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Biomedical subjects

F Keller

Publications and source records attributed to F Keller.

At least 253 records · Page 14Linked to original sources

Multicenter evaluation of a chromogenic substrate method for photometric determination of prothrombin time.

A multicenter study of a chromogenic substrate method for photometric determination of prothrombin time was conducted in order to evaluate its clinical application. Seven laboratories participated in the study using a total of 742 plasma samples from 417 patients on oral anticoagulant therapy, 261 healthy subjects and 64 patients with different diseases especially of the liver as well as 30 patients with hereditary deficiency of coagulation factors II, V, VII, X. The chromogenic PT method was compared to a standardized coagulometric PT assay which uses the same sensitive human placenta thromboplastin calibrated against international reference preparations. A high correlation of the prothrombin ratio values of the chromogenic and the coagulometric assay was obtained in 402 plasma samples (r = 0.940; y = 1.02x - 0.1). The study showed that the chromogenic PT reagent is sensitive to deficiency of the coagulation factors of the extrinsic pathway but not affected by heparin up to 1 IU/ml because of the heparin antagonist added. The precision (coefficient of variation) of the photometric method ranged between 0.6 and 3% (intraassay CV) and between 1.4 and 5.8 (interassay CV). The International Sensitivity Index (ISI) obtained for the used lot was 1.09. The therapeutical range in percentage activity for patients in a stable phase of an anticoagulant therapy was found to be from 15 to 27 percent of normal. The results of the clinical evaluation proved the good comparability of the new chromogenic PT test with coagulometric methods, its high factor sensitivity, good reproducibility and easy performance.

Anticoagulants↗

Choline and acetylcholine metabolism in slice cultures of the newborn rat septum.

The incorporation of [3H]choline into acetylcholine and other choline-containing compounds was investigated in slice cultures of the septal area of newborn rats. At choline concentrations in the range of the high affinity transport mechanism (0.1-1 microM) most of the labeled choline was incorporated into phosphorylcholine, followed by lipids, acetylcholine and the free choline pool. Hemicholinium-3 (1-10 microM) lead to a marked decrease of acetylcholine synthesis, whereas choline accumulation or phosphorylcholine synthesis were not decreased. Both basal and K+-induced release of acetylcholine were Ca2+ dependent. The efflux of choline was not stimulated by high K+. When choline was absent from the incubation medium, the slices were able to liberate significant amounts of the [3H]choline previously incorporated into phospholipids, and were also able to synthesize some acetylcholine. In choline-free medium, acetylcholine synthesis was greatly enhanced by depolarization. During the period in culture, there was a decrease of the incorporation rate of [3H]choline into phosphorylcholine and an increase of the incorporation rate into acetylcholine. The tissue structure was well preserved after several weeks in culture. After staining for acetylcholinesterase, the cholinergic neurons in the cultures showed a similar morphology to that seen in situ. The main conclusions of the present study are: cholinergic neurons in slice cultures develop and behave in a manner which is very similar to their in situ counterparts; the main divergence from previous studies of choline metabolism in tissue culture is the substantial incorporation rate of choline into acetylcholine at choline concentrations in the range of the high affinity uptake mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Selective kainic acid lesions in cultured explants of rat hippocampus.

The influence of the excitotoxin kainic acid (KA) on cultivated explants of rat hippocampus was investigated. Addition of 3 microM KA to the culture medium over 24-48 h induced a destruction of the pyramidal cells in the CA3 region, whereas the CA1 pyramidal cells and the granule cells were left undamaged. Higher concentrations (10-100 microM) of KA destroyed also the latter cell groups. The selectivity of the KA lesion at 3 microM was further indicated by the fact that the acetylcholinesterase-positive neurons in the hippocampus were not destroyed through KA administration and that the stereoisomer dihydrokainic acid was ineffective in inducing lesions. Application of tetrodotoxin did not protect the CA3 pyramidal cells from KA lesion, whereas gamma-glutamylaminomethylsulphonic acid (GAMS) only offered a very small, statistically not significant, protection. Baclofen protected the cultures slightly from KA lesions but not when added together with GAMS. Possible mechanisms responsible for the KA lesions in these cultures are discussed.

Acetylcholinesterase↗

Efficacy of sucralfate in the prevention of recurrence of duodenal ulcers.

Eighty-four patients who were endoscopically confirmed to have healed duodenal ulcers were entered into this 1-year, double-blind, placebo-controlled trial of sucralfate, 1g twice daily, in the prevention of duodenal ulcer recurrence. Patients remained in the study until recurrence of ulceration was endoscopically confirmed. Sixty-one patients could be evaluated for efficacy of treatment. Within 6 months, 23 of 31 placebo patients (74%) and 6 of 30 sucralfate patients (20%) had ulcer recurrence. At 12 months, 25 of 31 placebo patients (80%) and 8 of 30 receiving sucralfate (27%) had ulcer recurrence. The lower rate of ulcer recurrence in patients receiving sucralfate was significant (p = 0.0001). Survival curves also showed that sucralfate was significantly more effective in preventing relapse (p = 0.0001). Three patients were judged as experiencing drug-related side effects, two of which were in the placebo group. The results indicate that sucralfate is significantly more effective than placebo in the prevention of recurrence of duodenal ulcer disease.

Clinical Trials as Topic↗

Therapeutic aminoglycoside monitoring in renal failure patients.

In patients with normal renal function, defined peak (5-10 mg/L) and trough levels (less than 2 mg/L) for gentamicin, tobramicin, and netilmicin are considered therapeutic. Netilmicin peak and trough levels were investigated in 50 patients requiring hemodialysis due to acute (70%) or permanent (30%) renal failure. Netilmicin was given at a dosage interval of 24 h, with a loading dose on the first day (1.5 mg/kg) and a reduced daily maintenance dose (0.5 mg/kg) supplemented to the posthemodialysis dosage (1.3 mg/kg) after each hemodialysis. As compared with studies on patients not requiring hemodialysis, mortality (44%) was higher, mainly due to uncontrolled infection, whereas ototoxicity (17%) was not. Peak (5.9 +/- 1.7 mg/L) and trough plasma levels (3.0 +/- 0.9 mg/L) were significantly lower in patients who did not respond and died than were peak (8.2 +/- 2.5 mg/L) and trough (3.8 +/- 1.2 mg/L) levels in patients responding to aminoglycoside treatment. In renal failure patients, there is obviously not only the risk of overdosing and toxic side effects but also the risk of insufficient bactericidal effect as a result of underdosing. Consequently, by use of an aminoglycoside dosage similar to the present schedule, peak levels (5-10 mg/L) as desired in normal subjects but trough levels (2.5-5 mg/L) that are considerably higher than in normal subjects should be the target concentrations for patients with advanced renal failure.

Acute Kidney Injury↗

Delusional depression and suicide.

After a short survey of the relevant literature, the authors discuss the significance of delusional depression symptoms for suicidality, whereby they do not regard such symptoms alone as a sufficient condition for classifying a delusional patient as suicidal. In a comparison of delusional depressed patients with a non-delusional control group (matched pairs), the former were adjudged to be significantly less suicidal than the control group and did not differ from the control group in regard to suicide frequency.

Delusions↗

[Initial experiences with pro-urokinase in acute myocardial infarct].

Pro-urokinase is a fibrin-specific, single-chain, high molecular form of urokinase that induces thrombolysis without fibrinogenolysis in experimental animals. Consequently, the potential advantage of pro-urokinase is that its activation can be limited to the site of a clot. Its efficiency was assessed in ten patients with acute transmural myocardial infarction. Reperfusion occurred in only two patients. In five out of seven patients with persistent complete coronary occlusion, clot lysis could be achieved by intracoronary streptokinase application within 30 min after completion of the pro-urokinase infusion. Fibrinogen and alpha 2-antiplasmin changed only moderately during pro-urokinase infusion. These preliminary data may indicate a limited thrombolytic efficiency of pro-urokinase in patients with acute myocardial infarction.

Adult↗

[Elimination of drugs by hemofiltration. Principles and literature data].

The elimination of substances during hemofiltration depends on the special properties of the used wide-porous membranes. High filtration-fractions are achieved and, in practice, all substances with a molecular weight below 10,000 Dalton pass the membrane. Also drugs are filtrated equivalent to their unbound free plasma-fraction. A quantitative elimination of drugs during hemofiltration is to expect, 1. if a sufficient ultrafiltration rate of 10 ml/min or more is reached, which is the upper limit of spontaneous CAVH, 2. if the sieving-coefficient or plasma-protein-binding enables a sufficient passage and 3. if the serum concentration of the drug related to its administered dose is high, i.e. the volume of distribution is small. An adjustment of drugs is partially necessary during hemofiltration. A simple way is to calculate the total creatinine-clearance to derive dosage modifications.

Hemofiltration↗

Aluminium load in patients with analgesic nephropathy.

It is well-known that plasma aluminium in haemodialysis patients increases with the amount of aluminium hydroxide consumption. In a cross-sectional study at our haemodialysis centre we found that mean plasma aluminium levels are significantly higher in haemodialysis patients with analgesic-associated nephropathy (AAN) than in haemodialysis patients with other kidney diseases (controls) (logarithmic mean +/- SD = 1.93 +/- antilog 0.32 versus 1.21 +/- antilog 0.31 mumol/l; p = 0.001). AAN patients consume a significantly higher amount of aluminium-containing phosphate binders than the controls (21 +/- antilog 0.3 versus 13 +/- antilog 0.4 g/kg body weight/year; p = 0.007). These findings may be explained by the higher incidence of peptic ulcer disease in AAN patients, since hyperacidity decreases the phosphate-binding effect. Analgesic patients also need more aluminium-containing stomach medication than do patients with other kidney diseases (0.21 +/- antilog 1.15 versus 0.03 +/- antilog 0.87 g/kg body weight/year; p = 0.0001). A statistically significant correlation was obtained between bone aluminium and duration of phosphate binder consumption (r = 0.6459; n = 14; p less than 0.05). There was no correlation between plasma aluminium and bone aluminium. Anaemia was more pronounced in the AAN patients than in the others (mean haemoglobin 8.4 +/- 1.9 vs. 9.2 +/- 2.0 g%; p less than 0.02). Dialysis dementia was observed in 4 AAN patients. We conclude that the higher plasma aluminium levels in AAN patients represent a higher aluminium load which may be followed by higher aluminium toxicity.

Aluminum↗

The organization of intrinsic hippocampal connections in explants of rat hippocampus studied by topical application of HRP crystals.

Hippocampal slices were taken from 7-day-old rats and maintained in vitro for 1-3 weeks. The organization of intrahippocampal connections in these explants was studied by placing onto the tissue small crystals of horseradish peroxidase (HRP) soaked with the detergent Nonidet. Antero- and retrograde transport of HRP was visualized by diaminobenzidine. The principal arrangement of intrinsic hippocampal connections closely resembles the in situ situation of the adult rat. The use of HRP crystals provides a fast and convenient tool for the study of connections in brain explants.

Animals↗

Effects of amiloride on Na+ content and pinocytosis in Entamoeba histolytica.

Amiloride, a blocker of Na+ leak and Na+-H+ exchange in animal cells, caused cells of Entamoeba histolytica to release Na+ (up to 40% of their original Na+ content within 90 min, at an amiloride concentration of 3 mM); K+ content was not affected. By comparing the unidirectional uptake of 22Na+ with that of the fluid-phase marker 125I-labeled poly(vinylpyrrolidone) we established that the amiloride-induced Na+ loss was due to inhibition of pinocytic Na+ uptake rather than to blockage of an amiloride-sensitive transport system in the plasma membrane. Amiloride penetrated the cells, and both its intracellular concentration and its effect on pinocytosis increased with pH. The permeant weak base quinacrine similarly inhibited pinocytosis in a pH-dependent manner. We conclude that the effect of amiloride on pinocytosis and, consequently, on Na+ content was due to its properties as a permeant weak base.

Amiloride↗