K. Schaefer

Influence of Diphenylhydantoin and Phenobarbital on Intestinal Calcium Transport in the Rat

In vitamin D deficient rats the influence of diphenylhydantoin (DPH) and phénobarbital (PB) pretreatment on intestinal uptake of 45calcium and on the activity of CaBP was studied. The DPH rats show in contrast to the PB and control rats a significantly reduced intestinal uptake of 45calcium. However, the activity of CaBP was similar in all investigated groups. These results suggest a possibly special effect of DPH on the development of the calcium and bone disorders that have been observed in patients treated with anticonvulsant drugs.

Serum 25-Hydroxycholecalciferol in Uremia

Serum 25-hydroxycholecalciferol (25-OH-D3) was determined in 20 normal persons and in 50 patients with renal failure. Low serum levels were found in patients with markedly impaired renal fu

Different Handling of Beta2-Microglobulin during Hemodialysis and Hemofiltration

Very recently it was reported that the amyloid associated with chronic hemodialysis contains, as a major component, a new form of amyloid fibril protein which is homologous to beta 2-microglobulin. As beta 2-microglobulin has a molecular weight of 11,600 daltons, investigations were carried out to see whether or not this protein would be handled differently by hemodialysis and hemofiltration, because the latter method especially is capable of eliminating solutes with such a high molecular weight. The results clearly indicate that hemofiltration removes substantial amounts of beta 2-microglobulin (about 190 mg per treatment, which represents 80% of daily production). It remains to be clarified whether or not hemofiltration is therefore superior to hemodialysis with regard to amyloid deposit formation.

INTESTINAL ABSORPTION OF VITAMIN D3 IN EPILEPTIC PATIENTS AND PHENOBARBITAL‐TREATED RATS*

The intestinal absorption of radioactive cholecalciferol was studied in patients who had been treated for years with anticonvulsant drugs and in pheno‐barbital‐treated rats. The aim of the study was to elucidate whether or not the bone changes in patients could be caused by a decreased uptake of vitamin D. The data obtained in humans and animals demonstrate that epileptic drugs do not interfere with the intestinal uptake of the vitamin. Previously reported alterations in the metabolism of cholecalciferol during anticonvulsant therapy were therefore probably due to enhanced hydroxylation of vitamin D in the liver rather than to a diminished body pool of vitamin D.

Hypercalcemia and elevated serum 1,25-dihydroxyvitamin D3 in a patient with hodgkin's lymphoma

SummaryA 74-year-old woman was hospitalized because of decreased appetite, fatigue, and weight loss. The laboratory examination revealed hypercalcemia, a slightly increased serum creatinine level, and a markedly elevated serum level of 1,25-dihydroxyvitamin D3. The most important finding the physical examination revealed was enlarged inguinal lymph nodes. A biopsy disclosed lymphocyte-depleted Hodgkins disease. After steroids, but not after calcitonin, both the elevated calcitriol concentration and serum calcium normalized. In spite of intensive chemotherapy, a further episode with hypercalcemia occurred and increased 1,25-dihydroxyvitamin D3 serum levels were observed. According to the available evidence it seems probable that the humoral hypercalcemia in this patient resulted from production of 1,25-dihydroxyvitamin D3 in the tumor.

Influence of phenobarbital and diphenylhydantoin on vitamin D metabolism and calcium retention in rats.

SummaryThe metabolism and the organ distribution of double-labelled vitamin D3 (1,2-3H-4-14C-cholecalciferol) has been investigated in rats receiving either phenobarbital (PB) or diphenylhydantoin (DPH). Whereas the DPH-treated rats showed a metabolic pattern and organ distribution comparable to the control animals, the PB-treated rats had a greater amount of radioactivity (mainly as 25-Hydroxycholecalciferol) in their serum at 3 days, and at 10 days they showed a reduced concentration of radioactivity in their liver and kidney. As the retention of47calcium was not only decreased in the PB-group but as well in the DPH-group, which showed an almost normal handling of the injected vitamin D3, it remains speculative, as to whether or not the PB-induced alterations in the metabolism of vitamin D are responsible for the reported occurence of osteomalacic bone disease in patients treated by anticonvulsants.ZusammenfassungEs wurden der Stoffwechsel und die Organverteilung von doppelt-markiertem Vitamin D3 (1,2-3H-4-14C-Cholecalciferol) an Ratten untersucht, die entweder mit Phenobarbital (PB) oder Diphenylhydantoin (DPH) behandelt waren. Während die DPH-behandelten Ratten ein Stoffwechselmuster und eine Organverteilung ähnlich den Normaltieren aufwiesen, hatten die mit PB behandelten Ratten am 3. Untersuchungstag eine höhere Konzentration von 25-Hydroxycholecalciferol im Serum und am 10. Tag der Untersuchung eine im Vergleich zu den Normaltieren und DPH-Ratten erniedrigte Radioaktivität in der Leber und Niere. Da jedoch die Calcium-Retention nicht nur in der PB-Gruppe, sondern auch in den DPH-Tieren erniedrigt gefunden wurde, kann derzeit noch nicht entschieden werden, ob die bei Epilepsiekranken nachweisbaren vorwiegend osteomalacischen Knochenveränderungen durch eine Störung des Vitamin D-Stoffwechsels verursacht werden.

Digoxin-quinidine interaction in patients with renal failure

SummaryInvestigations were performed in order to study whether or not quinidine would exert similar effects on the serum digoxin concentration in patients with renal failure as in normal subjects. Fourteen out of fifteen patients showed a significant increase of the serum digoxin level after four days of quindine application. This indicates, that the quinidine effect is not solely caused by a decrease of the renal digoxin clearance, although nine patients, not being hemodialysed, revealed a correlation between their creatinine clearance and the rise of the serum digoxin concentration after quinidine. As however, the patients on hemodialysis did not show higher digoxin levels than those treated conservatively, it is suggested that the degree of the uremic intoxication might be responsible for the observed correlation.ZusammenfassungEs wurden Untersuchungen durchgeführt, um festzustellen, ob Chinidin bei Nierenkranken den gleichen Effekt auf den Digoxinserumspiegel zeigt wie bei Gesunden. Vierzehn von fünfzehn niereninsuffizienten Patienten wiesen einen signifikanten Anstieg des Digoxinspiegels nach viertägiger Chinidinbehandlung auf, was zeigt, daß diese Chinidinwirkung nicht nur durch eine Verminderung der renalen Digoxinclearance hervorgerufen wird. Obwohl neun nicht dialysepflichtige Patienten einen Zusammenhang zwischen Kreatininclearance und Anstieg des Digoxinspiegels aufwiesen, ist anzunehmen, daß der Grad der urämiebedingten Intoxikation für den beobachteten Zusammenhang verantwortlich zu machen ist, da die hämodialysierten Patienten keinen höheren Digoxinanstieg im Serum zeigten als die konservativ behandelten Patienten.

Good Biocompatibility of the Polyamide Hemofilter

Chronic hemofiltration (HF) is now a well-established method, especially for elderly uremic patients and those suffering from cardiovascular problems. This is due to the fact that chronic HF offers superior treatment comfort with less hypotensive episodes, vomiting, muscle cramps and febrile reactions. Apart from the different blood purification techniques involved in chronic HF compared to hemodialysis (i.e. convection versus diffusion), it might well be that the better treatment comfort is attributable to a certain extent to the polyamide HF membrane used in our HF treatments. We studied different biocompatibility parameters and received the following data: (a) leukocytes and thrombocytes remained unchanged during a treatment session; (b) elastase increased slightly but there was no difference between the polyamide and polycarbonate membrane, and (c) arterial and venous concentrations of C5a and C3d remained almost unchanged. The superior treatment comfort and better vascular stability of HF over hemodialysis might also be due to the improved biocompatibility of the applied hemofilter as the polyamide membrane induces no changes in different biocompatibility parameters such as leukocytes, thrombocytes, C5a or C3d.

Comparison of Drug Elimination by Current Methods of Blood Purification

Drug elimination by extracorporeal methods (hemodialysis, hemoperfusion, hemofiltration, plasmapheresis) was investigated in an ex vivo model using banked blood. The drugs (cefotaxime, glibenclamide,

The Metabolic Fate of (26,27) 3H-25-Hydroxyvitamin D3 in Normal, Uremic and Rachitic Rats

Abstract. Investigations on the metabolism of 3H‐25‐HCC have been performed in normal rats as well as in uremic, rachitic and rachitic‐uremic animals. The metabolic pattern of the uremic rats differs from that obtained in the control group in so far as uremic rats retain more of the injected radioactivity as peak IV (25‐HCC), whereas the normals have converted more into the peak V fraction. The results obtained in the rachitic group are completely different, as these animals have formed a rather high amount of peak I, a metabolic fraction which is considered to be an ester or other conjugate of 25‐HCC. Rachitic‐uremic rats show a metabolic pattern similar to the normal and uremic rats. These results suggest that a condition of uremia “normalizes” is some way the enzymatic disturbances provoked by a state of severe rickets.