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Biomedical subjects

K Bauer

Publications and source records attributed to K Bauer.

At least 163 records · Page 9Linked to original sources

Creatine kinase determination: a European evaluation of the creatine kinase determination in serum, plasma and whole blood with the Reflotron system.

We evaluated a new dry-reagent carrier system for the determination of creatine kinase (EC 2.7.3.2) activity, Reflotron CK, with special attention to analytical performance with whole blood. We found a good within series imprecision. The median coefficient of variation was 3.1% for Reflotron CK (blood, serum and plasma) and 0.9% for the automatic analysers (serum and plasma only). The between-days imprecision with Reflotron CK (median CV: less than or equal to 3%) was similar to that for the comparison method on different analysers. Fresh samples of human blood, plasma and serum were examined by Reflotron CK and by a N-acetylcysteine activated creatine kinase method in six different clinical laboratories and in the Evaluation Department of Boehringer Mannheim GmbH. The correlation between these methods was excellent (r greater than or equal to 0.99), the median systematic deviation (bias) for all samples being smaller than -5%. Haematocrits between 0.25 and 0.50, haemolysis up to 6 g/l haemoglobin, and icteric samples with bilirubin concentrations up to 0.2 g/l showed no interference. No drug in therapeutic concentration was found to affect the Reflotron CK results; ascorbic acid, calcium dobesilate and sulphamethoxazole lowered the values only when present in high concentrations. Reflotron CK may be considered as a suitable alternative for decentralized testing sites, especially in situations where creatine kinase results are needed quickly.

Autoanalysis↗

[Postnatal weight loss in ventilated premature infants below 1500 g: significance of renal and extra-renal fluid loss].

In 9 ventilated preterm infants (birth weight 810-1310 g, gestational age 26-30 weeks) we measured total body water (D2O dilution), extracellular volume (sucrose dilution) and renal function parameters at birth and when postnatal weight loss exceeded 5% of birth weight together with day to day changes of weight, fluid balance, and serum electrolytes. A significant postnatal weight loss (-89 +/- 47 g) occurred together with a reduction of total body water (-102 +/- 95 ml) and extracellular volume (-98 +/- 59 ml) in the first three days of life. The intracellular volume did not change. At the same time fluid balance was negative due to a high extrarenal water loss on day 1 and an increasing diuresis on the following days. The serum sodium concentration remained unchanged during postnatal water loss, because the negative fluid balance was accompanied by a negative sodium balance.

Birth Weight↗

Flow cytometric DNA analysis of normal and pathologic parathyroid glands.

Assessment of cellular DNA content and cell cycle analysis by flow cytometry has been useful in predicting patient survival and the malignant potential of many neoplasms. In this study, we analyzed the DNA content and cell cycle distribution of 12 parathyroid adenomas, 15 carcinomas, 5 secondary hyperplasias, and 14 normal parathyroid glands. Appropriate areas demonstrating the pathologic changes were dissociated from paraffin-embedded, formaldehyde-fixed tissue for this purpose. All the cells from normal glands were diploid with mean and median S-phase fractions of 1.2% (range, 0.3-2.7%). Of the 18 glands from five patients with secondary hyperplasia, 4 (22%) had some cells which were aneuploid (from three patients), and 14 (78%) had only cells with a diploid DNA content. Mean and median S-phase fractions were 0.8% (range, 0.3-1.5%). One (8%) of the adenomas was tetraploid, 3 (25%) were aneuploid, and 8 (67%) were diploid. The mean S-phase fraction was 1.5% (range, 0.3-3.8%). Four (27%) of the carcinomas had tetraploid cells, 6 (40%) had aneuploid cells, and 5 (33%) had only diploid cells. Carcinomas had a mean S-phase fraction of 6.0% (median, 5.3%; range, 1.4-14.1%). This study indicates that DNA aneuploidy or tetraploidy may be present in many abnormal parathyroid entities, but not in normal parathyroids. Proliferative activity when considered with the DNA index may be a helpful adjunct in separating carcinomas from adenomas or hyperplasias.

Adenoma↗

Double-blind randomized clinical trial on imidazole salicylate vs ibuprofen in osteoarthritis.

Imidazole salicylate (750 mg t.i.d.) was compared with ibuprofen (400 mg t.i.d.) in a 60-day double-blind parallel group clinical trial in 31 patients with osteoarthritis. Both drugs were effective in relieving joint pain and in reducing the duration of morning stiffness. A statistically significant reduction of the severity of these symptoms was observed already one week after the start of treatment, lasting until the end of the study. No significant differences in efficacy were demonstrated between the two drugs throughout the trial. The systemic tolerability, assessed by changes in tests of hematological, liver and kidney function, urinalysis and faecal occult blood was excellent with both treatments. The incidence of side effects (mostly gastrointestinal complaints) was fairly low in both groups, and less severe in the group treated with imidazole salicylate.

Adult↗

Pulmonary effects of long-term beta 2-blockade in healthy subjects: comparative study of metoprolol OROS.

The effects on airway response of metoprolol OROS (oral osmotic) and three other long-acting beta-adrenoceptor blockers were studied. This was a placebo-controlled, randomized, five-period, single-blind, crossover trial in 15 healthy volunteers. Bronchial beta-blockade was estimated as the displacement of the salbutamol bronchodilator response of specific airway conductance (SGAW) measured by whole-body plethysmography. Metoprolol OROS (14/190 mg), slow-release (SR) metoprolol (200 mg), atenolol (100 mg), long-acting (LA) propranolol (160 mg), and placebo were given once daily for 7 days. Inhaled salbutamol was administered at peak drug levels in cumulative doses of 12.5 to 800 micrograms on day 5 and in a single dose of 400 micrograms on day 7. On day 5, salbutamol induced significant increases in SGAW in each treatment group. SGAW increased after the single dose of salbutamol on day 7 in all groups and then declined steadily. The highest values were found after placebo and metoprolol OROS, with smaller increases after SR metoprolol, atenolol, and LA propranolol, the latter showing the smallest increase. Therefore, it would appear that under steady-state conditions, beta 2-bronchial receptors are least blocked by metoprolol OROS, followed by SR metoprolol, atenolol, and LA propranolol.

Administration, Oral↗

Low-dose oral contraceptives lower plasma levels of apolipoprotein E.

Three different oral contraceptive preparations were studied before and after a 3 month treatment period with respect to their effects on plasma lipoprotein parameters. A total of 58 healthy women requesting oral contraception were randomly assigned to three groups. Each woman received either monophasic preparations containing ethinylestradiol and desogestrel (M-DG); ethinylestradiol and gestodene (M-GD); or a triphasic preparation of ethinylestradiol and levonorgestrel (T-LN). As has been reported in other studies, the concentrations of total plasma cholesterol and apolipoproteins B and A-IV did not change significantly in any group. HDL cholesterol, triglycerides, apolipoproteins A-I and A-II increased or tended to increase. Despite the effects of the three hormone preparations on these lipoprotein parameters, however, each led to a highly significant decrease in apolipoprotein E plasma levels. Considering the recently reported observations that oral contraceptives increase the hepatic uptake of cholesterol-rich remnants, this decrease in apo-E plasma levels may in women that take oral contraceptives be directly correlated with increased hepatic lipoprotein metabolism.

Adolescent↗

Estimation of extracellular volume in preterm infants less than 1500 g, children, and adults by sucrose dilution.

Extracellular volume can be estimated from the distribution volume of sucrose (Vdsucrose). The purpose of this study was to establish sucrose pharmacokinetics in preterm infants less than 1500 g compared to children and adults and to define an optimal sampling scheme. In five preterm infants, 10 children, and five adults Vdsucrose after a single injection was calculated with the two-compartment model (Vdsucrose-TCM) and with the one-compartment model applied only to the elimination phase of the same concentration-time curve (Vdsucrose-OCM). In preterm infants Vdsucrose-TCM was 417 +/- 45 mL/kg (mean +/- SD). Vdsucrose-OCM was only 3.0 +/- 2.3% higher, because sucrose elimination half-life was on average 250 times longer than distribution half-life. Therefore Vdsucrose-OCM, requiring only four blood samples between 2 to 5 h after injection, gave an adequate estimate of Vdsucrose in preterm infants less than 1500 g. Vdsucrose-TCM in children and adults was 188 +/- 26 and 189 +/- 17 mL/kg, respectively. Vdsucrose-OCM was 10 to 65% higher. Therefore, in children and adults only Vdsucrose-TCM gives a reliable estimate of Vdsucrose. This requires 10 to 15 blood samples. The reduced sampling scheme was used in an extension of the study of preterm infants including five additional infants. Vdsucrose-OCM in the preterm infants was 462 +/- 47 mL/kg at birth and 425 +/- 46 mL/kg at maximal postnatal wt loss. Postnatal wt loss (mean -83 +/- 44 g) was not significantly different from postnatal reduction of Vdsucrose-OCM (mean -82 +/- 56 mL), suggesting that postnatal wt loss mainly represents extracellular fluid loss.

Adolescent↗

Regulation and cellular localization of the membrane-bound thyrotropin-releasing hormone-degrading enzyme in primary cultures of neuronal, glial and adenohypophyseal cells.

Using monolayer cultures from murine brain and reaggregate cell cultures of rat anterior pituitary we observed that TRH (pyroGlu-His-Pro-NH2) added to the culture medium was not taken up by these cells but hydrolyzed at the pyroGlu-His bond by an enzyme obviously located at the cell surface. This enzyme exhibited a high degree of substrate specificity and other characteristics of the membrane-bound TRH-degrading enzyme. Relatively high enzymatic activity was associated with cultured neuronal cells from embryonic rat brain while glial cells were almost devoid of this peptidase activity. Rather low, but significant activity was found on anterior pituitary cell aggregates. In agreement with previous in vivo studies we observed that the TRH-degrading ectoenzyme on adenohypophyseal cells was regulated by estradiol and stringently controlled by T3, but that the activity of the brain enzyme was not. When pituitary cells were separated according to their size and density and established in reaggregate cell culture, a close correlation was always observed between enzyme activity and the distribution of lactotrophic cells regardless of the animal models (eu- and hypothyroid adult male rats) used and the cell fractionation techniques (velocity sedimentation and sequential velocity/buoyant density sedimentation) employed. Such a close correlation was not observed with other cell types, such as the somatotrophic cells, the folliculo-stellate cells, the ACTH-producing AtT20 pituitary cells, or thyrotrophic cells. In conclusion, the high degree of substrate specificity, the tissue-specific regulation, and the very heterogeneous distribution of the TRH-degrading ectoenzyme on brain and pituitary cells strongly support the hypothesis that this enzyme serves very specialized functions in the transmission of TRH signals at specific target sites.

Aminopeptidases↗

Artiodactylan phylogeny: an immunogenetic study based on comparative determinant analysis.

The phylogenetic relationships of major artiodactylan taxa were investigated by means of comparative determinant analysis (CDA). Monospecific antisera against taurine cattle albumin, transferrin, C3 and IgM were used to derive determinant formulas of their homologues in 21 species (plus 12 other mammals for outgroup comparison). Fifteen accepted mutations could be demonstrated in Artiodactyla, permitting recognition of nine immunologically defined species groups. Results with phylogenetically relevant implications include the clear immunogenetic separation of the vicugna from true ruminants, a complex pattern of accepted mutations rendering a genealogical analysis of the principal pecoran radiation difficult, one synapomorphic mutation combining the goitred gazelle with bovines but excluding Caprinae, and the immunological recognition of the three grades of wild cattle evolution. This study demonstrates the suitability of CDA as a tool of phylogenetic systematics above the level of genera.

Albumins↗

Dose related protective effect of azelastine on histamine induced bronchoconstriction in extrinsic asthma.

The effect of single oral doses of the antiallergic agent azelastine hydrochloride (1.1, 2.2 and 4.4 mg) was compared to placebo on airway response to histamine challenge in 12 asymptomatic extrinsic asthmatics with proven bronchial hyperresponsiveness to inhaled histamine in a randomized double-blind crossover trial. All doses of azelastine resulted in a significant protection compared to placebo. The effects of 2.2 and 4.4 mg were equivalent and superior compared to 1.1 mg. A naturally small but statistically significant bronchodilator effect was observed 4 h after the two higher doses of azelastine. Tiredness was reported by two patients, the symptom occurred following each placebo and the active drug.

Airway Resistance↗

One single lysine residue is responsible for the special interaction between polyphosphate and the outer membrane porin PhoE of Escherichia coli.

Site-directed mutagenesis was performed with the phosphate starvation-inducible outer membrane porin PhoE of Escherichia coli K-12 to study the molecular basis of its anion selectivity. Lysines 18, 29, 64, and 125 were replaced by glutamic acids, and the properties of the mutant porins were investigated in in vivo and in vitro experiments. Lipid bilayer experiments showed that all these mutations had no influence on the pore structure because PhoE and the mutants had the same single channel conductance in KCl solution. Selectivity measurements revealed that the mutations changed the ionic selectivity of PhoE, but the change was dependent on the location of the lysine. Replacement of Lys18 and Lys29 by glutamic acid had a relatively small influence. The effect of the Lys64 substitution was somewhat larger, and the effect of the replacement of Lys125 resulted in the most drastic change in selectivity and in the loss of the interaction of PhoE with polyphosphate, whereas the replacement of the other lysines had no effect on the polyphosphate interaction behavior. The results are consistent with the assumption that the charge spot in PhoE consists of only 1 lysine per monomer, located in position 125 of the primary sequence and probably close to the pore interior.

Bacterial Outer Membrane Proteins↗

Antithrombin Chicago, amino acid substitution of arginine 393 to histidine.

Antithrombin Chicago is a functionally inactive antithrombin variant whose inheritance is associated with thrombotic disease. The variant antithrombin was isolated from plasma of the propositus by chromatography on heparin-Sepharose, followed by passage through thrombin-Sepharose to remove the normal antithrombin component that is present. A pool of fragments ("CNBr pool 4") containing the reactive site region was prepared from the reduced and S-carboxymethylated variant by cleavage with cyanogen bromide followed by reverse-phase HPLC. Sequential treatment of CNBr pool 4 with trypsin and V8 protease produced peptides whose molecular masses were then determined by fast atom bombardment mass spectrometry. The variant protein digests were characterised by a reduction of a peptide of mass 1086, corresponding to the normal antithrombin sequence Ala382-Arg393. However, they contained a peptide of mass 1748, which arises when Arg393 is replaced by His in the sequence Ala382-Arg399. It is concluded that the functional and clinical abnormalities of antithrombin Chicago are all probably caused by a single amino acid substitution, Arg393 to His.

Amino Acid Sequence↗

Acute and subchronic effects of low-dose bromocriptine in haloperidol-treated schizophrenics.

The effects of the acute (within 24 hr) and subchronic (21 days) addition of low-dose bromocriptine (2.5 mg/day) were compared to placebo in schizophrenic patients treated concomitantly with haloperidol. After 24 hr patients on bromocriptine (n = 15) showed a mean improvement of 29% in the total score of the Brief Psychiatric Rating Scale (BPRS) as compared to 14% in the placebo group (n = 15) (p less than 0.10). The acute improvement correlated negatively with bromocriptine plasma levels; patients with the highest reduction in BPRS score had the lowest plasma levels (between 50 and 150 pg/ml) at 60, 90, and 120 min after intake. The improvement in the bromocriptine group continued until the 10th day of the trial, when a nonsignificant increase in the total BPRS score took place. Analysis of Variance of the overall BPRS improvement during the 21 days revealed no significant difference between both patient groups. Our results give modest support to the idea of an acute antipsychotic response to low-dose dopamine agonists in neuroleptic-treated patients, but fail to support their clinical usefulness in the subchronic treatment of schizophrenia.

Adult↗

Regulation by dibutyryl cyclic AMP of carnosine synthesis in astroglia-rich primary cultures kept in serum-free medium.

The synthesis of carnosine (beta-Ala-His) by astroglia-rich primary cultures was much higher if the cells were cultivated in Ham's nutrient mixture F-12 than if they were grown in Dulbecco's modified Eagle's medium. Carnosine synthesis was not affected by the presence of insulin, transferrin, phorbol myristate acetate, or dexamethasone. However, dibutyryl cyclic AMP and other agents that can, directly or indirectly, activate cyclic AMP-dependent protein kinases strongly lower the rate of carnosine synthesis. The depression of carnosine synthesis was dependent on the concentration of dibutyryl cyclic AMP. The effect was maximal (approximately 80% inhibition) in cultures preincubated with 1 mM dibutyryl cyclic AMP for 4 days. The adenylate cyclase activator forskolin, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, and 8-bromo-cyclic AMP caused the same depression as dibutyryl cyclic AMP, whereas neither butyrate nor dibutyryl cyclic GMP elicited any effect.

1-Methyl-3-isobutylxanthine↗

Postnatal weight loss in preterm neonates less than 1,500 g is due to isotonic dehydration of the extracellular volume.

Weight, extracellular volume (ECV; distribution volume of sucrose) and renal function were studied in 13 preterm infants at birth (age 6 h (2-12); median, range) and again when postnatal weight loss exceeded 5% of birth weight (age 84 (64-97) h). Gestational age was 28 (26-32) weeks, and birthweight was 1,170 g (810-1,455). The infants were nursed in incubators and mechanically ventilated. Fluid therapy allowed a weight loss of up to 10% of birthweight. Body weight decreased significantly from 1,101 +/- 202 g at birth to 1,016 +/- 198 g at day 3 and ECV from 499 +/- 155 ml to 413 +/- 118 ml. Mean weight loss of 85 +/- 50 g was the same as mean ECV loss of 86 +/- 48 ml, suggesting that postnatal weight loss is water loss from the ECV. Weight loss was preceded by a marked increase in diuresis, exceeding fluid intake on day 2. Creatinine clearance did not change. The increased urine output led to a significant increase of sodium excretion without inducing hyponatremia but resulted in an isotonic reduction of ECV.

Creatinine↗

Calculation of rates of immunologically determined accepted mutations (IDAM) for 6 primate plasma proteins.

The possibility to estimate the rates of immunologically determined accepted mutations (IDAMs) in analogy to accepted point mutation (PAM) rates at the amino acid level is demonstrated for 6 primate plasma proteins. The comparative determinant analysis is described and compared with older techniques. The technique and its limitations are discussed as are the conditions a polypeptide region must fulfill to become an antigenic determinant binding to a specific antibody. IDAM rates obtained this way range between 0.70 and 8.35 per 100 residues and 100 million years. Comparisons between IDAM and PAM rates are given.

Animals↗

[Clinico-pharmacologic study of a new sustained-release oral salbutamol preparation in patients with obstructive airway disease].

A new sustained release preparation of oral salbutamol (8 mg) was compared to salbutamol (8 mg) and placebo in 15 patients suffering from chronic obstructive airways disease in a randomized double-blind cross-over trial. Changes in airways resistance and amplitude of finger tremor as well as subjective assessment of side effects (tremors, unrest, palpitations) revealed a longer lasting effect following the sustained release preparation of salbutamol.

Adult↗

Histopathologic and flow cytometric analysis of adenomatous colonic polyps.

We evaluated the histopathology, DNA content, and proliferative activity of colonic polyps independently. Paraffin-embedded specimens were used as source material. In each case, additional sections were cut at 3 microns and stained with hematoxylin-eosin and trichrome for histopathologic analysis. For DNA analysis and measurement of proliferative activity, the polyp parts were dissected and the nonpolypoid tissue was discarded. The study was limited to those specimens that were received in our department in the years 1972 and 1977. Of the 104 polyps that were submitted for flow cytometric analysis, 36 could not be analyzed owing to excessive debris or insufficient nuclei. DNA aneuploidy was identified in 32% of the cases, with a higher value noted in larger polyps and in severely dysplastic polyps, but these values were not statistically significant. Multiple adenomas from the same patient often showed different DNA histograms. When analyzed according to the percentage of cells in S phase, no significant difference was found in proliferative activity of polyps according to DNA content or size of the polyps. These results suggest that the diagnostic significance of aneuploidy and proliferative activity in polyps must be interpreted with caution.

Adenoma↗