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Biomedical subjects

H Wisser

Publications and source records attributed to H Wisser.

At least 37 records · Page 2Linked to original sources

Dopamine infusion in healthy subjects and critically ill patients.

1. Little is known about the metabolism and the pharmacokinetics of dopamine (DA) in critically ill patients. To study the influence of the total administered DA dose on the disposition of free (i.e. unconjugated) and sulfoconjugated DA, plasma levels of free and sulfoconjugated DA were measured following infusion of 5 micrograms DA/kg per min for 0.5 and 3 h in six healthy volunteers and in eight critically ill patients receiving DA at the same infusion rate for 6.5 to 329 h. 2. In patients and volunteers steady state concentrations of free DA showing fairly large inter-individual variations (12.4-73.4 micrograms/L) were reached within 10 min of the beginning of the infusion. 3. DA sulfate was generated immediately. In volunteers peak values of the sulfoconjugate were observed 15-60 min after the termination of the DA infusion. In patients steady state concentrations of conjugated DA (63-80 micrograms/L) were reached within 5-10 h of DA infusion. 4. The initial half-life (t1/2 alpha), the terminal elimination half life (t1/2) and the distribution volume of free DA in the volunteers were significantly higher after 3 h of the DA infusion as compared to the shorter infusion. These parameters as well as the total plasma clearance of free DA were independent of the length of the DA infusion period in patients. The large distribution volumes of 19.8-75 L/kg indicate that DA has been taken up by peripheral tissues. 5. Substantial inter-individual variations in the patients' clearance of free DA (3.9-16.5 L/kg per h) may partly explain the variability in haemodynamic responses to DA infusion reported in clinical studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Magnitude and kinetics of alterations in plasma catecholamines and leukocyte beta-adrenergic receptors in response to anaesthesia and surgery.

We studied the response of the sympatho-adrenal system to varying intensities of different stimuli. Concentrations of norepinephrine and epinephrine in plasma as well as densities of beta 2-adrenergic receptors on mononuclear leukocytes were determined in patients subjected to operations of varying complexity and different types of anaesthesia. In patients undergoing hysterectomy (n = 9), the maximal increases in plasma norepinephrine and epinephrine were 2.7- and 2.8-fold, respectively, corresponding to a post-operative decrease of the mononuclear leukocyte beta 2-adrenergic receptors of 27% after 4 hours. Patients with coronary revascularization (n = 17) were randomly selected to receive either enflurane/N2O or neurolept anaesthesia. During intraoperative periods of stress, such as cardiopulmonary bypass and hypothermia, norepinephrine and epinephrine levels were 2-3 times higher in the neurolept patients, compared with the enflurane patients. In the former group, the respective maximal norepinephrine and epinephrine concentrations were 9.7 and 28 times the vasal values of the non-anaesthetized patients. One day postoperatively, the mononuclear leukocyte beta 2-receptor density decreased maximally by 45 +/- 11% in the enflurane patients, and by 53 +/- 6% in the neurolept patients. As early as two to five days after cardiac surgery, beta 2-receptor densities were no longer distinguishable from the preoperative values. Significant correlations between the increases in catecholamine concentrations and the decreases in beta 2-receptor densities did not exist. It is concluded that enflurane blocks the sympatho-adrenal response to surgical stress more effectively than neurolept anaesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Antipsychotic Agents↗

Antibodies as a source of analytical errors.

This review discusses the interference in clinical chemical analysis caused by autoantibodies and by antibodies to foreign antigens. The nature of these disturbances, their occurrence, prevalence, and detection, the different ways in which they are manifested, the clinical consequences of the failure to recognize such interference, and finally methods for avoiding these disturbances are discussed. Interference by cold agglutinins in the automatic determination of the erythrocyte count, interference by cryoglobulins in the determination of the leukocyte count, and EDTA-induced thrombocyte agglutination are well documented as sources of error in the analysis of haematological parameters. Enzyme determinations may be affected by the occurrence of macro-complexes of the measured enzyme with immunoglobulins. This type of interference, for example, may occur in the determination of amylase and creatine kinase. Immunoassays for the determination of hormones or tumour markers are sensitive to autoantibodies and heterophilic antibodies. The former are particularly important in the determination of thyroid hormones, where the interference is method-dependent. In several immunoassays, interference by heterophilic antibodies can be abolished by the addition of non-immune serum. Finally, rheumatoid factors, antibodies administered for therapeutic purposes, and monoclonal gammopathies are possible sources of interference in the determination of various analytes.

Antibodies↗

Alterations of beta-adrenoceptors on human leukocyte subsets induced by dynamic exercise: effect of prednisone.

1. In order to investigate exercise-induced changes of beta 2-adrenoceptors on human leukocyte subsets, beta-adrenoceptor density was determined as specific binding of [125I]-iodocyanopindolol to granulocytes, monocytes, B and T lymphocytes of six subjects immediately before and after exercise and after 30 min of rest. 2. A 10 min graded bicycle exercise with a workload of 50-250 W caused a transient increase of granulocytes, monocytes, B and T cells of about 32, 43, 120 and 25%, respectively. 3. While the number of beta 2-adrenoceptors in granulocytes remained unchanged, beta-adrenoceptor densities in B cells, T cells and monocytes increased from pre-exercise mean values of 2730, 870 and 2400 binding sites/cell to 3500, 1230 and 3220 binding sites/cell, respectively, under physical stress. The rise in receptor numbers was accompanied by an enhanced isoprenaline-stimulated cyclic AMP formation in unfractionated mononuclear leukocytes (MNL) of about 26% as well as by a 2-3-fold increase in plasma catecholamine levels. Cell concentrations, beta 2-adrenoceptor numbers and adrenergic responsiveness returned to normal after 30 min rest. 4. Administration of 60 mg prednisone 2 h before exercise resulted in granulocytosis and lymphopenia with a preponderant effect on the exercise-induced rise in B cells and monocytes. Corticosteroids showed no effect on stress-induced changes of beta 2-adrenoceptors and responsiveness. 5. It is concluded that exercise-induced increases in beta 2-adrenoceptor density and adrenergic responsiveness of unfractionated MNL are caused by a release of receptor-enriched cells into the circulation, particularly of B lymphocytes and monocytes which carry the highest beta 2-adrenoceptor density.

Adult↗

Quantitative monitoring by high-performance liquid chromatography of the dissociation of human serum cholinesterase by limited proteolysis.

Proteolytic action on human serum cholinesterase, a tetrameric enzyme, results in a partial disintegration which can be recorded only qualitatively by time-consuming electrophoretic techniques. In this study, a rapid high-performance liquid chromatographic method was used for the separation and determination of the active dissociation products. Separation of the cholinesterase subunits was accomplished by high-performance gel permeation chromatography on a combination of DIOL columns (Zorbax GF 450/GF 250) in 0.2 M phosphate buffer (pH 7.0). Detection and quantification of enzyme activity in the fractionated eluate were carried out using a Flexigem analyser (substrate, butyrylthiocholine). On limited tryptic digestion of partially purified human ChE, up to three peaks of enzyme activity could be identified. Their elution volumes corresponded to apparent molecular masses of 480,000, 270,000 and 120,000, indicating, in addition to the tetrameric holoenzyme, a dimeric and a monomeric form. Quantification of the relative amounts of individual enzyme activity peaks revealed that in the course of degradation, the dimer appeared first, followed by the monomer. This suggests that the first step in the sequence of dissociation is cleavage of the tetramer into a pair of dimers, then further into the monomeric subunit. During the incubation with trypsin, a significant change in the pattern of the different peaks had already occurred when the total enzyme activity was only slightly reduced.

Cholinesterases↗

[Adverse reactions and changes in norepinephrine and epinephrine in the plasma after intravenous thyroliberin in persons with normal and abnormal thyroid function].

14 normal volunteers, 23 patients with euthyroid goiter, 9 patients with hypothyroidism and 17 patients with hyperthyroidism were injected with 400 micrograms thyroliberin (thyrotropin releasing hormone, TRH). The documented side effects were the same in all the 4 groups studied. Subjective symptoms such as flushing, nausea, urinary urgency, dizziness and headache in decreasing sequence were mentioned by 86% of subjects. Shortly after thyroliberin injection, a mean increase of 26 +/- 13 mm Hg for systolic and 14 +/- 6 mm Hg for diastolic blood pressure as well as an increased heart rate by 7.2 +/- 6.6 min-1 was demonstrated. Plasma catecholamines were lowered in patients with euthyroid goiter and hyperthyroidism and raised in patients with hypothyroidism, compared with the controls. Thyroliberin administration was associated with an activation of the sympathoadrenal system. The increments in plasma epinephrine and norepinephrine concentrations were proportional to initial values, but were insufficient to affect blood pressure. The mean increase of 28% for plasma epinephrine and 21% for norepinephrine were maximal in the second to the forth minute, where subjective symptoms, blood pressure and heart rate were already decreasing. In view of the rapid onset of the subjective symptoms as well as the chronotropic and the pressor response, thyroliberin may partly exert these effects centrally or directly on the vascular system, independently of catecholamines. Since individual systolic blood pressure increased by as much as 64 mm Hg, caution is advised in selecting patients with risk factors for testing.

Adult↗

Problems of quantitative urine analysis.

Quantitative determinations of various analytes in urine represent only a small part of all analyses performed in the routine clinical chemistry laboratory. Consequently, analytical as well as pre-analytical problems are less often considered in urine analysis. In the first part of this paper, pre-analytical factors affecting quantitative determinations are discussed, e.g., physical activity, posture, circadian rhythms, different solubilities of the various substances, errors in urine collecting, or drug effects. Subsequently, aspects of linearity and specificity of the routine determinations will be illustrated with special consideration given to protein, calcium, and enzyme determinations as well as some specialized measurements, e.g., porphyrins, catecholamines and their metabolites, or 5-hydroxyindole-acetic acid. Effects of pre-analytical and analytical factors on intra-assay and between-assay variations found in urine analysis are discussed. Using the results of surveys, it is shown that the standardization of methods as well as the use of suitable standards are mandatory for an effective amelioration of the present quality of quantitative urine analysis.

Calcium↗

Plasma catecholamines and alpha- and beta-adrenoceptors in circulating blood cells in patients on continuous ambulatory peritoneal dialysis.

Autonomic system dysfunction could be the cause of postural hypotension seen in patients on continuous ambulatory peritoneal dialysis (CAPD). To verify this hypothesis, we examined the alpha 2- and beta 2-adrenoceptors on blood cells after 1/2 h in the resting supine position with the peritoneal cavity filled for 2-3 h, as well as the response of plasma norepinephrine (NE), heart rate (HR) and mean arterial blood pressure (MAP) to 10 min of standing. Supine free and particularly conjugated NE levels were significantly higher in all uremic patients compared with controls. The postural test induced similar increases of MAP and HR in 8 diabetic, 11 nondiabetic patients and 23 controls, whereas 4 diabetic patients became hypotensive. Orthostasis caused a mean free NE increment of only 0.5 nmol/l in the latter patient group with mean NE responses of 1.45-1.65 nmol/l in the former 3 groups. The densities of platelet alpha 2-adrenoceptors (assessed by [3H] yohimbine binding) and of mononuclear leucocyte (MNL) beta 2-adrenoceptors determined by (-) (125I) iodocyanopindolol binding amounted to 160 +/- 50 and 1600 +/- 520 binding sites/cell, respectively, in controls and were unchanged in patients without postural hypotension. The 4 diabetic patients suffering from postural hypotension showed numerically higher beta 2-receptor numbers (2080 binding sites/cell), significantly increased alpha 2-receptor densities (280 binding sites/cell, p less than 0.05) and significantly increased MNL isoproterenol-stimulated adenylate cyclase activities (38 vs 24 pmol cAMP/10(6) MNL/10 min in controls, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 1↗

Plasma free and conjugated catecholamines in clinical disorders.

Plasma free and sulfoconjugated norepinephrine (NE), epinephrine (E) and dopamine (DA) concentrations measured in patients with thrombocytopenia or thrombocytosis, in newborns and pregnant women were not statistically different from values determined in 41 healthy volunteers. The percentage free to total NE, E and DA was 30 +/- 10%, 35 +/- 11% and 1.5 +/- 1.1% (mean +/- SE) in the controls, resp; not different from the previously described patients or from patients with liver failure who showed significantly higher free and conjugated NE and E levels when compared with controls (p less than 0.01, resp.). Conjugated catecholamine (CA) levels from the femoral artery and from multiple sites in the venous system sampled in patients undergoing intracardiac measurements were identical. The data suggest that sulfation of CA may not be simply ascribed to platelets, to the liver, to vascular beds, or to organs along the vena cava including the adrenal glands. The parallel increase of free and conjugated NE with age in healthy controls, as well as the unchanged degree of conjugation in patients with increased spillover of NE and E caused by a pheochromocytoma or by a heart attack, suggest that there is a balance between free and sulfated CA. A normal ratio of free to conjugated NE and E observed in patients receiving high dosage DA infusion further indicates that there is an adequate sulfate supply and no apparent substrate inhibition of the conjugation process. Because the percentage free of total NE, E and DA were significantly lower in patients in the hypothyroid state when compared with controls (p less than 0.01, resp.), hypothyroidism may affect the balance of free to conjugated CA in a yet unknown way.

Adolescent↗

Free and conjugated catecholamines in human plasma during physical exercise.

To investigate changes of free and sulfoconjugated catecholamines in response to alterations in sympatho-adrenal activity, free and conjugated noradrenaline, adrenaline and dopamine were determined radioenzymatically in plasma of 49 subjects. During brief vigorous bicycle exercise (8 min, maximal heart rate: 177 beats/min) mean free noradrenaline and adrenaline values of 2.0 and 0.51 nmol/l at rest, increased to 6.7 and 2 nmol/l (P less than 0.001) respectively, at the maximal workload of 200 watt, whereas conjugated noradrenaline and adrenaline decreased from 3.4 and 0.8 nmol/l to 2.1 and 0.4 nmol/l (P less than 0.001) respectively. In the tenth min of the recovery period basal free and conjugated noradrenaline and adrenaline levels were measured. The moderate stress of a steam bath (20 min, maximal heart rate: 131 beats/min) doubled free noradrenaline and adrenaline levels. However, conjugated noradrenaline and adrenaline concentrations remained unchanged. The increase in free catecholamine values during an exhausting cross-country march over 20 km was associated with an accumulation of sulfated catecholamines. After a rest of 30 min free noradrenaline and adrenaline reached basal values, whereas conjugated noradrenaline and adrenaline remained elevated by 64 and 70% respectively, compared to pre-exercise concentrations. It was concluded that conjugated noradrenaline and adrenaline may be used as pools for free noradrenaline and adrenaline during brief vigorous exercise. In addition, they may also be indicators of chronic activation of the sympatho-adrenal system.

Adult↗

Determination of catecholamines in plasma by HPLC and amperometric detection. Comparison with a radioenzymatic method.

The determination of norepinephrine and epinephrine in plasma by HPLC with amperometric detection was modified, giving detection limits of 25 ng/l for norepinephrine and epinephrine, respectively, using 1 ml plasma. In order to achieve this sensitivity, it was necessary to minimize the background noise by modification of instrumentation and specimen handling. Particularly important was the extra purification of the reagents, the application of micro-bore HPLC, the enzymatic cleavage of uric acid and temperature control of the amperometric cell and the amplifier. Comparison of the present method with the radioenzymatic determination of catecholamines resulted in coefficients of correlation of r = 0.924 and 0.919 for norepinephrine and epinephrine, resp. (n = 38). The concentrations of the 38 different samples used for the comparison were in the physiological range.

Catecholamines↗

Alpha- and beta-adrenergic receptor activity in circulating blood cells of patients with phaeochromocytoma: effects of adrenalectomy.

In many tissues adrenergic responsiveness may be impaired by chronic exposure to adrenergic agonists. We examined the effects of high levels of circulating norepinephrine and epinephrine to alpha 2- and beta 2-adrenoceptors on platelets and mononuclear leucocytes (MNL) of patients with phaeochromocytoma. When compared with controls the density of beta 2-receptors prior to removal of the tumour was diminished by 67% (500 +/- 160 sites/cell, n = 7 vs 1500 +/- 350 sites/cell, n = 29; P less than 0.001). Binding affinities for [3H]dihydroalprenolol (apparent KD = 0.45 +/- 0.16 nmol/l in phaeochromocytoma, 0.52 +/- 0.19 nmol/l in controls) were not significantly different in MNL preparations from the two groups. MNL adenylate cyclase activities in response to 10 mumol/l (-) isoproterenol was lower in the patients (7.5 vs 22 pmol cAMP/10(6) MNL/10 min; P less than 0.001). Conversely, the number of alpha 2-adrenoceptors on platelets and the affinity of these receptors for [3H]yohimbine did not differ between patients and controls. Ensuing adrenalectomy the regeneration of the beta-adrenergic cAMP-system results from a two-phase process. A prompt but moderate restoration was followed by a gradual rise to the normal range within about 1 to 2 months indicating the dynamic character of the beta 2-adrenoceptor cAMP-system in MNL. We conclude that the downregulation observed in MNL, which appears not to be operative in human platelets, represents only one mechanism of feedback control in the sympatho-adrenal-system protecting tissues from prolonged stimulation by excessive catecholamines.

Adrenal Gland Neoplasms↗

[Routine clinical chemical analysis with prepared reagent carriers].

The determination of glucose, uric acid, urea, triglycerides, cholesterol, sodium, and potassium was investigated using an Ektachem DT 60 and the Ektachem DTE-module. The coefficients of variation ranged from 0.5 to 5.3% for within run and from 1.1 to 4.7% for within day precision. The deviations of the measured values from the assigned values (determined by gas chromatography and mass spectrometry, or by interlaboratory surveys were less than 5%. The determination of urea in control samples was influenced by matrix effects, but not the analysis of patients samples. The comparative analysis of patient samples with routine methods and multilayer reagent carriers showed good agreement. The linear coefficients of correlation ranged from 0.9318 (sodium) to 0.9945 (triglycerides). The analyser is easy to use and has been proved to be very reliable. The throughput of 65 substrate and 15 electrolyte determinations per hour is sufficient for the medical practitioner or small laboratories.

Blood Chemical Analysis↗