Search PubMed⌕ Search

Biomedical subjects

R Brandt

Publications and source records attributed to R Brandt.

At least 145 records · Page 8Linked to original sources

Is hyperventilation a physiologically significant stimulus for prostaglandin release in the human pulmonary vascular bed?

The influence of hyperventilation on the pulmonary prostaglandin (PG) release was studied in healthy volunteers. Hyperventilation was forced by adding 8% CO2 to the inhaled air and arterial and mixed venous blood was sampled for radioimmunoassays of 6-keto-PGF1 alpha and PGE2. The increased ventilation did not alter the arterio-venous PG concentration differences suggesting that hyperventilation accompanying the activation of chemoreceptors is not a physiologically significant stimulus for the pulmonary PG release in man.

6-Ketoprostaglandin F1 alpha↗

Stimulatory cholinergic effect on the release of antiaggregatory activity into the circulation of cat and man and its modification by beta-adrenergic antagonists.

The release of PGI2-like activity into the circulation in response to cholinergic agonists and modification of this response by beta-adrenergic antagonists was investigated in anaesthetized cats and healthy humans. Antiaggregatory activity in the arterial blood was continuously assayed by measuring platelet aggregation on blood superfused collagen strip. In some of the human experiments, after the administration of the drugs, the conversion of [14C]-arachidonate to [14C]-prostaglandins in the pulmonary vascular bed was studied. Cholinergic agonists stimulated the release of PGI2-like activity into the circulation, which effect was potentiated in cats by beta-adrenergic antagonists. In humans the latter agents did not stimulate the conversion of [14C]-arachidonate to prostaglandins in the pulmonary circulation and, moreover, inhibited the stimulatory cholinergic effect. The results suggest that an interplay between cholinergic and beta-adrenergic mediators may be involved, although in a different way in cats and in humans, in the release of PGI2-like activity into the systemic circulation.

Acetylcholine↗

Mapping of cysteine genes on the chromosome of Pseudomonas aeruginosa PAO.

Three loci coding for different steps in the pathway of cysteine biosynthesis have been mapped by R68.45-mediated coconjugation analysis. The cysteine auxotrophic mutants could be subdivided into sulfite and sulfide-requiring mutants. Sulfide-requiring mutants (cysIV group) were localized at a single position between pyrF and pur-67, while sulfite-requiring mutants (cysI and cysII) mapped at two different regions. The cysI group was also localized between pyrF and pur-67, although more distal to pyrF than the cysIV group. This group included the cys-54 marker, which has been mapped previously. The second group of sulfite-requiring mutants, designated as cysII, was cotransducible with hisI and localized at the end of the PAO chromosomal map. This location was also confirmed for the marker cys-59. The marker cys-59 (which was cotransducible with hisI) was cotransferred by R68.45-mediated conjugations with both the late marker pur-67 and the early marker ilv-226. As the late marker hisI was positioned at about 60-65 min (Herrmann and Günther, in press) the length of the PAO chromosome was estimated to be about 70 min.

Chromosome Mapping↗

Release of prostacyclin from the human pulmonary vascular bed in response to cholinergic stimulation.

The ability of the human pulmonary vascular bed to synthesize prostaglandins (PGs) in response to cholinergic stimulation was investigated in healthy male volunteers. In all of them, except controls, carbaminoylcholine (CCh) was injected subcutaneously at a dose of 5 micrograms/kg. In 3 subjects [1-14C]-labelled arachidonate was then infused at a constant rate into the right atrium between 10 and 15 min after the administration of the drug and the blood from the subclavian artery was sampled simultaneously. The arterial content of [14C]-labelled metabolites was extracted, separated by thin-layer chromatography and quantified using liquid scintillation spectrometry. In 8 other subjects PGI2-like activity after the administration of CCh was assayed in the arterial blood and in 1 subject in the venous blood, using a technique for continuous measurement of platelet aggregation on blood-superfused collagen strip. The major portion of [14C]-activity in the radiochromatograms migrated in parallel with the 6-keto-PGF1 alpha standard. No early defined peaks corresponding to any of the unlabelled PGs D2, E2 or F2 alpha, appeared, but in one chromatogram a minor radiopeak corresponding to authentic thromboxane B2 was observed. Also in the platelet aggregation experiments, 5-15 min after the administration of CCh, a significant increase in the PGI2-like activity was observed in the arterial as well as in the peripheral venous blood, which effect of the drug was abolished by pretreatment with atropine and acetylsalicylic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of propranolol, practolol and atenolol on human platelet thromboxane formation and plasma levels of prostaglandins 6-keto-F1 alpha and E2.

The effects of three different beta-adrenergic blocking drugs, propranolol, practolol and atenolol on platelet thromboxane production and the release of prostacyclin and prostaglandin E2 into the circulation were investigated in healthy volunteers. The beta-adrenergic antagonists were administered intravenously at equipotent doses. The serum TxB2 levels after whole blood clotting and the arterial and venous plasma concentrations of 6-keto-PGF1 alpha and PGE2 were measured before and during a 60 min period after the administration of the drugs, using radioimmunoassay. Practolol and atenolol elicited a significant decrease in platelet thromboxane formation but remained without effect on plasma 6-keto-PGF1 alpha and PGE2 levels. In contrast, propranolol did not influence serum TxB2 concentrations but induced a significant increase in plasma content of 6-keto-PGF1 alpha and PGE2. The results indicate that beta-adrenergic antagonists alter the balance between the proaggregatory, vasoconstricting and antiaggregatory, vasodilating prostanoids in the human cardiovascular system. Although the direction of the action of these drugs seems to differ depending on the selectivity of the beta-adrenoceptor blocking properties the net effect of this action should be beneficial.

6-Ketoprostaglandin F1 alpha↗

Pharmacokinetics of tenoxicam in healthy human volunteers.

Tenoxicam, a thieno-thiazine derivative, belongs to a new chemical class of non-steroidal anti-inflammatory drugs. Single dose kinetics was investigated after intravenous and oral administration to define the disposition and general absorption characteristics of the drug. After intravenous administration of 20 mg tenoxicam to 12 volunteers the time course of the plasma concentrations of unchanged drug followed two-compartment model characteristics. The area under the plasma-concentration time curve in the distribution phase contributed however only 3% or less to the total area. The plasma clearance was low with values ranging from 1.3 to 4.2 ml/min and the volume of distribution Vss was small averaging at 20 to 40% of the total body weight. The median half-life of elimination from the body was found to be 72 hours (range 42 to 100 hours). The disposition was not influenced by sex. Tenoxicam is highly bound to plasma albumin. At pH 7.4 the fraction bound exceeded 99% but was highly dependent on the pH. Plasma protein binding in patients with rheumatic disease was not different from that measured in healthy volunteers. The partitioning of tenoxicam into red blood cells was limited. Erythrocyte concentrations were only 20-30% of the corresponding plasma concentrations. After oral administration of a 20-mg tablet complete and rapid absorption of the drug was observed with maximum plasma levels of 1.7 to 3.6 micrograms/ml reached within 0.5 to 2 hours. Due to the rapid absorption and terminal half-life of the drug its plasma concentration profile after oral administration was very similar to that following intravenous dosing. The pharmacokinetic characteristics of tenoxicam offers a rationale to administer the entire dose in one single portion.

Administration, Oral↗

Effects of beta-blockade on glycogen metabolism in human subjects during exercise.

The effect of beta-blockade on glycogen metabolism during isometric and dynamic exercise in humans has been investigated. Isometric exercise increased the glycogenolytic rate in muscle but had no effect on the cAMP content. Neither the metabolic pattern nor the time of contraction was affected by beta-blockade. Dynamic exercise increased the cAMP content in muscle by about 100%. The cAMP content at rest was significantly reduced after propranolol infusion and did not increase during exercise. Total hexosemonophosphates increased sixfold during exercise but little or no increase occurred after administration of propranolol. The accumulation of lactate in muscle was slightly reduced during exercise following beta-blockade. The fraction of phosphorylase in the alpha form was 22.5% of the total at rest but decreased to 16% at exhaustion. Synthetase I was similarly decreased. During exercise with propranolol phosphorylase alpha decreased further to 3%, whereas synthetase I was unchanged. It is concluded that beta-blockade has no effect on muscle glycogenolysis during isometric contraction but decreases the rate of glycogen degradation during dynamic exercise at high work loads due to changes in the phosphorylase-synthetase system.

Adolescent↗

Effect of posttraumatic epidural analgesia on the cortisol and hyperglycaemic response to surgery.

Plasma cortisol and glucose were measured in 36 patients undergoing abdominal hysterectomy under either general anaesthesia (Group I), epidural analgesia (T4-S5) effective before surgery (Group II) or general anaesthesia plus epidural analgesia (T4-S5) effective from 30 min after initiation of surgery. The results confirmed that epidural analgesia effective before skin incision (Group II) prevented the normal per-and postoperative increase in plasma cortisol and glucose. Patients receiving posttraumatic epidural analgesia (Group III) showed the normal initial increase in plasma cortisol and glucose, but initiation of epidural analgesia immediately broke the stress-response and prevented any further increase in plasma cortisol and glucose. However, although posttraumatic neurogenic blockade inhibited a major part of the stress-response, resting endocrine-metabolic activity was not reestablished, suggesting that once released the endocrine-metabolic response to trauma leads to persistent changes even if further afferent stimuli from the traumatized area are prevented.

Analgesia↗

The effect of physical training in elderly subjects with special reference to energy-rich phosphagens and myoglobin in leg skeletal muscle.

Energy-rich phosphagens and myoglobin were determined in leg skeletal muscles of seven, 61- to 80-year-old, apparently healthy male subjects. The study repeated after the participants had been exercising on an ergometer bicycle twice weekly for 6 weeks. Before training, myoglobin and all intramuscular energy-rich phosphagens were within the range recorded for a larger series of subjects of similar age. When re-examined after training the myoglobin level remained the same but creatine decreased significantly and the ratio between phosphocreatine and total creatine increased. A slight but significant rise was also observed for the ATP/ADP ratio. It is concluded that age-related changes of intramuscular phosphagens in elderly subjects in part might be due to physical inactivity.

Adenosine Diphosphate↗

Effects of concentration-dependent plasma protein binding on ceftriaxone kinetics.

The kinetics of ceftriaxone, a cephalosporin, was studied in six healthy subjects who received bolus injections of 150, 500, and 1,500 mg intravenously in a random crossover fashion. Although total drug concentration time profiles after all doses could be described by biexponential equation, simple compartment analysis was inappropriate because a disproportional increase in the area under the total drug concentration time curves occurred with dose. This resulted in a dose-dependent increase in total systemic clearance (ClTS) from 9.7 ml/min at the 150-mg dose to 13 ml/min at the 1500-mg dose. The dose-dependent changes in ClTS could be explained in terms of the concentration-dependent plasma protein binding of ceftriaxone (fplasma ranging from 0.04 to 0.167), because the area under the free drug concentration time curves (AUCFO-infinity) increased proportionately to dose. Mean total clearance with reference to free (unbound) ceftriaxone (ClFS) was constant at 255 ml/min. Calculated mean renal clearance with reference to free ceftriaxone (ClFR) was 173 ml/min, or slightly more than the average glomerular filtration rate in humans. Mean plasma ceftriaxone t1/2 was not influenced by dose and averaged 8 hr. This biological t1/2 is by far the longest ever for a cephalosporin in healthy subjects.

Adult↗

Studies on kidney function in subjects exposed to organic solvents. IV. Effect on 51-Cr-EDTA clearance.

Glomerular filtration rate (GFR) was studied by measuring the 51-Cr-EDTA clearance with single bolus injection technique in 107 men exposed to styrene, toluene or toluene and xylene in their professions and in 48 non-exposed male controls. The clearance values of the controls were significantly related both to body surface area (BSA) and age. These relations were used to calculate expected clearances for the exposed subjects. The clearances of the exposed subjects were on an average 3.8% higher than expected, according to BSA and age in this group. This divergence was not significant. Thus, no reduction in GFR was found in the subjects exposed to organic solvents.

Adult↗

The effect of fluid deprivation, antidiuretic hormone and forced fluid intake on 51-Cr-EDTA clearance.

The effect of fluid deprivation, antidiuretic hormone (DDAVP) and forced fluid intake on glomerular filtration rate (GFR) was studied in 41 healthy males by determining 51-Cr-EDTA clearance after a single bolus injection. GFR was the same on forced and on free fluid intake. A small, clinically insignificant decrease in GFR (-6.5%), compared to values on free fluid intake, was registered during the periods of fluid deprivation plus DDAVP. There seem to be no objections to combining a clearance study with a concentrating ability test when screening groups of subjects with normal or near normal GFR.

Adult↗

Hepatic gluconeogenesis during halothane anaesthesia in man.

It is known that hepatic gluconeogenesis from lactate and aminoacids is inhibited by halothane in in vitro studies on isolated, perfused livers. In the present work, the effect of halothane anaesthesia on hepatic gluconeogenesis was studied in three volunteers during a constant amino-acid infusion and compared with three control subjects who did not receive any halothane during the amino-acid infusion. Prior to the investigation, all the subjects were on a carbohydrate-poor diet in order to deplete hepatic glucogen stores. During the investigation, hepatic gluconeogenesis was stimulated by a constant amino-acid infusion which caused a slight rise in total hepatic blood flow (THBF), a marked increase in splanchnic oxygen consumption and oxygen extraction, elevation in blood glucose and urea levels and in splanchnic glucose and urea releases. Halothane anaesthesia administered during continued amino-acid infusion caused a reduction in THBF to sub-control values, while the increased oxygen consumption was only slightly reduced, thereby further increasing splanchnic oxygen extraction. Blood glucose and urea levels of the anaesthetized subjects were consistent with those of the control subjects. Splanchnic release of glucose was reduced almost to control values during halothane. However, the release of urea was only slightly reduced. It is concluded that the stimulating effect on hepatic gluconeogenesis caused by the amino-acid infusion was inhibited during halothane anaesthesia, while metabolization of the amino-acids, other than through gluconeogenesis, proceeded without any major changes.

Adult↗

On stability of scintillation detectors.

This paper describes how a photomultiplier tube in a scintillation detector changes pulse height with time, when the detector is exposed to a gamma-emitting source and high dynode voltage. The change in pulse height causes a "drift" of the spectral peaks out of the preadjusted energy window, and errors in counting rate of about 20% are detected. The drift is dependent on the photon flux, the level of the high voltage, and the energy of the source. The effect was not present in all detectors studied. It is thus important to check the stability properties of a detector before use.

Gamma Rays↗

Dog dander allergens. Specificity studies based on the radioallergosorbent technique.

Cat allergen-specific serum IgE antibodies were detected in 27 (71%) of a group of 38 dog dander-sensitive patients. In 4 (44%) of the cases the dual reaction could be explained by the presence of IgE antibodies to cross-reacting serum proteins. In a larger group the binding of dog dander-specific IgE antibodies could be inhibited by cat epithelium allergens. Two allergenic components of dog dander were separated by chromatography on Sephadex G-75. One of the allergens was closely related to a purified major cat epithelium allergen. The other allergen was apparently dog-specific and showed no cross-reactivity with cat allergens. Both components were present in the dander of dachshund, Airedale terrier, poodle and boxer. The dog dander is the preferable source of dog epithelium allergens provided that the existence of relations to other animals is considered.

Allergens↗

[The diagnostic significance of microcalcifications in testicular tumors (author's transl)].

The evaluation of total orchiectomy tissue specimens with malignant testicular tumors shows that microcalcifications can be found in a surprisingly high percentage by radiological and histological examinations. Small, often in several groups located calcifications in the parenchyma neighbouring the tumor are typical for seminoma, whereas in teratoma solitary microcalcifications and polymorphic types can also be seen. Microcalcifications are also present in not neoplastic testicular diseases but in a much smaller percentage and with a different type of calcification. The preoperative radiographic examination of testicular tumors of unknown origin seems to be indicated as a non-invasive method able to provide further information about the presence of a malignant germ cell tumor. Regarding the genetic risks of the method, there is hope to avoid other more invasive examinations with their danger of tumor spreading and to enable a radical resection of the primary tumor before its metastic formation by the mean of preoperative orchioradiography.

Calcinosis↗