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P Ott

Publications and source records attributed to P Ott.

At least 91 records · Page 5Linked to original sources
PubMed1994

Hepatic removal of two fractions of indocyanine green after bolus injection in anesthetized pigs.

In the anesthetized pig, we studied the kinetics after intravenous bolus injection of two fractions of indocyanine green (ICG): the genuine ICGg (95-99% of total) and a degradation product, ICGdp (1-5%). Plasma concentrations were followed in the carotid artery and a hepatic vein. ICGg disappearance curves (n = 7) were biexponential with rate constants alpha = 0.189 +/- 0.021 min-1 and beta = 0.0356 +/- 0.0061 min-1. The hepatic extraction fraction was constant with time. A detailed mathematical analysis showed this to be in disagreement with the conventional assumption that the biexponential plasma disappearance curve is a result of backflux from the liver storage to plasma. In contrast, our observations were predicted by an alternative model assuming temporary extrahepatic, extravasal redistribution during first-order, one-way hepatic uptake. Nevertheless, when a large bolus of sulfobromophthalein (BSP) was injected 20 min after ICG, a net backflux of ICG could be demonstrated, presumably due to countertransport. Thus a sufficient description of ICGg kinetics must include the complex kinetic behavior of the hepatic membrane carrier involved. Mass spectrometry suggested that ICGdp is formed by two ICGg molecules. Plasma elimination of ICGdp was slower (alpha = 0.0094 +/- 0.0007 min-1). Analysis of the bile after bolus injection (n = 2) of ICGdp revealed two possible metabolites of ICGdp that were not found in urine. Since BSP injection did not alter the ICGdp disappearance curve, ICGdp is probably not taken up by the same hepatic membrane carrier as ICGg.

Animals↗
PubMed1993

Membrane phospholipid asymmetry in DMPC-induced human red cell vesicles.

Vesicles that do not contain spectrin were released from human erythrocytes by incubation with dimyristoylphosphatidylcholine. The transbilayer orientation of membrane phospholipids was subsequently determined by two independent methods. Incubation with phospholipase A2 revealed that the phospholipid asymmetry observed in red blood cells was essentially preserved in vesicles. By use of the prothrombinase assay a still highly asymmetric distribution of phosphatidylserine could be demonstrated in spite of its slightly increased exposure on the vesicle surface. These results show that membrane phospholipid asymmetry can be maintained in a system that does not contain an intact membrane skeleton or spectrin.

Bee Venoms↗
PubMed1993

ATP-dependent aminophospholipid translocation in erythrocyte vesicles: stoichiometry of transport.

Vesicles released from human red blood cells by incubation with a suspension of sonicated dimyristoylphosphatidylcholine were purified by gel filtration. Purified vesicles and intact red cells had a very similar composition with respect to phospholipids and integral membrane proteins, but spectrin, the major component of the membrane skeleton, was not found in vesicles. Comparison of red cell and vesicle ATP levels (expressed as micromolar ATP per millimolar hemoglobin) showed a marked difference with a reduced content of only about 30% in vesicles, whatever the initial concentration in the erythrocytes. Spin-labeled aminophospholipids (phosphatidylserine and phosphatidylethanolamine) were translocated to the inner vesicle membrane layer at a comparable rate as in intact red cells provided that vesicles contained enough ATP. The maximum fraction of spin-labeled phospholipids translocated to the inner membrane layer was 84% for phosphatidylserine, 65% for phosphatidylethanolamine, 20-40% for phosphatidylcholine, and below 20% for sphingomyelin. The apparent Km of translocation, expressed as percent of total membrane phospholipid, was 0.14% for spin-labeled phosphatidylserine and 1.19% for spin-labeled phosphatidylethanolamine. This compares well to values established earlier for intact red blood cells. The fact that no ATP was synthesized in vesicles allowed determination of ATP consumption by aminophospholipid transport. The basic ATP hydrolysis rate was increased upon the addition of labeled aminophospholipids but not of labeled phosphatidylcholine or sphingomyelin. The stoichiometry between lipid translocation and ATP consumption, calculated from the respective initial velocities, was 1.13 +/- 0.2 for phosphatidylserine and 1.11 +/- 0.16 for phosphatidylethanolamine.

Adenosine Triphosphate↗
PubMed1993

Enhancement of unbound clearance of ICG by plasma proteins, demonstrated in human subjects and interpreted without assumption of facilitating structures.

The kinetics of hepatic removal of protein-bound substances were studied in nine human subjects with various liver diseases by the use of indocyanine green as a model substance. Intrinsic hepatic clearance of indocyanine green was measured by means of a constant infusion of indocyanine green and concentration measurements of indocyanine green in arterial and hepatic venous plasma samples. During the indocyanine green infusion, 1-1.51 of dextran-70 was given whereby a stable dilution of the plasma protein concentration by a factor of 0.6-0.8 was obtained. In each of the subjects, the intrinsic clearance of indocyanine green increased after the protein dilution (range 11-64%). Elimination of ethanol (not protein bound), similarly assessed, was not significantly changed. The traditional hypothesis that unbound clearance (intrinsic clearance divided by the free fraction of the ligand) is independent of protein concentration was refuted since in each of the subjects the protein dilution was followed by a reduction of the unbound clearance of ICG (P < 0.005, n = 9). We examined whether these observations imply some special mechanism (e.g. a hepatocyte protein receptor) by which the unbound clearance is enhanced by the binding protein(s). The previously developed pseudofacilitation model--describing the effects of ligand-protein diffusion and dissociation in an unstirred plasma layer near the hepatocyte--was extended to the case of a mixture of binding proteins, and parameter-free bounds were derived to predict the response of intrinsic clearance to protein dilution. The observed changes of the intrinsic clearance values did not violate these bounds (P < 0.002, n = 9). Thus no facilitating mechanisms are necessary to account for the observed deviations from the traditional hypothesis.

Adult↗
PubMed1993

Plasma elimination of indocyanine green in the intact pig after bolus injection and during constant infusion: comparison of spectrophotometry and high-pressure liquid chromatography for concentration analysis.

Indocyanine green is used to estimate liver blood flow rate and hepatic intrinsic clearance. However, its use as a test substance for studies of liver function has been limited by two puzzling kinetic observations: a biexponential plasma decay after bolus injection with an extremely slow late phase and an apparently steadily decreasing clearance value during constant infusion. These observations have been made with spectrophotometric concentration analysis. In anesthetized 30- to 40-kg pigs, we examined plasma concentration curves of indocyanine green after intravenous bolus injection and during long-term infusion. We compared spectrophotometry with high-pressure liquid chromatography for measurement of plasma indocyanine green concentration. In freshly prepared commercially available indocyanine green, high-pressure liquid chromatography could separately measure two fractions, the genuine indocyanine green (97% to 99% of total) and an in vitro degradation product (1% to 3%). Because their spectra were nearly identical, these fractions could not be distinguished by spectrophotometry. After intravenous administration both fractions were identified in the plasma by high-pressure liquid chromatography. In the first series (n = 6) 25 mg of indocyanine green was injected intravenously for 5 min. When analyzed by high-pressure liquid chromatography, the genuine indocyanine green plasma concentration decay was biexponential with rate constants 0.196 +/- 0.021 (mean +/- S.E.M., n = 6) and 0.0372 +/- 0.0064 min-1. The degradation product of indocyanine green decayed almost monoexponentially, with a rate constant of 0.0093 +/- 0.0002 min-1. With spectrophotometry a biexponential decay was observed with rate constants 0.130 +/- 0.012 and 0.0095 +/- 0.0001 min-1. The biexponential decay of indocyanine green after spectrophotometry was the result of codetermination of the two fractions: genuine indocyanine green was responsible for initial phase, and the degradation product of indocyanine green was responsible for the late phase. In the second series (n = 9), indocyanine green was administered as a constant intravenous infusion. From 90 to 240 min the intrinsic hepatic clearance of genuine indocyanine green did not change detectably with time. In contrast, the degradation product of indocyanine green never reached steady-state concentrations. Because of code-termination of these two indocyanine green fractions, the apparent intrinsic hepatic clearance of indocyanine green estimated from spectrophotometry was steadily decreasing by 8.9% +/- 1% per hour of its initial value. At the same time estimation of liver plasma flow rate based on Fick's principle was not affected by the choice of analytical methodology. These observations indicate that high-pressure liquid chromatography is superior to spectrophotometry for kinetic analysis of indocyanine green elimination.

Animals↗
PubMed1992

Superiority of a vertical sternal lead for detection of arrhythmias during ambulatory electrocardiographic monitoring.

In a preliminary study comparing 7 sets of bipolar leads with standard modified V1 and V5 leads, a vertical sternal lead system with the negative lead just below the suprasternal notch, and the positive lead over the xiphoid had the greatest P-wave area. In the current study, the vertical sternal and modified V1 leads were obtained simultaneously using 2-channel ambulatory electrocardiographic recorders in 50 consecutive patients undergoing diagnostic ambulatory electrocardiography for suspected arrhythmias. The vertical sternal lead provided tracings with a larger P-wave area compared with that of the modified V1 (0.58 +/- 0.44 vs 1.23 +/- 0.69 mm2; p less than 0.0001), and a greater QRS complex (9.23 +/- 4.16 vs 11.78 +/- 4.90 mm; p = 0.006). During premature atrial contractions and supraventricular tachycardia, P-wave visibility was significantly better in the sternal lead than in V1 (p less than 0.001). Furthermore, sternal lead tracings were superior with regard to overall quality and noise level. It is suggested that the vertical sternal lead replace the currently used modified V1 during ambulatory electrocardiographic monitoring. This lead system in conjunction with the standard modified V5 lead should be useful in the differential diagnosis of atrial arrhythmias.

Adolescent↗
PubMed1992

Ultrastructural localization of hyaluronan in myelin sheaths of the rat central and rat and human peripheral nervous systems using hyaluronan-binding protein-gold and link protein-gold.

Neural tissue of central (rat spinal cord) and peripheral origin (rat sciatic nerve, nerve fascicles of rat skin and iris and of human conjunctiva) was processed by osmium tetroxide/microwave fixation and embedded in epoxy resin. Hyaluronan-binding proteins and link proteins coupled to 15-20-nm gold particles were used as markers in a one-step post-embedding procedure for identifying hyaluronan (hyaluronic acid) at the ultrastructural level. All myelin sheaths in both rat and human material were found to be intensely labelled. The specificity of the hyaluronan-binding probes was demonstrated by the total loss of labelling following treatment of sections with hyaluronidase or by preincubating either the probes with hyaluronan oligosaccharides or the sections with unlabelled hyaluronan-binding protein. The identified hyaluronan appears to be located extracellularly, but is precise role here remains to be elucidated.

Animals↗
PubMed1992

Intrinsic hepatic clearance of indocyanine green in the pig: dependence on plasma protein concentration.

Intrinsic hepatic clearance (K) of indocyanine green (ICG) is used as a quantitative measure of liver function. ICG is tightly bound to plasma proteins. The purpose of this study was to examine the effect of changes of plasma protein concentration on K in anaesthetized pigs with intact hepatic circulation. In addition, an attempt was made to evaluate the corresponding changes of the unbound intrinsic clearance of ICG. The plasma protein concentration was changed by exchange of plasma with either dextran-70 or donor pig plasma. Plasma albumin concentration was measured in a peripheral artery and changes of the concentrations of other plasma proteins were assumed to parallel those of albumin. ICG was given as a constant infusion and K was calculated from peripheral artery and hepatic vein concentrations of ICG according to the sinusoidal perfusion model. One experimental series comprised 3 measurement periods: From Period 1 to Period 2 (eight animals) albumin concentration was decreased by 36.6 +/- 6.5% (Mean +/- SD). This was associated with an increase of K of 32.8 +/- 28.8% (P = 0.004). From Period 2 to 3 (five animals) albumin was increased by 13.2 +/- 3.2% and K decreased by 18.5 +/- 8.3% (P = 0.03). In the second experimental series (eight animals), albumin concentration was increased by 21.6 +/- 10.3% and K decreased by 20.3 +/- 8.1% (P = 0.001). For both series, changes in albumin concentration were associated with oppositely directed changes of K in 20 out of 21 comparisons (P less than 0.001). Thus K depends not only on hepatocyte function but also on plasma protein concentration. This finding should affect interpretation of K when used as a liver function test. Changes of the unbound intrinsic clearance of ICG were examined indirectly by means of the K.a product (a: albumin concentration). According to the overall evaluation of the data the unbound intrinsic clearance of ICG was not affected by the changes in plasma protein concentration, but the results were internally inconsistent, apparently due to a time-dependency of the K.a product. We suggest this to be due to a slow but steady decrease of the 'background' K. After correction for the average decrease of K of 0.102% per min our data were in accordance with the hypothesis that the unbound clearance of K was enhanced by the binding protein(s) of ICG.

Animals↗
PubMed1992

Evaluation of electrocardiographic leads for detection of atrial activity (P wave) in ambulatory ECG monitoring: a pilot study.

The usual lead systems for ambulatory ECG monitoring (AECG) used in the evaluation of arrhythmias is a modified bipolar V-1 and V-5. A comparison of various lead systems to enhance the detection of atrial activity (p waves) has not been reported. We evaluated various surface lead systems in 12 subjects comparing p waves recorded at 20 mm/mV and 50 mm/sec. We compared p wave area, amplitude, and duration from modified bipolar V1 and V5 as well as seven nonstandard leads recorded on a AECG monitor. Of the seven nonstandard leads, a vertical sternal lead, with the negative pole just below the suprasternal notch and the positive pole at the xiphoid process, had the largest area (1.46 +/- 0.65 mm2), and also had a greater area than the standard V1 (0.88 +/- 0.45 mm) and V5 (1.06 +/- 0.49 mm2) lead system (P less than 0.01). We conclude that the bipolar vertical sternal lead system provides a larger p wave area than seven nonstandard bipolar lead systems and the two standard lead systems currently used in AECG monitoring. Replacement of the modified bipolar V1 lead with a vertical sternal lead should improve the recognition of atrial activity and, therefore, enhance the diagnosis of cardiac arrhythmias.

Adult↗
PubMed1992

Small infarctions of cochlear, retinal, and encephalic tissue in young women.

BACKGROUND AND PURPOSE: Recently, a rare syndrome that involves uniformly the brain, inner ear, and retina in previously healthy young women has been described. Brain biopsies and ophthalmologic examinations disclosed small infarcts as a pathoanatomical substrate of the disease. In previous reports, an autoimmune disorder or a coagulopathy have been suggested as possible etiologies. CASE DESCRIPTIONS: Both patients (aged 22 and 20 years) had brain involvement with neurological and neuropsychological deficits. Multifocal small hyperintensities were shown in magnetic resonance imaging of the brain. Findings of cerebrospinal fluid examination and electroencephalography were pathological in case 1 and of cerebral angiography in case 2. Both patients had a neurosensory hearing loss and multiple retinal branch arteriolar occlusions. Both women were on fenfluramine before onset of the disease. In case 1, attacks recurred during a follow-up of 34 months. At onset of the disease the 5-hydroxyindoleacetic acid and homovanillic acid levels of the cerebrospinal fluid were reduced; 13 months later the 5-hydroxyindoleacetic acid level was still reduced and the homovanillic acid level was low-normal. In case 2, with the longest follow-up of 13 years, the disease was active during only the initial 2 1/4 years. During this period a combination of oral anticoagulant and antiplatelet agents was ineffective. CONCLUSIONS: Our findings could not support current etiologic hypotheses. Whether changes in 5-hydroxyindoleacetic acid and homovanillic acid levels in the cerebrospinal fluid and/or fenfluramine intake play a role in the pathogenesis of the disease remains to be elucidated.

Adult↗
PubMed1991

[Optimizing warfarin treatment].

For monitoring of warfarin treatment only analyses with documented International Sensitivity Index should be used. Until further studies clarify the matter, we recommend the therapeutic intervals proposed by the American College of Chest Physicians and the National Heart, Lung, and Blood Institute. For induction of treatment, a daily warfarin dose of 10 mg is useful. Overlapping heparin therapy is recommended for at least five days. Day-to-day variation of dietary vitamin K intake of less than 250-500 micrograms and an alcohol consumption below 47 g/day will not disturb anticoagulation. Bleeding is more common during long-term treatment, among elderly patients and in patients with cerebral arteriosclerotic disease, especially in combination with uncontrolled hypertension. Bleeding patients often have underlying pathology which should be looked for.

Drug Interactions↗
PubMed1991

Congenital haemolytic anaemia in a low birth weight infant due to congenital stomatocytosis.

A baby girl born at 31 weeks gestation showed severe haemolytic anaemia and hyperbilirubinaemia which led to exchange transfusion within the first 12 hours of life. There was no blood group incompatibility between mother and child but there was a marked stomatocytosis of the baby's red blood cells. Family history revealed a congenital stomatocytosis in the mother. Biochemical characterization of the defect was performed. Phospholipid analysis of the erythrocyte membrane of mother and child showed an increase in phosphatidylserine with a compensatory decrease in phosphatidylcholine and phosphatidylethanolamine. SDS-electrophoresis showed multiple modifications of the protein pattern with a decrease in band 6, an increased content of band 4.1b, a slight decrease in band 7 and a clear change in the shape of the protein band 3 pattern. The results suggest that the basis of the observed abnormalities is a common defect in protein posttranslational modification, rather than multiple genetic defects in the synthesis of several proteins. Haematologic, biochemical and clinical course of the disease in this preterm infant are discussed.

Anemia, Hemolytic, Congenital↗
PubMed1991

Acute ethanol administration reduces the antidote effect of N-acetylcysteine after acetaminophen overdose in mice.

1. The combined antidote effect of N-acetylcysteine and ethanol on the toxicity of acetaminophen was investigated. 2. Fed male mice were given acetaminophen i.p. (600 mg kg-1) and after 5 min in addition ethanol i.p. (0.2 ml, 19% v/v), N-acetylcysteine i.p. (1.2 g kg-1, 0.2 ml), N-acetylcysteine + ethanol i.p. (same doses as given individually) or saline i.p. (0.4 ml). Survival rates were determined after 24, 48, 72 and 96 h. 3. In the N-acetylcysteine group the survival rate was 85%. This rate was significantly reduced to 43% in the N-acetylcysteine + ethanol group (P = 0.0001). In the groups given ethanol or saline alone only 7% and 3%, respectively, survived 96 h. 4. The data suggest that the protective effect of N-acetylcysteine on acetaminophen-induced toxicity in fed mice is reduced by concomitant administration of ethanol. This may explain the clinical observation that ingestion of ethanol worsens the prognosis after acetaminophen intoxication.

Acetaminophen↗
PubMed1990

[Consumption of, overdose and fatal poisoning with analgesics in Denmark 1979-1986].

During 1978-1987 the annual sale of analgetics increased by 28% to 164 millions defined daily doses (mDDD) per year. Paracetamol changed status to over-the-counter drug by 1.1.1984 as did combinations of acetylicsalicylic acid and codein 14.5.1984. The consumption of paracetamol increased rapidly to 47 mDDD/-year, the mortality steadily decreasing to 0.07 deaths/mDDD in 1986. The consumption of salicylics decreased from 113 to 94 mDDD, of which the salicylic/codein combination constituted an increasing fraction. The mortality of salicylics increased from 0.05 death/mDDD in 1983 to 0.27/mDDD in 1986. Opoids except dextropropoxyphene increased three times during the period, while the risk of fatal poisoning decreased from 10 to 5 deaths/mDDD. Dextropropoxyphene consumption was stable 1978-86 while mortality doubled from 59 to 121 per year. After a National Board of Health initiative, 66 dextropropoxyphene deaths were seen in 1987. Paracetamol mortality was 10 times lower than in England and Wales, where a dextropropoxyphene/paracetamole combination (not available in Denmark) was often involved. From a toxicological point of view over the counter status for combinations of strong and weak analgetics are not desirable.

Analgesics↗