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Biomedical subjects

G Schultze

Publications and source records attributed to G Schultze.

At least 19 recordsLinked to original sources

Formation of thrombin-antithrombin III complex using polyamide and hemophan dialyzers.

The recently developed ELISA for the thrombin-antithrombin III complex (TAT) is a sensitive, specific, and simplified means of detecting intravascular coagulation. For further evaluation of the thrombogenicity of a polyamide (P) and a Hemophan (H) hollow-fibre dialyzer a cross-over study was done in ten stable patients on maintenance hemodialysis. At the same doses of heparin (mean bolus of 30 U/kg bw and maintenance doses of 86 U/kg bw), thrombin time and partial thromboplastin time were significantly lower using H. At the end of dialysis TAT was significantly higher in H (mean +/- SEM before HD 3.57 +/- .56, at 240 min 14.9 +/- 6.5 ng/ml, p less than 0.05, Wilcoxon-test) than in P (before HD 4.36 +/- .98, at 240 min 8.95 +/- 3.0 ng/ml, p less than 0.05 H 240 vs. P 240, Wilcoxon-test). Visible clotting was more pronounced in the H filter. Among other favourable features of blood compatibility the polyamide/polyvinylpyrrolidone copolymer with a hydrophilic/hydrophobic microdomain structure has less thrombogenicity. The modified cellulosic membrane H has advantages in complement activation and leukocyte depression, but thrombogenicity seems less favourable since the incorporated diethyl-amino-ethyl groups with their positive charge bind and inactivate negatively charged heparin.

Antithrombin III

[Oncogenic hypophosphatemic osteomalacia].

In the courses of six years a severe hypophosphataemic osteomalacia, painful motor impairment and multiple rib fractures developed in a 51-year-old man. The symptoms gradually improved within one year under treatment with 3 micrograms daily of 1,25-dihydroxycholecalciferol, 3 g phosphorus and 3 g calcium, and biochemical parameters and the bone scintigram became normal. Ultimately, computed tomography, scintigraphy and digital subtraction angiography revealed a highly vascularized tumour in the condylar aspect of the right femur, and it was chiselled out. Histologically it was a mesenchymal phosphaturic tumour of haemangiopericytoma type of questionable benignity. After the operation the patient was symptom-free for some weeks without any drug treatment, but the latter was then resumed because of renewed bone pain. By now, two years later, he is essentially without pain and has full mobility. However, repeat scintigraphy and angiography revealed renewed tumour growth in the right femoral condyle.

Calcitriol

Eicosanoid release as laboratory indicator of biocompatibility.

Biocompatibility evaluation of extracorporeal devices requires the establishment of sensitive indicators of blood cells/surface interactions. Among others, arachidonic acid derivatives, such as prostaglandins and thromboxanes, play an important role in the cell control systems. Hence, the release of eicosanoids during blood exposure to dialyzer membranes was investigated. Experiments included in vitro incubation of human blood with flat membranes (FM), as well as ex vivo perfusion of hollow fiber membranes (HFM) with blood from healthy volunteers in single-pass fashion. In both models, a significant release of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) was detected. In addition, the amount of eicosanoid release depended on the type of membrane tested. After a 10-min FM incubation with fresh blood, plasma concentrations of TXB2 and PGE2 were pronounced by polycarbonate when compared to Cuprophan and polyacrylonitrile. During 10 min of open loop perfusion of HFM, polymethylmethacrylate was the most active biomaterial, whereas the reactivity of Cuprophan was significantly lower. Among HFM, Hemophan was by far the less active. These results indicate that the release of eicosanoids represents a sensitive parameter of blood cells/membrane reactivity. Thus, the question arises as to whether or not the extracorporeal process of cyclooxygenase activity could contribute to the clinical side effects of chronical hemodialysis.

Biocompatible Materials

Effect of dialyzer membranes on in vitro generation of eicosanoids.

Eicosanoids are potent substances released from blood cells after contact with foreign materials. Eicosanoid generation, in addition to complement fragment formation, may be a valuable indicator of the biocompatibility of dialyzer membranes. In the present in vitro study, eicosanoid generation induced by several different flat dialyzer membranes [polyacrylonitrile (PAN), cuprammonium cellulose (CC), and polycarbonate (PC)] was evaluated and compared using blood from non-uremic healthy volunteers. Generation of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) was greatest with PC followed by PAN and CC. The formation of C3a des arg with PAN was less than with either CC or PC. Our results suggest that dialyzer membranes affect complement activation and eicosanoid generation differently; biocompatibility as expressed by a low level of complement fragment formation does not necessarily translate into biocompatibility when considering eicosanoid generation.

Acrylic Resins

The influence of long-term infusion of the calcium antagonist diltiazem on postischemic acute renal failure in conscious dogs.

The influence of long-term infusion of the calcium-entry blocker diltiazem on postischemic acute renal failure was investigated in conscious dogs monitored by implanted instruments. In 18 uninephrectomized beagle dogs on a salt-rich diet, an electromagnetic flow probe and an inflatable plastic cuff were placed around the renal artery. Acute renal failure was induced by inflating the cuff for 180 min in the conscious animal. Group A (n = 5, control) received an intraaortic injection of 0.9% NaCl (5 ml/day) from the 3rd day before until the 7th day after ischemia and group B (n = 6, posttreatment) an intra-aortic injection of diltiazem (5 micrograms X min-1 X kg-1) beginning at the end of ischemia until the 7th day. Group C (n = 7, pre- and posttreatment) received diltiazem from the 3rd day before until the 7th day after ischemia. In group A, renal blood flow dropped from 149 +/- 16 (preischemic) to 129 +/- 29 ml X min-1 on the 1st day after ischemia. In contrast, renal blood flow increased on the 1st postischemic day in both treatment groups by 29 +/- 15% (group B, P 0.05) and 14 +/- 13% (group C). In the following days, there was no significant difference in renal blood flow between groups A, B and C. In group B, the reduction of the glomerular filtration rate was similar to that in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury

Beneficial effects of long-term prostaglandin E2 infusion on the course of postischemic acute renal failure. Long-term studies in chronically instrumented conscious dogs.

The effect of a continuous intra-aortal infusion of prostaglandin E2 (PGE2) (0.03 microgram . min-1 . kg-1) on the course of postischemic renal failure (180 min cessation of blood flow by inflation of a pneumatic cuff) has been investigated in 11 conscious sodium-replete dogs. The glomerular filtration rate (51Cr-EDTA: endogenous creatinine clearance) was less decreased in the PGE2 group (group B, n = 6) than in the control group (group A, n = 5; 13 ml . min-1 vs. 22 ml . min-1; p less than 0.05). Renal blood flow (electromagnetic flow probe) was markedly lower in the control group (82 ml . min-1) than in the PGE2 group (130 ml . min-1; p less than 0.05), even exceeding baseline levels in the latter group. Accordingly, the excessive rise in renal vascular resistance in the control group (+277%) was abolished in the PGE2 group (-20%) (p less than 0.05). Nitrogen retention was also markedly improved. Plasma renin activity, which was markedly raised initially (25.8 ng angiotensin I . ml-1 . h-1) was not significantly further increased during the subsequent 7 days. Urinary excretion of PGE2 was diminished in the control group and elevated following PGE2 infusion. It is suggested that the beneficial effects of PGE2 are mediated by preservation of renal perfusion. Additional effects of prostanoids on the ultrafiltration coefficient (KF) and cytoprotection by reduction of intracellular calcium accumulation must also be taken into consideration.

Acute Kidney Injury

Does captopril reduce renal function in renovascular disease by postglomerular vasodilatation?

In hypertensive patients with bilateral renal artery stenosis (RAS) or RAS of a solitary kidney, reversible decrease of glomerular filtration rate (GFR) or acute renal failure has been observed following captopril administration. Decrease of GFR has been ascribed to preferential efferent vasodilatation. To test this hypothesis, acute changes of mean arterial pressure (MAP), renal plasma flow (RPF), GFR, plasma renin activity (PRA) and PGE2-excretion after 50 mg captopril orally were measured in post-transplant hypertensives with and without transplant renal artery stenosis (TRAS) during treatment with diuretics. The fall in MAP was similar in both groups; RPF did not change significantly; GFR decreased from 58 +/- 14 (s.d.) to 49 +/- 14 ml/min (TRAS, n = 8) and from 60 +/- 15 to 50 +/- 16 ml/min (without TRAS, n = 8). There was no evidence of postglomerular dilatation in patients with TRAS, and filtration fraction decreased only in patients without TRAS. Increase of PRA after captopril was not significantly different between the two groups. PGE2-excretion did not change significantly. In one patient with severe TRAS, long term angiotensin converting enzyme (ACE) inhibition and acute normalization of MAP with sodium nitroprusside both induced a comparable decrease of GFR. The results demonstrate that acute postglomerular vasodilatation does not necessarily occur after ACE inhibition in patients with TRAS and a high-renin state.

Captopril

Prostaglandin E2 promotes hypotension on low-sodium hemodialysis.

The influence of low-sodium dialysate (126 mmol/l) on plasma levels of prostaglandin E2 (PGE2) and PGF2 alpha, plasma renin activity (PRA) and arterial blood pressure was investigated in 16 patients on maintenance hemodialysis. PGE2 rose more than tenfold and there was a significant increase in PGF2 alpha and PRA. Mean arterial pressure dropped by 30 mm Hg causing discomfort in several patients. By contrast, conventional hemodialysis against 140 mmol/l of sodium was followed by less pronounced changes in plasma prostaglandins, and reduction of blood pressure was moderate (13 mm Hg). It is suggested that vasodilating prostaglandins may contribute to dialysis hypotension. Their origin may not be confined to the kidneys but rather extend to the lungs and circulating blood cells. The in vitro generation of prostaglandins was demonstrated when donor blood was circulated in an extracorporeal dialysis system.

Dinoprost

Effect of repeated plasma exchange on steady state kinetics of digoxin and digitoxin.

The effect of repeated plasma exchanges on the steady state kinetics of digoxin (3 patients) and digitoxin (4 patients) was investigated in 7 patients. Plasma exchange was performed 3 times a week for 4 weeks up to 12 exchanges using a hollow fiber membrane. In each exchange, 4000 ml plasma were filtered within 1 to 2 h and replaced by an albumin containing (20 g/l) physiological electrolyte solution. Digoxin and digitoxin concentrations in blood and filtered plasma were measured by radioimmunoassay. The effects due to the amount eliminated by plasma exchange were distinguished from the effects due to hypoalbuminemia. The eliminative effect was confined to the plasma compartment. It resulted in a marginal decrease in the elimination half-life from 1.6 to 1.59 days for digoxin and 4.3 to 4.2 days for digitoxin. Theoretically, it can be calculated that the hypoalbuminemia caused an increase in the volume of distribution from 451 to 497 l (digoxin) and 35 to 50 l (digitoxin) and a further decrease in the elimination half-life from 4.2 to 4.1 days in the case of digitoxin (not digoxin). If given within 2 h prior to plasma exchange, 13 to 50% of the digitoxin dose (not digoxin) was eliminated. Alteration of digoxin and digitoxin dosage during repeated plasma exchanges is not recommended, but drugs should be given after, not before plasma exchange.

Adult