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Die Wechselwirkung zwischen Chinidin und Digoxin hat fur die Digitalistherapie grose klinische Bedeutung erlangt [1, 2, 4, 7, 8]. Der von verschiedenen Arbeitsgruppen beobachtete Anstieg des Serumdigoxinspiegels unter Chinidin war nach Untersuchungen von Leahey et al. (1979) mit einer verstarkten kardialen Wirkung des Digoxins und in Einzelfallen auch mit der Gefahr einer Digitalisintoxikation verbunden [2, 7, 8].

Despite progress in intensive therapy and dialysis the lethality of postoperative acute renal failure (ARF) remains very high. Between 1958 and 1976, 374 out of 11474 patients treated in the intensive care unit developed ARF. By conservative treatment that is described in detail, the mortality was reduced from 80 percent (up to 1972) to 50 percent. The mortality rate of dialysis was 86 percent (85 of 98 patients). ARF reflects the severity of the illness of these patients. The prognosis depends besides further complications on the administration of optimal intensive care and early dialysis.

After full digitalisation, 11 healthy subjects received 0.375 mg digoxin daily as maintenance dose. Under steady-state conditions and determination of serum concentration and renal clearance of digoxin, they were then given 500 or 1000 mg quinidine daily in addition to the digoxin. While serum concentration of digoxin rose significantly from 0.75 +/- 0.2 ng/ml after one week on 500 mg quinidine, and to 1.8 +/- 0.6 ng/ml after 1000 mg of quinidine, renal digoxin clearance fell from 186.2 +/- 67.4 to 125.4 +/- 61.8 ml/min after 500 mg of quinidine. Raising quinidine dosage to 1000 mg daily caused no further digoxin clearance reduction. During the total experimental period endogenous creatinine clearance remained unchanged. The results indicate that the rise in serum digoxin concentration on simultaneous quinidine administration is largely due to reduction in renal digoxin clearance. A clinical observation confirms the considerable practical importance of this interaction.

Four cases of hemolytic-uremic syndrome (HUS) are presented in which light and electron microscopic examination of renal biopsies (2 cases) and light microscopic examination of the kidneys on autopsy material (2 cases) revealed no changes reflecting microangiopathy. Based on these findings and on personal observation of 197 cases of HUS with glomerular or vascular changes, it is considered questionable whether the results of animal experiments by Brain et al. [1962] and Brian and Brain [1968] can be transferred to man. The cause of hemolytic anemia in HUS is considered unclarified, except for cases in which hemolysis is triggered by neuraminidase-producing bacteria and viruses.

Long-term dialysis treatment of diabetics with terminal renal failure is beset with severe complications. In 19 unselected diabetics in terminal renal failure (13 juvenile diabetics and 6 maturity-onset diabetics) the clinical course during long-term dialysis was observed. A total of 1377 dialyses during 167 months of treatment were performed. Diabetic angiopathy, hypertension, and hyperhydration were the most prominent complications. The interval between the onset of diabetes and the beginning of dialysis treatment was 21,5 years in the juvenile diabetics and 5,2 years in maturity-onset diabetes. The survival time during dialysis was on average 13,2 months for the juvenile diabetics and 0,6 months for maturity-onset diabetics. The patients died chiefly from cardiovascular complications.

After six years of home haemodialysis and two years of continuous ambulatory peritoneal dialysis a 59-year-old woman developed an aluminium-induced osteopathy, myopathy and normochromic anaemia. She was at first treated with intravenous, then peritoneal, deferoxamine, 1 g every other day. Before treatment, 15.8 micrograms aluminium (Al) had been eliminated daily, with a peritoneal clearance of 0.3 ml/min; after intravenous deferoxamine a mean of 774.3 +/- 102.3 micrograms Al was eliminated per day, after peritoneal deferoxamine 646.7 +/- 89.6 micrograms of Al per day, with a peritoneal clearance of 2.2 +/- 0.9 (intravenous) and 1.9 +/- 0.7 ml/min (intraperitoneal). After four months of deferoxamine administration, mostly intraperitoneally as an out-patient, the osteomalacia clearly improved, as did the myopathy and anaemia.

With a daily maintenance dose of 0.1 mg digitoxin a mean steady state digitoxin serum concentration of 17.0 +/- 3.2 ng/ml was measured in 10 male probands. When 750 mg of quinidine bisulphate were administered at the same time digitoxin concentration increased significantly to 22.4 +/- 4.2 ng/ml (P less than 0.0005). The serum half life of digitoxin during quinidine treatment was significantly increased to 10.8 +/- 2.1 days compared to a control group with 7.6 +/- 1.6 days (P less than 0.0025). Protein binding of digitoxin, renal digitoxin excretion and renal digitoxin clearance were equally uninfluenced by quinidine as were endogenous creatinine clearance and sodium and potassium excretion in urine. In two patient with cardiac insufficiency there was likewise a significant increase in digitoxin serum concentration. For clinical application of combined therapy of quinidine and digitoxin the danger of digitalis intoxication seems to be less in comparison to digoxin as increase of digitoxin concentration in serum is lower than of digoxin.

Infektionen gehoren zu den haufigsten letalen Komplikationen nach Nierentransplantation (TR). Unsere Erfahrungen bei der Behandlung dieses Problems haben wir zusammengestellt nach 38 TR bei 37 Patienten (P.). Zusammen mit klinischen Daten wurden 1366 mikrobiologische Untersuchungen (Urin, Blut, Sputum, Wundabstriche, Dranageflussigkeit) ausgewertet. 495 Proben waren steril, 507 eindeutig pathologisch und 364 Befunde mit fraglicher Atiologie wurden nicht ausgewertet. Haufigste Grunderkrankung war eine Glomerulonephritis (n = 24). 5 Patienten wurden vor der TR bilateral nephrektomiert. Die Immunsuppression nach Transplantation (pT) erfolgte mit Azathioprin, Cyclophosphamid und Corticoiden.

Digitoxin concentration, measured by radio-immunoassay, was significantly lower in 51 patients in chronic renal failure (23.2 +/- 7.8 mug/l) than in 29 patients in heart failure (26.5 +/- 7.3 mug/l), although both groups were on the same maintenance dose of 0.1 mg daily. Despite a normal serum albumin concentration, digitoxin protein binding was less in uraemic patients than in those with normal renal function. Renal failure did not affect intestinal digitoxin absorption. In patients in chronic renal failure elimination half-time was significantly shorter (5.7 +/- 0.9 days) than in healthy controls (7.6 +/- 1.6 days). There was no significant difference in the excretion of water-soluble ("cardioinactive") digitoxin metabolites in urine between patients in chronic renal and those in heart failure. In patients with normal renal function, of dichloromethane-soluble (cardioactive) metabolites only digitoxin could be demonstrated by thin-layer chromatography. The results indicate that patients in chronic renal failure can safely be given the same dose as those with normal renal function, without danger of over- or underdosage.

Das Thema „Therapeutische Beeinflussung der Kontraktilitat in der Klinik“ stellt uns vor die Aufgabe, die wichtigsten therapeutischen Probleme zu umreisen, mit denen wir bei der Behandlung von Erkrankungen des Herzens mit kontraktilitatsbeein-flussenden Pharmaka in der taglichen Praxis konfrontiert werden. Folgende Fragen erscheinen vordergrundig: 1. Welche neuen Erkenntnisse uber die Wirkungsweise positiv oder negativ inotrop wirkender Pharmaka wurden in den letzten Jahren gewonnen, die auch fur unser therapeutisches Handeln von Bedeutung sind? 2. Ist es zu therapeutischen Entscheidungen notwendig, Kontraktilitatsparameter zu messen? 3. Welche kontraktilitatsbeeinflussenden Pharmaka werden in der Klinik hauptsachlich angewandt? Wann ist ihre Anwendung indiziert oder kontraindiziert? 4. Wo liegen die Grenzen der Indikationen zum Emsatz kontraktilitatsverandernder Pharmaka?

A Kaposi's sarcoma of the skin with nodular and follicular lesions but no visceral involvement developed in a 44-year-old man nine months after transplantation of an haplo-identical kidney (a relative as donor). He was on an immunosuppressive regimen of daily 10 mg methylprednisolone and 2.5 mg/kg cyclosporin A. No HIV antibodies were demonstrated. After reduction of the dosage to 4 mg methylprednisolone and 1 mg/kg cyclosporin A no further growth of the skin lesions was observed, while transplant function was maintained. The lesions regressed after radiation of two areas in the right lower leg with 48 Gy. Ten months later the sarcoma again progressed and required further radiotherapy, which arrested growth, while there was no change in transplant function.

64 percutaneous renal biopsies were done on 60 patients with renal impairment (serum creatinine level more than 1.5 mg%) under sonographic guidance. In 62 biopsies (96.8%), more than 3 glomeruli were seen, in 45 biopsies (70.3%) the amount of at least 10 glomeruli could be obtained, this being the amount desirable for a good histological diagnosis; 8 cases (12.5%) presented with minor complications after the biopsies. All of them resolved spontaneously. Ultrasound-guided percutaneous renal biopsy is a safe procedure for rapid diagnosis and induction of a specific therapy in patients with renal impairment.

Aluminum concentrations in the dialysate and serum of 14 patients on CAPD were measured every six months. Additionally, in ten of the patients Al elimination was measured after a bolus ingestion of 1800 mg aluminium-chloride-hydroxide-complex. There was no significant difference between serum Al concentrations initially (47.3 +/- 8.2 micrograms/l), at six months (55.4 +/- 9.5 micrograms/l), and after 12 months (44.3 +/- 10.1 micrograms/l) although the Al concentration in the dialysate had been decreased from 16.6 +/- 2.3 micrograms/l to 1.5 +/- 0.2 in the last six months. The Al concentrations in the effluent dialysate were 14.5 +/- 1.3 micrograms/l initially, 15.6 +/- 1.2 micrograms/l after six months and 11.9 +/- 2.6 micrograms/l after 12 months. During kinetic studies a constant rise of serum Al concentration was found until the fifth hour, from 29.9 +/- 2.5 to 42.5 +/- 4.0, and a decline after 24 hours to 32.4 +/- 3.0 micrograms/l. The quantity of Al eliminated was 41.1 +/- 8.7 micrograms/24 h, equivalent to 1.2% of the ingested dose. In patients with residual renal function, renal Al clearance was almost double the peritoneal one. These results indicate that Al elimination by CAPD is not efficient and ingestion of Al-containing phosphate binders can result in Al accumulation.

Since dialysis solutions in CAPD are now nearly aluminum free, the only source for elevated aluminum levels are aluminum-containing phosphate binders. Elimination with CAPD is insufficient to prevent aluminum accumulation. Therefore, we investigated a phosphate binder consisting of calcium alginate, a natural polyuronic acid, containing 100 mg calcium/g substance in 14 patients on CAPD over a period of one year. The patients had previously been treated with aluminum-containing phosphate binders for a period of 24.3 +/- 21.3 months. During a period of 3 weeks before changing to the new phosphate binder the mean (+/- SD) serum phosphorus concentration was 1.8 +/- 0.4 mmol/l, while at the end of one year of treatment with calcium alginate the concentration was 1.6 +/- 0.4 mmol/l. In order to lower serum phosphorus to this level, it was necessary to increase the mean (+/- SD) amount of calcium alginate from 6.9 +/- 1.3 g per day at the beginning of the study to 8.3 +/- 2.1 g per day at the end. The mean (+/- SD) serum calcium concentration did not change throughout the study period. Serum levels of alkaline phosphatase, 1.25 (OH)2 vitamin D3, and intact parathyroid hormone did not change as well. The mean (+/- SD) serum aluminum level declined from 36.0 +/- 20 to 14.0 +/- 11.3 micrograms/l after 6 months (p less than 0.001). In conclusion, calcium alginate is a good alternative to aluminum-containing phosphate binders and to phosphate binders on a calcium base as it does not lead to hypercalcemia. It prevents aluminum intoxication and has no serious side effects.

Combined oral therapy with digoxin (0.375 mg/dl) and disopyramide (300 and 600 mg/dl) in nine subjects did not alter steady-state digoxin serum concentrations just before the daily single digoxin dose. Digoxin and creatinine clearances were not changed. After a bolus IV dose of 0.8 mg digoxin, volume of distribution (from 672 ± 176 l to 407 ± 153 l) and elimination t½β of digoxin were reduced significantly in five subjects after 600 mg oral disopyramide daily (from 40.2 ± 11.7 hr to 22 ± 7.3 hr). Total clearance and digoxin distribution t½α did not change significantly. The clinical significance of this interaction is not clear. Clinical Pharmacology and Therapeutics (1983) 34, 176–180; doi:10.1038/clpt.1983.149

Bei der Beurteilung des Nierentransplantates spielt die Sonographie eine wichtige Rolle. Gemas der Literatur soll dies auch auf die Erkennung von Abstosungsepisoden zutreffen. Dabei werden in der Regel in der Literatur verschiedene Kriterien angegeben, insbesondere die Volumenzunahme des Organs von mehr als 20% in 5 Tagen, die Zunahme der Parenchymdicke, Schwellung der Markpyramiden, Auftreten von perirenaler Flussigkeit, Unscharfe der Parenchym-Pyelon-Grenze sowie eine Pyelonausweitung (Abb. 1).

There are still few data available about the quantitative distribution of the cardioactive metabolites of digitalis glycosides in human tissues. We therefore developed a method for the specific determination of digoxin, digitoxin, their semi-synthetic derivatives and dependent cardioactive metabolites in autopsy samples of heart and kidney. Tissue extraction and purification steps were followed by HPLC separation and RIA quantitation.

To check the reliability of the captopril test and of quantitative radioisotope techniques for the primary diagnosis of renovascular hypertension the data from 41 patients suspected of this disease were retrospectively analysed. In all cases plasma renin activity (PRA) was assayed in peripheral blood and in renal vein blood before and after 25 mg captopril. Double tracer studies with 131I-hippuran and 99mTc-DTPA were also performed, as was renal arteriography. The postoperative blood pressure plots of 23 patients with unilateral renal artery stenosis (who had subsequently been operated upon) were included in the evaluation. Renovascular hypertension was diagnosed in 21 patients and essential hypertension in 20. Twelve of the 20 patients with essential hypertension had renal artery stenosis, but this had not produced renovascular hypertension. The diagnostic significance of the tests as markers of renovascular hypertension was as follows: captopril test P less than 0.001, glomerular filtration fraction P less than 0.02, hippuran clearance P less than 0.001. The captopril test and the quantitative radioisotope techniques were in agreement in identifying patients with renal artery stenosis and renovascular hypertension. False-positive results due to methodological shortcomings can be avoided by applying both methods in succession.

SummaryA study was carried out in 10 healthy male subjects to investigate whether mofebutazone, a phenylbutazone derivative, influenced furosemide-induced diuresis and PGE, excretion as has been shown with other non-steroidal anti-inflammatory agents such as aspirin and indomethacin. The subjects received, at random, a single dose of either 40 mg furosemide or 40 mg furosemide plus 600 mg mofebutazone and were then crossed over to the other regimen after 10 days. Urine was collected for 45 minutes before and then for six 45-minute clearance periods after drug administration. Urine volumes and excretion of sodium, potassium, chloride, magnesium, creatinine and the main metabolite of PGE2were measured at the end of each period, as were blood levels of creatinine and mofebutazone from samples taken before, during and after administration. The results showed no significant differences between the two groups, indicating no interaction between mofebutazone and the diuretic.

Im Gegensatz zur Untersuchung der Resorption von Digoxin, s-Acetyl-Digoxin und s-Methyl-Digoxin, uber die in der Literatur keine wesentlichen Meinungsverschiedenheiten bestehen, ist die renale Elimination dieser Substanzen beim Menschen weiterhin ein Thema kontroverser Diskussion. Doherty (4) konnte beim Hund mit Hilfe von Mikropunktionsmethoden nachweisen, das Digoxin sowohl glomerular filtriert wie auch tubular reabsorbiert wird. Da diese Untersuchungsmethode beim Menschen nicht anwendbar ist, haben wir versucht mit Hilfe von vergleichenden Untersuchungen der renalen Clearances von Digoxin, β-Methyl-Digoxin einerseits und Inulin- wie auch Paraaminohipursaure andererseits bessere Anhaltspunkte fur den renalen Eliminationsmechanismus zu erhalten.

Die maligne Hypertonie (mH) ist definiert als klinische Umschreibung einer Bluthochdruckphase, die sich im Verlaufe einer primaren oder sekundaren arteriellen Hypertonie entwickelt oder ohne vorausgehende Hochdruckkrankheit entsteht. Der diastolische Blutdruck (RR) ist hoher als 120 mm Hg, es besteht ein Fundus hypertonicus Grad III–IV nach Keith, Wagner und es entwickelt sich eine schnell zunehmende Niereninsuffizienz (NI), die haufig in der Uramie endet, wenn nicht vorher andere todliche cerebro- oder cardiovasculare Komplikationen auftreten.

A 49-year-old previously healthy man fell gravely ill after repeatedly eating the mushroom Paxillus involutus. Haemolysis and circulatory shock caused acute renal failure, acute respiratory failure and disseminated intravascular coagulation. The patient died three-and-a-half days after the mushroom meal in protracted shock. In addition to the signs of haemolysis, post-mortem examination revealed signs of intravascular coagulopathy in lungs, kidneys, adrenals, myocardium, liver and spleen. There were also extensive fat emboli to both lungs. An IgG antibody against paxillus involutus extract was demonstrated in the patient's serum. The immunological reaction pattern suggests primarily the formation of an immune complex, which secondarily attaches itself to the erythrocyte surface and causes intravascular haemolysis by activation of the complement chain. In the first instance the diagnosis is made from anamnestic data. In addition to adequate treatment of circulatory shock, immediate plasma separation could provide a chance of effective treatment.

A 49-year-old woman took about 12.5 mg digoxin with suicidal intent. Severe arrhythmias, including recurrent ventricular fibrillation, occurred. Sheep Fab fragments of digoxin-specific antibodies were administered i. v. at a dose of 480 mg. Serum free-digoxin concentration fell within half an hour to 0, with simultaneous rise of total digoxin from 13 micrograms/l to a maximum of 176 micrograms/l after 2 hours. At the same time there was marked improvement in the clinical condition with restoration of a stable sinus rhythm. There were no side effects to the Fab fragment administration.

In a 29-year-old man with primary thrombotic-thrombocytopenic purpura a significantly increased plasma concentration of platelet-specific proteins was demonstrated as an expression of increased intravascular platelet activation and destruction during the acute phase of the disease. There was also abnormally elevated IgG loading of platelets. During administration of fresh plasma alone (total of six litres over one week) the clinical state deteriorated further into coma and failure of spontaneous ventilation. The marked thrombocytopenia and microangiopathic haemolytic anaemia remained unchanged. Only after repeated plasmapheresis was it possible to break through the acute disease process. Remission (restoration of vital functions, normalization of platelet count and haemolysis signs) was achieved after five courses of plasmapheresis with a total exchange volume of 20 litres. At least in this case, the therapeutic success of plasmapheresis argues for an immunological-toxic genesis of thrombotic-thrombocytopenic purpura.

Die Therapie der Endokarditis nach kunstlichem Klappenersatz besteht fast immer in einer Reoperation. Gezielte medikamentose Therapie mit bakteriziden Antibiotika ermoglicht meist eine Operation im fieberfreien Intervall [2]. Bei alien Endokarditisformen werden vornehmlich Antibiotika eingesetzt, die neben einer Bakterizidie eine gute Gewebegangigkeit besitzen [6].

Seventy-six patients with clinical and ECG evidence of digitalis toxicity and serum-digoxin concentrations over 2.5 ng/ml were investigated for possible correlation between certain ECG changes and the level of serum digoxin, but no correlation was found. However, radioimmunological determination of digoxin level proved to be a reliable means of deciding whether abnormalities of impulse formation or conduction were due to digitalis. In only one case (during haemodialysis) was there a fall in potassium level below normal, with signs of digitalis toxicity electrocardiographically. In five other patients with serum digoxin levels above 6 ng/ml high potassium values were found. Caution in the administration of potassium is advised: it should be given only if it is demonstrated to be below normal. Fifty-one of the patients had impaired renal function.

Bei der Behandlung schwerster Schlafmittelvergiftungen haben neben den vorrangigen Masnahmen der Intensivpflege Hamodialyse, Peritonealdialyse und forcierte Diurese einen festen Platz. Die Nachteile dieser Eliminationsverfahren, zu geringe Effektivitat der forcierten Diurese und Peritonealdialyse, personeller und apparativer Aufwand der Hamodialyse sowie die Begrenzung des Einsatzes dieser Verfahren auf Substanzen mit bestimmten pharmakologischen Eigenschaften (Fett- bzw. Wasserloslichkeit, Eiweisbildung), haben die Aufmerksamkeit auf andere Methoden zur Elimination von Pharmaka gelenkt. In Modellversuchen und bei Tieren wurden Perfusionen durch Kationen- und Anionenaustauscherharze und aktivierte Kohle vorgenommen [6]. Rosenbaum u. Mitarb. [3, 4] benutzten ungeladenes Adsorberharz XAD 2 zur Barbitalelimination bei schwer vergifteten Hunden und Patienten.