 2}can be attributed to the influence of the degree of oxygen saturation of the hemoglobin on theP _{O 2}gradient existing in the blood diffusion boundary layer adhering to the electrode membrane.This work was supported by grants from the High Authority of the European Coal and Steel Community and from the Fonds de la Recherche Scientifique Médicale, Belgium.     

On the interaction between phenytoin and digoxin

Summary An open, randomized, single-blind cross over trial to investigate phenytoin-digoxin interactions at steady state was performed in 6 healthy male volunteers. Coadministration of phenytoin caused a significant reduction in the elimination half-life of digoxin from 33.9 to 23.7 h and a diminution in AUC_0–48 from 31.6 to 24.4 ng · ml^–1 · h. Renal digoxin clearance was not significantly altered from 135.7 to 120.3 ml · min^–1. Assuming no change in -acetyldigoxin absorption, the in decrease time-course the serum digoxin concentration was due to a significantly increased total digoxin clearance from 258.6 to 328.3 ml · min^–1. An insignificant reduction in the digoxin distribution volume from 749.4 to 668.0 l was also observed. No relevant change in the pharmacokinetic parameters (elimination half-life, area under the serum concentration time-curve, protein binding) of phenytoin was observed when phenytoin and digoxin were co-administered. The data suggest that with this drug combination the serum digoxin concentration should be carefully monitored and, if necessary, the daily digoxin dose should be increased.     

The Current Status and Future of the Artificial Kidney

The use of the artificial kidney can presently be extended to almost all patients with end-stage renal failure. To reduce the cost of treatment, technological choices have to be made. These are always a compromise between cost and adequacy. The liberty obtained by technical improvements to perform a dialysis "à la carte," depending on patient and doctor wishes, is one of the main characteristics of the present status of hemodialysis.     

Inhibition of brain acetylcholine biosynthesis by methyldopa in spontaneously hypertensive rats

The formation of 3H-acetylcholine was measured in several brain regions of spontaneously hypertensive (SH) rats following intracerebroventricular injection of 3H-choline. Endogenous acetylcholine (ACh) also was measured and specific activity-time curves for brain ACh generated for control SH rats and for SH rats pretreated with methyldopa (100-200 mg/kg, IV). The relative turnover rates for ACh in several brain regions was estimated from the specific activity-time curves. The turnover rates of ACh in rostral hypothalamus, caudal hypothalamus, medulla oblongata and pons were reduced by 34-54%. Apparently synthesis was inhibited also since methyldopa produced relatively little effect on ACh levels. More rostral brain regions, thalamus-septum, midbrain and striatum, were not significantly affected by methyldopa. Methyldopa also reduced arterial pressure by 53/28 mmHg. The ability of methyldopa to inhibit the function of cholinergic neurons in selective brain regions may be responsible for its common "anticholinergic" side effects. Since centrally-acting anticholinergic drugs reduce arterial pressure in SH rats, it is possible that inhibition of brain ACh synthesis by methyldopa also may contribute to its antihypertensive action in experimental genetic hypertension.     

Perioperative Cefamandolprophylaxe bei aortocoronaren Bypass-Operationen Serumkonzentrationsverlauf während der extrakorporalen Zirkulation

Zusammenfassung Eine perioperative antibiotische Kurzprophylaxe mit 2 g Cefamandol intravenös bei Narkoseeinleitung wurde bei 12 Patienten während coronarchirurgischer Eingriffe unter Verwendung der Herz-Lungen-Maschine durchgeführt. Bei Beginn der extrakorporalen Zirkulation (= EKZ) kam es infolge Hämodilution zu einem Absinken der Serumkonzentrationen von 110,96 ± 40,29 mcg/ml auf 70,89 ± 34,65 g/ml innerhalb von 10 min. Im weiteren Verlauf der EKZ war der Abfall der Serumspiegel gleich schnell wie davor und danach. Nach 240 min fanden sich noch Serumspiegel von 16,80 ± 9,32 g/ml. Als Ursache für das Versagen einer antibiotischen Prophylaxe kommt bei einer Operationsdauer von mehr als 4 h das Absinken der Serumspiegel unter die minimale Hemmkonzentration der entsprechenden Keime in Frage.

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Perioperative cefamandole prophylaxis in aortocoronary bypass operations: Course of serum concentration during extracorporeal circulation

Summary Antibiotic prophylaxis with 2 g Cefamandole at induction of anaesthesia was performed in 12 male patients undergoing aortocoronary bypass surgery. Caused by hemodilution, there was a marked decrease of serum concentration at the beginning of extracorporeal circulation, from 110.96 ± 40.29 mcg/ml to 70.89 ± 34.65 mcg/ml within 10 min. During extracorporeal circulation, elimination was as fast as before and after perfusion. 240 min after application, mean serum concentrations of 16.80 ± 9.32 mcg/ml were measured. Failure of antibiotic prophylaxis in operations exceeding 4 h might be due to unadaequate antibiotic concentrations, beyond the minimal inhibitory concentration for the pathogens, reported to cause infections after cardiac operations.