F. Scheler

Arteriovenous haemofiltration: A new and simple method for treatment of over-hydrated patients resistant to diuretics

ZusammenfassungUnter Ausnutzung des arteriovenösen Blutdruckgradienten wurden überwässerte Patienten, bei denen eine Ausschwemmung mit Diuretika nicht mehr zu erreichen war, mit einem Kapillarhämofilter entwässert. Mit einer Blutperfusionsrate von 100 ml/min lag die Ultrafiltrationsrate bei 200–600 ml/h und konnte bis zu 48 h ohne Wechsel des Hämofilters aufrechterhalten werden. Der besondere Vorteil der arteriovenösen Hämofiltration liegt in der einfachen Handhabung für den Arzt und dem geringen Risiko für den Patienten im Vergleich zur maschinellen Hämofiltration. Eine technische Investition ist nicht erforderlich. Auch bei Blutdruckwerten um 60 mm Hg ist eine negative Flüssigkeitsbilanz möglich.SummaryFluid withdrawal in over-hydrated patients resistant to diuretics was obtained by means of a capillary haemofilter, using the arterio-venous pressure gradient for blood perfusion at a rate of 100 ml/min. The ultrafiltration rate was 200–600 ml/h and could be maintained as long as 48 h without changing the haemofilter. This method, which needs no technical investment, is easy and simple to handle for the physician, bears only a very low risk for the patient, and ensures a negative fluid balance even at a mean blood pressure of only 60 mm Hg.

Selective removal of low density lipoproteins (LDL) by precipitation at low pH: First clinical application of the HELP system

SummaryThe first clinical application of a new extracorporeal procedure (HELP) for the selective elimination of low-density lipoproteins by heparin precipitation at acid pH is described. Plasma, obtained by filtration of whole blood through a 0.2 µ filter, is continuously mixed with an equal volume of an acetate buffer (pH 4.85) containing heparin. After removal of the precipitated heparin complex by filtration, excess heparin is adsorbed to a specially developed filter and the clear plasma filtrate is subject to bicarbonate dialysis/ultrafiltration to restore physiologic pH and remove excess fluid. The calculated efficiency for the elimination of low-density lipoproteins from plasma by HELP is 100% and is therefore comparable to conventional plasmapheresis. The HELP system shows a high degree of specificity with over 80% of total protein being returned to the patient. Over 130 treatment procedures have now been performed. Patient compliance and acceptance have been excellent and no major complications have been observed.

Plasma Lipids Are Not Oxidized during Hemodialysis

Lipid peroxidation products, both lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS) were determined in the plasma of 31 uremic patients treated with maintenance hemodialysis. Whereas patients had significantly elevated TBARS compared to 93 healthy controls (4.25 +/- 1.53 vs. 1.66 +/- 0.50 mumol/l; p < 0.01) lipid hydroperoxides were not detected in the plasma of patients before dialysis. After hemodialysis, a slight increase in TBARS was observed (4.50 +/- 1.97 mumol/l, p > 0.01). However, when the TBARS were corrected for hemoconcentration by relating TBARS to the plasma cholesterol concentrations a statistically significant decrease of TBARS was observed (1.02 +/- 0.63 mumol TBARS/mmol cholesterol vs. 0.84 +/- 0.60 mumol TBARS/mmol cholesterol; p < 0.01) after 240 min of hemodialysis. There was no evidence for the formation of plasma lipid hydroperoxides in the extracorporeal circulation. It is therefore suggested that elevated TBARS in chronic renal failure are not caused by the dialysis therapy.

Isolation and structural analysis of the circulating human cardiodilatin (alpha ANP)

SummaryA new method was applied to isolate a polypeptide hormone from human blood. The polypeptides from 1,000 1 of hemofiltrate with a molecular weight lower than 20 kDaltons were adsorbed to 2.5 kg alginic acid, then eluted, precipitated, and desalted on a G-25 Sephadex column, thus obtaining a crude lyophilised plasma polypeptide extract. These polypeptides were further submitted to ion-exchange chromatography. Thereafter, two steps of HPLC were carried out to purify a distinct polypeptide which was the circulating form of cardiodilatin (CDD) in this case. The amino acid analysis, C-terminal enzymatic cleavage by carboxypeptidase A, and sequence analysis showed that the only form of circulating cardiodilatin is the 28 amino acid residue containing molecule, cardiodilatin-99-126 cleaved from the C-terminus of cardiodilatin-126 and identical with alpha-ANP (alpha atrial natriuretic polypeptide). Other bioactive molecular forms of the polypeptide hormones of the cardiodilatin family were not detected in the hemofiltrate. The isolation procedure was followed up by a bioassay using in vitro vascular smooth muscle relaxation.

Alpha-1-Mikroglobulin in Urin und Serum bei Proteinurie und Niereninsuffizienz

SummaryAlpha-1-microglobulin (alpha-1-m) is a low molecular weight glycoprotein (mw 25–33 KD) that is filtered through the glomeruli and reabsorbed in the proximal parts of the renal tubules where it is catabolized. Normal ranges were established for alpha-1-m (100 healthy controls) in serum (20–42 mg/l) and urine (3.5–8 mg/l). Alpha-1-m was then measured in 341 urine samples whose protein pattern had been classified as “pathologic” and “normal” according to microelectrophoresis. Increased alpha-1-m concentrations were found in 266 out of 280 pathologic urines (5% false negative) and in 3 out of 61 normal urines (4% false positive). Beta-2-microglobulin (beta-2-m), total protein or protein test strips showed a poorer correlation to the electrophoretic results. Measurement of alpha-1-m is, therefore, the most sensitive of these methods for the detection of proteinuria. In 90 patients with low molecular weight proteinuria and either with or without renal insufficiency alpha-1-m concentrations were determined in both urine and serum. While all patients had elevated urinary alpha-1-m concentrations, increased serum values were only found in renal insufficiency (Ccrea<100 ml/min). Independently of these results, we were also able to establish that increased alpha-1-m levels are found at decreased glomerular filtration rates (Ccrea <70 ml/min). Pathologic alpha-1-m concentrations therefore only allow the conclusion of isolated tubular impairment when the GFR is greater than 70 ml/min. Data from 350 patients with various renal and hypertensive diseases showed that serum alpha-1-m is a more sensitive indicator of renal insufficiency, even in the so-called “creatinine blind” range (60–100 ml/min) of the GFR than either creatinine or beta-2-m.

Anwendung von niedermolekularem Heparin bei Hämodialysepatienten

Low-molecular-weight (LMW) heparin has been compared to standard unfractionated (UF) heparin in a total of 49 patients on hemodialysis and hemofiltration in order to determine the necessary therapeutic dose and its effect on the coagulation system. A LMW heparin dose corresponding to 50% of the normal UF heparin dose was found to produce similar plasma heparin levels (anti-FXa-U/ml) in particular on minimal heparinization. At higher doses, UF heparin produced a more marked increase in plasma-heparin than did LMW heparin. Highly significant differences were found between UF and LMW heparin in their effects on PTT and thrombin time. Partial thromboplastin time (PTT) increased under UF heparin by an average of 120 s whereas LMW heparin only produced an increase of 5-7 s. Thrombin time was increased by 250-280 s under UF heparin and by 5-8 s under LMW heparin. With this LMW heparin dose of 50% of the UF heparin dose, no thrombosis of the extracorporal system occurred and no macroscopic detectable thrombotic material was found in the dialyzers or filters. No significant differences were observed between the effects of UF and LMW heparin on Factor VIII activity and fibrin monomers, so that a difference in coagulation activation between the two heparins can be excluded. Furthermore, there were no changes in thromboplastin time according to Quick, fibrinogen, antithrombin III, plasminogen, and a2-antiplasmin.(ABSTRACT TRUNCATED AT 250 WORDS)SummaryLow-molecular-weight (LMW) heparin has been compared to standard unfractionated (UF) heparin in a total of 49 patients on hemodialysis and hemofiltration in order to determine the necessary therapeutic dose and its effect on the coagulation system. A LMW heparin dose corresponding to 50% of the normal UF heparin dose was found to produce similar plasma heparin levels (anti-FXa-U/ml) in particular on minimal heparinization. At higher doses, UF heparin produced a more marked increase in plasma-heparin than did LMW heparin. Highly significant differences were found between UF and LMW heparin in their effects on PTT and thrombin time. Partial thromboplastin time (PTT) increased under UF heparin by an average of 120 s whereas LMW heparin only produced an increase of 5–7 s. Thrombin time was increased by 250–280 s under UF heparin and by 5–8 s under LMW heparin. With this LMW heparin dose of 50% of the UF heparin dose, no thrombosis of the extracorporal system occurred and no macroscopic detectable thrombotic material was found in the dialyzers or filters. No significant differences were observed between the effects of UF and LMW heparin on Factor VIII activity and fibrin monomers, so that a difference in coagulation activation between the two heparins can be excluded. Furthermore, there were no changes in thromboplastin time according to Quick, fibrinogen, antithrombin III, plasminogen, and a2-antiplasmin. Thus effective Anti-FXa levels and by similar antithrombotic activity, LMW heparin will probably present less of a bleeding risk because of its reduced effect on PTT and thrombin time. LMW heparin therefore appears to be a good alternative to UF heparin for patients with renal insufficiency requiring dialysis. LMW heparin is indicated in particular in patients at bleeding risk, with diabetic retinopathy, on therapy with oral anticoagulants or platelet aggregation inhibitors, and with thrombocytopenia.

Increased ammonia production during forearm ischemic work test in McArdle's disease

SummaryA patient with typical features of late onset McArdles disease is described. During forearm ischemic work test the patient exhibited an exaggerated increase in ammonia release, largely exceeding normal values. It is suggested, that this is due to an activation of the myokinase/myoadenylate deaminase pathway. Besides lack of lactate release increased ammonia release during ischemia may be a typical feature of McArdles disease.ZusammenfassungEs wird ein Patient mit einem typischen “late onset” McArdle-Syndrom beschrieben. Während ischämischer Arbeit fand sich bei dem Patienten ein exzessiver Anstieg des Ammoniaks im Plasma. Dies dürfte auf einer Aktivierung der Myokinase/Myoadenylat-Deaminase-Reaktionen beruhen. Neben dem charakteristischerweise fehlenden Laktatanstieg unter ischämischer Arbeit scheint eine vermehrte Ammoniak-Freisetzung für das McArdle-Syndrom typisch zu sein.

Untersuchungen zur enteralen Resorption vonβ-Methyldigoxin

SummarySerum concentrations of3H-β-methyldigoxin after oral and intravenous administration (infusion) were compared in normal individuals by the application of two pharmacokinetic models. The half-life of 22 minutes for the enteral absorption obtained by the applied statistical methods reflect an unusually rapid entry of the glycoside into the organism. The intestinal absorption of3H-β-methyldigoxin is almost complete, as evidenced by nearly identicalc0-values in both compartments after oral and intravenous administration. The half-life of approximately 20 hr for the elimination from compartment II indicates rapid excretion of the glycoside.ZusammenfassungAnhand zweier pharmakokinetischer Modelle wurde bei bei gesunden Probanden eine vergleichende Analyse des Konzentrationsablaufs von3H-β-Methyldigoxin imSerum nach oraler und intravenöser Gabe (Infusion) vorgenommen. Die mit den verwendeten Auswertungsmethoden berechnete Halbwertszeit von 22 min für die Überführung3H-β-Methyldigoxin in den Organismus entspricht einer ungewöhnlich raschen Glykosidinvasion nach oraler Gabe. Aus den fast identischenc0-Werten in beiden Kompartimenten nach oraler und intravenöser Gabe geht eine nahezu vollständige Resorption hervor. Die Halbwertszeit von etwa 20 h für die Elimination aus Kompartiment II läßt einen raschen Glykosidschwund aus dem Organismus erkennen.

Dialysance und prozentuale Elimination verschiedener Herzglykoside während der Hämo- und Peritonealdialyse

SummaryPer cent elimination and dialysance of3H-gstrophanthin,3H-methyldigoxin,3H-peruvoside and3H-digitoxin were studied during regular haemodialysis using the Ultraflo-145 coil. Similar to renal clearance, dialyscance showed a negative correlation to serum protein binding of the cardiac glycosides. Per cent elimination by the dialyser was about 30–50% of the normal renal excretion of the drugs under identical conditions. Peritoneal dialysis was much less effective. It is concluded from this study that the loss of cardiac glycosides by the intermittent haemodialysis is so small that it does not need to be taken into consideration, when digitalising an anuric patient. For the treatment of severe digitalis intoxication, however, haemodialysis may be recommended.ZusammenfassungDie prozentuale Ausscheidung und die Dialysance von3H-g-Strophanthin,3H-Methyl-Digoxin,3H-Peruvosid und3H-Digitoxin wurden während der regulären Hämodialyse (Ultraflo-145-Spule) gemessen. Zwischen der Größe der Dialysance und der Serumeiweißbindung der Herzglykoside fand sich ähnlich wie bei der renalen Clearance dieser Substanzen eine negative Korrelation. Die prozentuale Elimination durch den Dialysator betrug etwa 30–50% der normalen renalen Ausscheidung der Medikamente unter identischen Versuchsbedingungen. Die Eliminationsleistung der Peritonealdialyse war wesentlich geringer. Aus den Untersuchungsergebnissen wurde die Schlußfolgerung gezogen, daß der „Glykosidverlust“, der durch die intermittierende Hämodialysebehandlung entsteht, nur etwa 1/14 der normalen Elimination beträgt und daher bei der „Digitalisierung“ eines anurischen Patienten nicht berücksichtigt zu werden braucht. Andererseits kann aber die Hämodialyse für die Behandlung schwerer Digitalisintoxikationen empfohlen werden.

Membranoproliferative glomerulonephritis with partial lipodystrophy: discordant occurrence in identical twins.

ZusammenfassungBei einer Patientin mit membranoproliferativer Glomerulonephritis und partieller Lipodystrophie konnte ein Mangel an C3 und C3-Aktivator bei normalem C4 nachgewiesen werden, sowie das Vorkommen des nephritogenen Faktors, vermehrte Fibrinspaltprodukte und eine unselektive Proteinurie.Der Verlauf der Glomerulonephritis wird durch eine erhebliche Infektneigung kompliziert (anfangs Windpocken, Tonsillitis, Masern, später Pneumonie, Meningitis, Encephalitis und Hepatitis).Wegen des nephrotischen Syndroms und beginnender Niereninsuffizienz wurde eine Cytostatika-Therapie begonnen, worauf zwar der C3-Gehalt anstieg, der Verlauf der Krankheit jedoch nicht beeinflußt wurde.Da die Patientin eine gesunde eineiige Zwillingsschwester ohne Lipodystrophie hat, die keine Verminderung der C3-Aktivität und keinen nephritogenen Faktor aufweist, beweist der vorliegende Fall, daß diese Krankheiten erworben und nicht genetisch determiniert sind.SummaryThe course of disease of a patient with membranoproliferative glomerulonephritis and partial lipodystrophy is described. The case is further characterized by a deficiency of C3 and of C3-activator, by normal values of C4, by evidence of the nephritogenic factor, by raised fibrin degradation products and by an unselective proteinuria.The course of the glomerulonephritis runs parallel to a pronounced susceptibility to infection (at first varicella, tonsillitis and measles, later pneumonia, meningitis, encephalitis and hepatitis).On account of a nephrotic syndrome and an initiative impairment of the renal function, a cytostatic treatment was begun, which although raising the C3 level, did not influence the further course of the disease.As the patient has a healthy identical twin sister without lipodystrophy, who shows no reduction in C3 and no nephritogenic factor, this case proves that these diseases are acquired and not genetically determined.