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Biomedical subjects

P Ott

Publications and source records attributed to P Ott.

At least 19 recordsLinked to original sources

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

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

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

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

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

[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

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

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

[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

Consumption, overdose and death from analgesics during a period of over-the-counter availability of paracetamol in Denmark.

During the period 1978-1986, annual sales of paracetamol in Denmark increased from 1 million defined daily doses (DDD) (3 g) to 47 million DDD, while the number of admissions and deaths from overdose increased from 26 to 202 and from 1 to 3-4, respectively. The corresponding figures for salicylates are a decrease in sales from 113 to 94 million DDD, an increase in admissions from 282 to 595, and an increase in deaths from 5 to 22. From 1 January 1984 paracetamol became available on an over-the-counter basis. The figures for 1983 and 1984 were an increase in sales from 14 to 28 million DDD, an increase in admissions from 114 to 198, and an increase in deaths from 0 to 4. The number of deaths from opioid overdose remained constant at a value of about fifty during this period, the mortality per dose being about 20-fold higher than for paracetamol and salicylates. Dextropropoxyphene-related deaths increased twofold to 121 in 1986, with unchanged sales figures. A campaign launched by the National Board of Health resulted in a reduction in the number of deaths from dextropropoxyphene to 66 in 1987. The main effect of over-the-counter release of paracetamol was a dramatic increase in sales, without the epidemic of deaths observed a decade ago in the UK. It is suggested that the higher mortality of paracetamol poisonings in the UK compared to Denmark is related to the dextropropoxyphene content of the combination product, which is not available in Denmark. From an epidemiological toxicological viewpoint such combinations are not justified.

Acetaminophen

The influence of extracorporeal circulation on erythrocytes and flow properties of blood.

The influence of extracorporeal circulation on red blood cells and flow properties of blood was studied in 10 patients undergoing aorta-coronary bypass grafting. Blood samples were drawn on admission, under general anesthesia before the operation, during extracorporeal circulation, immediately after extracorporeal circulation, and 24 hours after extracorporeal circulation. Echinocytes were found during and shortly after extracorporeal circulation, but disappeared within 24 hours. Washing the cells in buffer restored the normal discocytic shape, which indicated that a plasma factor was responsible. Red cell membrane lipids were not affected. Analysis of the membrane proteins revealed a decrease of ankyrin after extracorporeal circulation, which was prevented by protease inhibitors during preparation. This suggests an increased proteolytic activity of the plasma after extracorporeal circulation. Red cell deformability was not altered. Plasma viscosity and hematocrit were markedly reduced by hemodilution with the priming solution. Their low levels resulted in a low blood viscosity during extracorporeal circulation, which was even lower at 26 degrees C than before or after the operation at 37 degrees C. We conclude that the red cell is affected by extracorporeal circulation. The flow properties of blood, however, are not impaired, but are improved by hemodilution.

Aged

Predicting failure of low-dose prophylactic heparin in general surgical procedures.

Despite prophylaxis with low-dose heparin (LDH), postoperative thromboembolism (TE) still occurs in 10 per cent of patients undergoing abdominal operations. To identify predictors of TE in spite of LDH, 171 patients undergoing abdominal operations and receiving LDH were screened with the fibrinogen uptake test. Diagnosis of TE was confirmed in 24 (14 per cent; 95 per cent confidence limits of 9 to 20 per cent) by either venography or pulmonary scintigraphy, or both, or autopsy. As analyzed by multiple logistic regression, only age, body mass index, preoperative hemoglobin concentration and colorectal operations (yes or no) contributed to the prediction of failure of LDH, whereas sex, malignant lesion, previous TE, hypertension, diabetes mellitus and varicose veins did not. Based on the first 81 patients, an index was constructed that was able to identify 11 of 13 patients with TE and exclude 34 of 68 without TE. This index was then applied on a second series of 90 patients in whom it correctly identified ten of 11 patients with TE and excluded 40 of 79 patients without TE. It is concluded that, with the use of the index, it is possible to identify a group of patients undergoing elective abdominal operations in whom LDH is not sufficient prophylaxis. A practical approach to bedside prediction of failure of LDH prophylaxis by use of a simple score table is suggested.

Abdomen

A simple technique for predicting maintenance dosage of warfarin--is it better than empirical dosing?

In a prospective, randomised trial the clinical utility of a predictive warfarin maintenance dosing technique was compared with the more commonly employed empirical dosing method. A preliminary study in 35 patients established the applied technique for predicting the maintenance dosage of warfarin from the prothrombin activity on Day 4 of initial standardised warfarin administration. Forty-three patients admitted with venous thrombotic disease were investigated. All received the same loading dose of warfarin (10 mg daily) until the prothrombin percentage activity (Normotest) was less than 25%. Significantly more patients were correctly stabilised when warfarin doses were based on prediction than when they were empirically adjusted (86% vs 50%). Also, the median number of days to achieve stable anticoagulation was lower (8 vs 11 days). It is concluded that this simple predictive technique to determine the maintenance dosage of warfarin is superior to empirical dosing.

Adolescent

Haemolytic anaemia in analpha-lipoproteinaemia (Tangier disease): morphological, biochemical, and biophysical properties of the red blood cell.

A patient with familial analpha-lipoproteinaemia (Tangier disease) was found to have stomatocytosis and haemolytic anaemia. The analysis of the red cell membrane constituents revealed a low cholesterol content (90 nmol/ml red cells, control 130 nmol/ml red cells), a decreased cholesterol/phospholipid ratio (0.54, control 0.78), high phosphatidylcholine (41.5%, control 30.6%) and low sphingomyelin (18.8%, control 27.6%). The electrophoretic membrane protein pattern was normal. Osmotic gradient ektacytometry and osmotic resistance showed a decreased surface/volume ratio, which caused an increased filtration resistance in 3 microns pores. The elasticity of the membrane was unchanged. Functional membrane properties were altered: the anion exchange rate was increased, whereas alkali cation fluxes were normal. The capacity to release vesicles was reduced. This case represented a new type of stomatocytosis. It contributes to the understanding of the role of cholesterol and phospholipids in the red cell membrane and biomembranes in general.

Anemia, Hemolytic, Congenital

Erythrocyte phospholipid organization and vesiculation in hereditary high red cell membrane phosphatidylcholine hemolytic anemia.

We have studied the erythrocyte membrane phospholipid organization in hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA) and the response of these red cells during incubation with sonicated suspensions of dimyristoylphosphatidylcholine (DMPC). Although both the absolute and relative amounts of phosphatidylcholine were elevated in these red cells, the relative distribution of phosphatidylcholine on both sides of the membrane bilayer and the transbilayer mobility of phosphatidylcholine were normal. HPCHA erythrocytes showed elevated absolute amounts per cell of both protein and lipid and an increased cellular ratio of protein to phospholipid. Incubation of normal red cells with DMPC led to the formation of echinocytes, followed by the release of acetylcholinesterase-containing vesicles. Both echinocyte formation and vesiculation were markedly reduced in red cells from patients with HPCHA. Studies with red cells from patients with liver disease, cells that also have elevated relative amounts of membrane phosphatidylcholine and increased amounts of lipid per cell, revealed normal echinocyte formation and normal DMPC-induced vesiculation. We conclude that the altered lipid composition of HPCHA erythrocytes per se is not responsible for the observed reduction in DMPC-induced vesiculation, but that it is more likely the result of a modification in the protein moiety of these cells. This putative protein abnormality could enhance binding of phosphatidylcholine to red cell membranes and could explain the elevated phosphatidylcholine content of HPCHA erythrocytes and their inability to vesiculate.

Anemia, Hemolytic, Congenital