[Side effects of anti-arrhythmia agents aprindine and prajmalium bitartrate, in children].
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Biomedical subjects
Publications and source records attributed to D Palm.
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0.05 ml plasma samples are incubated with 3H-S-adenosylmethionine and catechol-O-methyl-transferase. The resulting methodoxy derivatives are extracted, the extracts separated by high pressure liquid chromatography and the metanephrine fractions collected. Evaluation is performed by liquid scintillation counting of radioactivity in the respective fractions. The following performance criteria are presented: precision, accuracy, detectability (40 pg/ml for adrenaline and noradrenaline, 130 pg/ml for dopamine), linearity and day-by-day variation. Comparison with a standard method shows an excellent correlation for adrenaline and noradrenaline.
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The first attack of hemiplegic migraine occurred in most cases between the 10th and 15th year of life in 14 children (8 boys and 6 girls). Most attacks took place with intervals of 3-6 and 6-12 months. Only rarely did they last longer than 24 hours. Precipitating factors (emotional and physical stress, change of weather, influence of light or heat) were given in 6 cases. As many as 7 children attended higher schools with good or average success. A family history, mainly from the maternal side, existed in 11 cases. Sensory symptoms were demonstrable in all children, motor symptoms in 9 and visual symptoms in 13. Ten children had speech disturbances. Hand, lower arm, cheek and tongue were most frequently involved in sensory and motor symptoms. Out of 9 attacks registered with an EEG severe focal signs (delta or theta-delta foci) were demonstrable contralaterally in all children, in 8 children there were also signs of generalized disturbances.
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55 children suffering from acute lymphoblastic leukemia were treated wih prednisone, vincristin-sulfate, daunorubicine and L-asparaginase (1st month), 6-mercapto-purine, cytosine-arabinoside. cyclophospamide, methotrexate-i.th. and cranial irradiation (2nd month). Maintenance-therapy comprised 6-mercapto-purine, cyclophosphamide and methotrexate-i.v. Serial EEG-examination were done in most of them during the course of treatment. 4 children presented with meningeal leukemia at the time of diagnosis. Their EEGs showed moderate slowing before treatment and at the end of the first month. One of them suffered a focal convulsion two days after the last VCR/daunorubine-injection. All EEG-changes were completely reversible later on. 3 patients showed severe focal EEG-disturbances and convulsions during serious neurological complications (intracranial bleeding, rubella-encephalitis). The remaining patients were free of complications at the time of the EEG-examination. Before therapy 24% of them presented normal findings, 57% slightly and 19% moderately abnormal EEGs. At the end of the first month there was an increase of moderate and severe EEG-slowing to 37% and 23%, only 11% of findings were normal. Improvement during the second month of therapy led to 37% normal and 57% slightly abnormal EEG-findings at its end. After maintenance-therapy of 1/2--1 year duration there were 65% normal EEGs and no moderate and severe disturbances any longer. Quantitative spectral analysis of the EEG in 6 additional children revealed similar changes.
Following the exemplification of the clinical symptoms the EEG findings of 10 attacks of hemiplegic migraine in 6 children are reported on. Characteristically most of these are severe unilateral or focal disturbances. Five times these appeared as delta-activity, two times as theta-delta-activity, and in one case as theta-activity or alpha-reduction. Only once, a diffuse slowing of the background-activity over both hemispheres could be shown. With one exception in addition to the foci simultaneous diffuse changes were recorded in all children, (four times slight, twice slight to moderate and three times moderate to severe). A predominance of one hemisphere was not recognizable. The foci were not localized to one particular region of the brain. Most of the changes had subsided after a few days. In one case a slight focal voltage depression was apparent even after three month of a year.
Previous studies in man have shown that during beta-adrenoceptor blockade physical exercise caused a significantly greater elevation of plasma catecholamines than without blockade. After blockade of beta-adrenoceptors, increased levels of circulating catecholamines should have an unopposed effect on adrenergic alpha-receptors. In order to elucidate such an effect, experiments were performed with 7 trained dogs before and after acute beta-adrenoceptor blockade (0.1 mg/kg (-)-propranolol i. v.). Exercise was performed on a conveyor (10 min, 10 km/h, slope 10%). Besides catecholamine concentrations in plasma, as an index of alpha-receptor-stimulation potassium concentrations in plasma were determined. Immediately after exercise, plasma noradrenaline was increased from 310 to 579 pg/ml, plasma adrenaline from 136 to 222 pg/ml and plasma potassium from 4.23 to 4.6 mmol/l. After beta-adrenoceptor blockade exercise caused a significantly higher increase in plasma noradrenaline from 352 to 755 pg/ml and plasma adrenaline from 172 to 260 pg/ml. Also plasma potassium concentrations were significantly elevated from 4.03 to 5.05 mmol/l. The results indicate an enhanced reflex activation of sympatho-neuronal and sympatho-adrenal mechanisms during exercise after beta-adrenoceptor blockade; the increased concentrations of noradrenaline at the adrenoceptors might reduce the efficiency of beta-blockade. Concomitantly, increased stimulation of alpha-adrenoceptors is elicited, which becomes obvious by an increase of potassium concentration in plasma.
The degree of stimulation of adenylcyclase activity, in membranes from immature red blood cells from rats, brought about by isoprenaline, guanylyl-imidodiphosphate and sodium fluoride is strongly dependent on the basal activity of the enzyme. The inversal relationship between basal activity and the maximal degree of stimulation by (--) isoprenaline, shows an apparent seasonal dependence.
Distances between the subunits in Escherichia coli RNA polymerase (core and holo enzyme) and the rifamycin binding site have been determined using the nonradiative energy transfer technique. The appropriate donor and acceptor labels have been chosen in order to optimize the spectral overlap and maximize the energy transfer. Spacer linked derivatives of rifamycin SV possessing nitrobenzo-oxadiazole groups (energy acceptor) were synthesized for this purpose. The donor label, acetylaminoethylaminonaphthalene sulfonate, was introduced into the intact enzyme, and the subunits were separated. Enzyme molecules selectively labelled on one kind of subunit were produced by mixed reconstitution techniques employing labelled and non labelled subunits. The labelled beta'-subunit could not be prepared in sufficient amounts. Energy transfer distances between the enzyme-bound rifamycin derivative and the subunits were determined to be approximately 5.9 nm for sigma, 7.2 nm for alpha 2 and 6.1 nm for beta.
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During the maturation of red blood cells from rats after stress erythropoiesis, adenyl cyclase activity and beta-adrenoceptor density (pmoles/mg protein) decrease at distinctly different rates suggesting a different turnover of these membrane units.
Using delayed auditory feedback (delay 0.175 s) a standardized form of mental stress was investigated in 8 healthy male volunteers. After a resting period and a period of undelayed reading, the volunteers were exposed for 5 min to the DAF stress. During the DAF period heart rate increased by 10% and systolic and diastolic blood pressure increased by 9% and 18%, respectively. As a measure of acute sympathetic activation, plasma concentrations of norepinephrine and epinephrine rose by 68% and 49%, respectively. The activity od dopamine-beta-hydroxylase in plasma was increased by 25%. From these results it can be concluded that the DAF procedure provides a suitable method for inducing a standardized mental stress in normal subjects, which can be measured as changes in biochemical and cardiovascular variables.
The effects of ketamine anesthesia (3 mg/kg i.v.) on cardiovascular parameters and noradrenaline, adrenaline and dopamine-beta-hydroxylase (DBH) activity in plasma were studied in 12 patients. At 3, 6 and 10 min after induction of anesthesia, a pronounced increase in heart rate (+28%) and in systolic and diastolic blood pressure (+28% and 17% resp.) was observed. Concomitantly noradrenaline and adrenaline concentrations increased significantly from 187 to 415 ng/l and from 97 to 271 ng/l, respectively. DBH-activity in plasma remained almost unchanged. From these results it can be concluded that the well known cardiovascular stimulant effect of ketamine is due to greatly enhanced sympatho-neuronal and sympatho-adrenal activity, presumably brought about by a central mechanism of action of the drug. Furthermore, DBH-activity in plasma appeared not to be a reliable index of sympathetic activity in man.
In 49 children with acute lymphoblastic leukemia serial EEGs were performed during the course of treatment. Therapy in the first four weeks consisted of: Prednisone, vincristine, daunorubicine and L-asparaginase. In the second month 6-mercaptopurine, cytosin-arabinoside, cyclophosphamide, methotrexate-i. th. and cranial irradiation were administered. Maintenance-therapy consisted of 6-mercaptopurine, cyclophosphamide and methotrexate i.v. Before treatment only 24% of patients showed normal EEG-findings, whereas 57% presented sly induced by leukemic infiltrations and partly due to the impaired clinical state. At the end of the first phase of therapy, the combined toxicity of vincristine and L-asparaginase led to the finding of 23% severely and 37% moderately slowed EEGs. Slightly disturbed EEGs were found in 29% and normal ones in 11% of children. Regression occurred duirng the phase of CNS-prophylaxis. At its end 37% of recordings were normal and 57% slightly abnormal. After maintenance-therapy of 1/2 to 1 year duration, there were 65% normal findings. Moderate and severe disorders were no longer demonstrated. Paroxysmal activity developed twice, each during the first phase of therapy and accompnaying convulsions. In both cases we saw slowing of background-activity and signs of increased excitability still months after. In one of these patients, the probable cause was a vincristin-encephalopathy, the cause of the second case remained unknown. EEGs of two furtehr patients with rubella-encephalitis and subarachnoideal hemorrhage exhibited severe unspecific changes.
The concentrations of adrenaline and noradrenaline, and dopamine-beta-hydroxylase in the plasma, and certain haemodynamic parameters, were determined in 14 children undergoing surgical correction of congenital cardiac defects under hypothermia at 30 degrees C and methoxyflurane anaesthesia. During the pre-operative phase of hypothermia at 30 degrees C, the adrenaline levels rose to about 300% of the inital levels, and the noradrenaline levels to about 200%. During the postoperative phase of re-warming at 34 degrees C, a further dysregulative release of catecholamines led to an increase in adrenaline levels to a critical concentration of about 800% of the norm, and in noradrenaline levels of about 400% of the norm. No change was seen in dopamine-beta-hydroxylase activity. Hypothermia thus results in a massive activation of the sympatho-neuronal and sympatho-adrenal systems, which is not prevented by methoxyflurane anaesthesia, and which may endanger the recently operated heart, particularly during the early post-operative period, because of the increased oxygen requirements imposed on the myocardium. In normothermia, on the other hand, methoxyflurane anaesthesia results in only a slight degree of activation of the sympathetic nervous system, which increased only slightly during the post-operative period. Under these conditions, the plasma dopamine-beta-hydroxylase activity remains unchanged. Unlike the changes in plasma catecholamine levels, dopamine-beta-hydroxylase activity cannot be regarded as an index of changes in sympatho-neuronal activity.
By means of the radioactive antagonist ligand (3H)(-) dihydroalprenolol (DHAP) specific binding sites were identified in membrane preparations from red blood cells from rats. These specific sites were characterized as beta-adrenoceptors because of the following reasons: Specific binding of DHAP (in contrast to unspecific binding) was dependent on temperature and time of incubation. Furthermore, specific binding of DHAP showed saturability, temperature-dependent reversibility and high affinity (KD-value of DHAP = 6.51 nM). Specific binding of DHAP was competitively inhibited by beta-adrenergic antagonists (pindolol greater than alprenolol greater than or equal to propranolol greater than practolol) and agonists (isoprenaline greater than adrenaline). The (-) enantiomers of pindolol and isoprenaline showed pronounced higher affinities for the receptor sites than the respective (+) enantiomers. The receptor density in the membrane preparations (pmoles/mg protein) was strongly dependent on the degree of reticulocytosis: The Bmax-values increased more than 4 to 5 fold without alteration of the respective KD-values when reticulocyte counts were enhanced from 3 to 80% treatment of the animals with increasing doses of acetyl phenylhydrazine.