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Biomedical subjects

E Knoll

Publications and source records attributed to E Knoll.

At least 55 records · Page 3Linked to original sources

Determination of urinary vanilmandelic acid and homovanillic acid by high performance liquid chromatography with amperometric detection.

A method was developed for the simultaneous determination of urinary vanilmandelic acid and homovanillic acid, which included a two step prepurification and a reversed-phase high-performance liquid chromatography with amperometric detection. Conditions were evaluated for performing measurements with the amperometric detector free from electric interference. The method was linear between 2.5 and 100 mumol/l vanilmandelic acid and homovanillic acid with good precision (CV always less than 10%). The correlation between the present determination of vanilmandelic acid and the procedure of Pisano et al. ((1962) Clin. Chim. Acta 7, 285-291) was very good (r = 0.931). No interfering substances could be detected.

Chromatography, High Pressure Liquid↗

The determination of calcium, glucose, urea and uric acid using the Kodak EKTACHEM multilayer film technology: an evaluation.

Calcium, glucose, urea and uric acid determinations on the "'Kodak Ektachem Four Chemistry Analyzer" were tested for precision and an estimation of the accuracy was performed with our laboratory routine methods using patients' sera and proficiency fluids. Precision -- examined over a period of six weeks -- was very good. Even the very stringent claim of the College of American Pathologists (CAP) -- that analytical dispersion should be less than 1/16th of the normal range -- was fulfilled in almost all control samples. The results from patients' sera measured using both the Ektachem and the routine laboratory methods showed very good correlation. Proficiency fluids tested for calcium, glucose and uric acid all resulted in values well within the assigned interval. Some negative bias was noted for the urea determination however. This could not be completely eliminated even though the samples had been reconstituted with a bicarbonate solution according to the manufacturer's instructions. The linear range of the four determinations was checked: calcium is linear up to 4.2 mmol/l, glucose up to 33 mmol/l, urea up to 60 mmol/l and uric acid up to 1370 mumol/l. Our results confirmed the long-term stability of analyzer and slides to be so high that one calibration per week is sufficient.

Blood Glucose↗

Urinary excretion of alanine-aminopeptidase and N-acetyl-beta-D-glucosaminidase during sequential combination chemotherapy.

The urinary excretion of alanine aminopeptidase (EC 3.4.11.2) and N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30) was determined in 23 patients with testicular cancer during sequential combination chemotherapy with vinblastine/bleomycin and doxorubicin/cis-platinum. Increases in enzyme excretion were more often noticed during therapy with vinblastine/bleomycin than with doxorubicin/cis-platinum. Moreover, the rises during vinblastine/bleomycin therapy were more pronounced. The enzyme activities varied from the normal range up to the 14-fold of the upper limit of the normal range. With few exceptions, enzyme excretions returned to normal or slightly elevated values before the subsequent course. No renal insufficiency could be detected with the commonly used parameters of renal function such as serum creatinine concentrations and creatinine clearance values, which were determined at irregular intervals.

Acetylglucosaminidase↗

Circadian rhythm of catecholamines, cortisol and prolactin is altered in patients with apallic syndrome in comparison with normal volunteers.

Circadian rhythms of catecholamines, cortisol and prolactin were investigated in 4 healthy subjects and in 6 patients suffering from an apallic syndrome. The clinical picture of this syndrome is characterized by disturbed consciousness (coma vigile), suspension of the sleeping and waking rhythm, lack of emotional reactions and appearance of primitive motor patterns. With the exception of dopamine a pronounced circadian rhythm was found in the control group for all investigated parameters. Catecholamines and cortisol showed a good correlation in the temporal pattern of plasma concentrations and urinary excreted amounts. In all apallic patients the circadian rhythm of prolactin was abolished. Only in one patient a rhythm of catecholamines and in 2 patients a rhythm of cortisol was still detectable. The data may indicate that the episodic nature of hormone secretion was essentially unaffected by the apallic syndrome. These results are regarded as an indication that endogenous, centrally controlled processes participate in circadian rhythms.

Adolescent↗

Altered circadian rhythm of catecholamines in patients with apallic syndrome.

Circadian rhythms of catecholamines were investigated in 4 healthy subjects and in 6 patients suffering from an apallic syndrome. The clinical picture of this syndrome is characterized by disturbed consciousness (coma vigile), by suspension of the sleeping and waking rhythm, by lack of emotional reactions and by appearance of primitive motor patterns. 5 of the 6 apallic patients showed an abolished rhythmicity compared with the control group. These results were interpreted as an indication that endogenous, centrally controlled processes are the cause of circadian rhythms.

Adolescent↗

Urinary excretion of N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase in patients receiving amikacin or cis-platinum.

Urinary excretion of alanine aminopeptidase (EC 3.4.11.2) and N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30) was determined for 25-70 days in five patients receiving cis-platinum and for 8-53 days in six patients receiving amikacin. This study was performed to investigate if the excretion of urinary enzymes represents a sensitive parameter for the early detection of toxic kidney damage. The determination of N-acetyl-beta-D-glucosaminidase was carried out by the method of Knoll et al. [13]. The procedure of Mondorf et al. [14] for the estimation of alanine aminopeptidase activity was adapted to the Gemsaec Fast-Analyzer. In both patient groups an increase in the excretion of the two enzyme activities could be demonstrated. In patients receiving amikacin, the excretion of alanine aminopeptidase was always higher than that of N-acetyl-beta-D-glucosaminidase, whereas in three patients receiving cis-platinum it was the opposite. In two cis-platinum patients the excretion of both enzymes was of the same size. The changes during amikacin therapy seem to be reversible, whereas in four cis-platinum patients these changes seemed to be partly irreversible. Serum creatinine concentration was less sensitive than the urinary enzyme excretion for detection of kidney damage.

Acetylglucosaminidase↗

Preparation of antibodies to catecholamines and metabolites--syntheses of various immunogens and characterization of the resulting antibodies.

The synthesis of antigens of the haptens p-tyramine, octopamine, synephrine, dopamine, normetanephrine, beta-(3,4-dichlorophenyl)-ethylamine and 3-fluoro-tyramine is described. The coupling of the haptens to the carrier protein was performed either via the side chain by means of succinic anhydride, or through the phenolic ring via an aminomethyl group which was introduced by a Mannich reaction. Antisera to these haptens were produced in rabbits by immunization with these antigens. The antisera were characterized by determination of titer and specificity (p-tyramine, synephrine, normetanephrine). The possibility is discussed of using antisera to p-hydroxyphenylethylamine for a radioimmunological determination of catecholamines.

Animals↗

[Circadian rhythm of free catecholamine excretion in disturbed adrenal function (author's transl)].

The daily time course of urinary catecholamine excretion was determined for hyperactivity of the sympathoadrenal system (3 phaeochromocytomas, 1 neuroblastoma), disturbed adrenal function (M. Addison and partial adrenal insufficiency), bilateral adrenalectomy (one patient), in 8 healthy patients receiving dexamethasone, and in a control group. All groups showed a circadian rhythm of catecholamine excretion. In the patients with phaeochromocytoma, the excretion of catecholamines and vanilmandelic acid showed a shift of phase compared with the control group. In patients with hyperfunction of the sympathoadrenal system, catecholamines and vanilmandelic acid fluctuated with similar amplitudes, whereas in healthy patients vanilmandelic acid and dopamine showed much smaller fluctuations of concentration than adrenaline and noradrenaline.

Adrenal Gland Diseases↗

[12 years Austrian newborn screening for inborn errors of metabolism. Results with special reference to phenylketonuria, hyperphenylalaninemia and histidinemia (author's transl)].

The Austrian Screening Program performed during the last 12 years 5,833.381 tests in 1,003.841 newborns to detect at last 10 different disorders. 225 cases were uncovered: 81 PKU, 1 Dihydropteridine-Reductase-Deficiency, 37 Hyperphenylalaninemias of long duration, 23 Galactosemias by Transferase deficiency, 6 by Kinase deficiency, 1 Leucinosis, 1 Homocystinuria, 54 Histidinemias, 2 Arginino-Succinic-Acidurias, 3 alpha-1-Antitrypsin-Inhibitor-Deficiencies, 15 Hypothyroidism as well as 1 Phosphoglucomutase-Deficiency. Since 1976 97% of all live births were tested. Except in Hypothyroidism in Austria also treatment and follow-up are centralized. This makes a higher treatment quality and important observations possible. In PKU-patients there is a decline in EQ/IQ between 1 and 6 to 8 years of age of 13 points in average (105--92). This decline can not be correlated with treatment introduction age (26.4 days) and treatment quality. Since also the parents IQ's are significantly below the IQ's of a recent control group and mothers IQ are paralleling the IQ's of their PKU children the decline seems to be a phenylalanine-blood-level-independent phenomenon. Also one quarter of the patients with Histidinemia shows the same IQ decline. The difference between Bühler-Hetzer and Kramer results at 4 years of age seem to have prognostic value. Comparison for 1978 of the expenses of the total screening plus the one of diet in 59 PKU patients already psychometrically tested (average IQ 100) with the expense for institutionalisation of the same 59 shows the former 5 million A.S. lower.

Austria↗

[Psychometry and psychological observations in early treated children with phenylketonuria (PKU) during 12 years (author's transl)].

Among 81 PKU's uncovered until 1978/12/31 63 were 1 to more than 8 years old so at least once up to 4 times psychometrically examined. Although the IQ's at 8 years were still in the normal rang there was a slight but between 6 and 8 years statistically significant (p less than 0.01) decline in IQ. There is no correlation between this decline and the diet introduction age (26--29, average 26,4 days) nor the diet discontinuation age (4 to 8 years) and the predominantly good diet quality. But there were relations to the parental IQ. It seems remarkable that the centers of London and Warschau report declines of the same extent at approximately the same ages in spite of different diet discontinuation ages. The IQ losses in the patients derive almost totally from losses in the verbal part of the tests. Also the slight but statistically significant IQ deficits demonstrated in heterozygotes for PKU (parents) arise almost entirely from the verbal quotient. It is supposed that both observations are phenylalanine blood level independent phenomena. The demonstration of statistically highly significant augmentations of intracellular phenylalanine (and tyrosine) in heterozygotes and homozygotes for PKU may indicate an explanation. Our early treated children with PKU show the same weakness in concentration, perseverance and cognitive abilities (mathematics, orthography, picture coordination) as observed by other centers. These disabilities are largely IQ independent, influence school work adversely but can be improved by psychological promotion. Children with hyperphenylalaninemia do not show the slight decline in IQ nor the specific disabilities.

Age Factors↗

[Hypergalactosemia in newborns as uncovered by the Austrian screening program in 12 years (author's transl)].

The Austrian Screening Program examined during 12 years 1,002.424 newborns and uncovered 23 cases of Galactosemia by Transferase deficiency, 6 by Kinase deficiency as well as 1 case of Phosphoglucomutase deficiency, 1 of porto-caval shunt and 1 congenital liver cirrhosis. Among the 23 Transferase deficiencies 18 took a fulminating course and 8 of these died. Since introduction of exchange transfusion as emergency treatment and acceleration of the screening procedure only 2 among 11 have died. Half of all Galactosemia cases, Transferase and Kinase, show already at the first examination (2. week) a cataract which however is reversible. In contrast to Kinase deficiency all cases of Transferase deficiency exhibit mental retardation if they grow older. Since treatment is early (9, 7 days), easy and the IQ already at 4 years 10 points below that of treated PKU's of same age a congenital brain damage has to be considered. Galactosemia by Transferase deficiency is in Western-Austria significantly more frequent than in Eastern-Austria. 17 boys compare with 6 girls. Among 6 cases of Galactosemia by Kinase deficiency 1 belonged to a Gippsy and 2 to Yugoslavian guest worker families. The 23 cases with Transferase deficiency had 45 siblings among whom 11 also were galactosemic. In 8 sibships the clinical course was of the same typ, but in 1 family one child showed the fulminating the other the subacute course.

Austria↗

Single-isotope enzymatic derivative method for measuring catecholamines in human plasma.

The radioenzymatic determination of plasma catecholamines with a modification of the method of da Prada & Zürcher ((1976), Life Sci 19, 1161-1174) is described. The several reaction steps were optimized with respect to the quantities of substrate and enzyme, and reaction time. There were particular methodological difficulties concerning the blanks, which were determined by using sodium metaperiodate-oxidized plasma. The reliability criteria of the method were determined. Coefficients of variation between 3.4 and 8.6% were found for the intra-assay variability of 10 pg of norepinephrine and 3 pg of epinephrine or dopamine, resp. The recoveries o the three catecholamines ranged from 88-93%. The detection limits were calculated from the standard deviation of the blanks and amounted to 12 ng/l (norepinephrine), 6 ng/l (dopamine) and 3 ng/l (epinephrine). The method was used for the analysis of plasma samples from patients. In a further investigation we examined the stability of plasma catecholamines stored at different temperatures. It was found that samples can be stored for 1-2 hours at room temperature and for several weeks at -27 degrees C without losses in catecholamine content.

Animals↗

[Diurnal variation of the elevated acid phosphatase activity in cases of prostate carcinoma (author's transl)].

The diurnal rhythm of total acid phosphatase and prostatic phosphatase activities was investigated in patients with prostate carcinoma. In these patients, the activities of total acid phosphatase, the tartrate-sensitive fraction of acid phosphatase, and lactate dehydrogenase decrease after therapy, whereas the activity of alkaline phosphatase increases. In all patients with prostate carcinoma, the total and tartrate-inhibited acid phosphatase, and the level of cortisol show a diurnal rhythm before therapy, with a minimum at night. In one patient, after orchiectomy, the cortisol rhythm remained unchanged, but the daily phosphatase variation was absent. Diurnal variations of lactate dehydrogenase and alkaline phosphatase were also observed in 2 patients without prostate carcinoma, but with elevated levels of these enzymes.

Acid Phosphatase↗

[Comparative study of the diagnostic value of disc electrophoresis of urinary proteins and measurement of the excretion of N-acetylglucosaminidase for the detection of renal tubule damage in chronic polyarthritis (author's transl)].

A method is described for the determination of the enzyme N-acetyl-beta-D-glucosaminidase in gel-filtered urine. The individual reaction parameters were tested, and the reliability of the method was determined. The stability of the enzyme in urine was investigated at different temperatures over a 6 week period. The excretion of N-acetyl-beta-D-glucosaminidase, like the analysis of urinary proteins by disc electrophoresis, is a sensitive parameter for renal damage. The two methods were compared, using 50 random urine samples from patients with chronic polyarthritis; both methods were found to have equal diagnostic value.

Acetylglucosaminidase↗

Diurnal variations of estriol and cortisol in serum and urine in late pregnancy with and without fenoterol-therapy.

The serum concentration of unconjugated estriol, total estriol, cortisol in one hour intervals and the urinary excretion of total estrogens and cortisol in three hour intervals was determined in eleven apparently healthy women between 26 and 40 weeks of gestation. They were divided into two groups, in order to study the influence of Fenoterol treatment on the daily variation of the measured parameters. Six patients were treated with Fenoterol and five patients received no medication. Between the two groups no statistical differences could be detected for the measured parameters. Regular and marked diurnal variations in cortisol have been observed, whereas total and unconjugated estriol showed small and irregular daily changes. These daily variations of "estriol" were of the same magnitude as the two-fold methodical standard deviation. For this reason it is not necessary to standardize the sampling time.

Circadian Rhythm↗

3,4-Dimethoxyphenylethylamine excretion of normals and schizophrenics, behaviour during total fasting.

A specific and sensitive radioimmunoassay for the determination of 3,4-dimethoxyphenylethylamine (3,4-DMPEA) in urine was developed. In 5 fasting healthy volunteers excretion of 3,4-DMPEA was not diminished, indicating that this substance can be regarded as an endogenous metabolite. In addition, the time profile of the excretion of 3,4-DMPEA was measured in one patient during total fasting. In 25 patients with schizophrenic psychoses, 9 psychiatric patients without schizophrenia and 80 control patients excretion of 3,4-DMPEA was compared. No significant differences could be observed between these three groups.

Adult↗

Methodical investigation of the production of antibodies towards 3,4-dimethoxyphenylethylamine.

In this study the synthesis of various antigens from 3,4-dimethoxyphenylethylamine (3,4-DMPEA) is described. Antigen A was formed by coupling the acylated side chain of 3,4-DMPEA to the protein, while antigen B was synthesized by introducing an acylated amino group to the benzene ring and linking this reactive group to the protein. With antigen A an antiserum with a titer of 1 : 16000 could be raised, while with antigen B coupled to human albumin and bovine gamma-globulin the antiserum had a titer of 1 :1000 and 1 : 4000. Antibodies formed by immunization with antigen A exhibited a high specificity for substituents of the benzene ring, but were less specific for substituents of the side chain. Antibodies formed by treatment with the antigen B were specific for both kinds of substituents. So far, it has not been possible to harvest any specific antibodies towards the corresponding antigens of dopamine.

Animals↗

[Kinetic assay of creatinine with the Gemsaec-Fast-Analyzer; comparison with the Fuller's earth method (author's transl].

A kinetic method is described for the determination of creatinine in serum. The method is adapted for use with Gemsaec-Fast-Analyzer. The reliability criteria of the method are reported. The only interfering substance is bilirubin, which, when present in elevated concentrations, causes an apparent decrease in the level of creatinine. This interference can be avoided by treating the sample with Fuller's earth prior to the creatinine determination. 72 sera were analysed by the kinetic method and by the Fuller's earth method without deproteinization (5). There was excellent agreement between the two methods (y=1.011 x--0.8222;r=0.9970).

Bilirubin↗