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Biomedical subjects

U Quast

Publications and source records attributed to U Quast.

At least 91 records · Page 5Linked to original sources
PubMed1990

Late effects of total body irradiation in correlation with physical parameters.

Clear and complete documentation of the physical parameters of total body irradiation (TBI) is one of the essential requirements for the evaluation and improvement of the clinical results of TBI. Concerning the dosimetric aspects of TBI, a number of recommendations have been formulated with emphasis on basic dosimetry, patient dosimetry and dose specification. The dosimeters should be calibrated regularly with reference to the absorbed dose in water. Depth dose measurements should be performed in water equivalent phantoms of specified dimensions. It has been strongly suggested to measure the absorbed dose at the surface of the patient at 8 different regions at the entry and exit of the beam under TBI conditions. The reference dose to the patient should be specified as the total dose to mid abdomen at the height of the umbilicus. As an independent parameter, the lung dose should be specified as the mean dose in the central region of the shielded part of both lungs. Recent, more complete, information on the physical and dosimetric aspects of TBI will be incorporated in the registry of the European Bone Marrow Transplant Group (EBMT). A cooperation has been established between the EBMT and the European Late Effects Project Group (EULEP) to study the development of late effects in man caused by ionising radiation.

Calibration↗
PubMed1990

Measles-mumps vaccination in the FRG: an empirical analysis after 14 years of use. I. Efficacy and analysis of vaccine failures.

One hundred and ninety two reports on vaccine failures after measles and mumps vaccination are analysed. These reports were received by the Drug Surveillance Department at Behringwerke between 1976 and 1989. Seventy-six per cent of the suspected measles and 41% of the suspected mumps cases occurred within the first 3 years postvaccination. Most probably these were primary vaccine failures. The analysis of the data collected in the 14 years since the introduction of measles-mumps vaccination in the FRG gives no reason to suspect that the protection afforded by the vaccines wanes with time.

Child↗
PubMed1990

Measles-mumps vaccination in the FRG: an empirical analysis after 14 years of use. II. Tolerability and analysis of spontaneously reported side effects.

Four hundred and thirty-three reports of suspected side effects following measles-mumps vaccination had been received at Behringwerke by the end of December 1989. The analysis of the data shows that no new risks of the vaccination could be identified and that the frequency of side effects is in good agreement with the findings of other authors. It therefore can be assumed that the relative risks of the vaccination continue to be distinctly outweighed by the benefits. The findings clearly demonstrate once more that it is necessary to carry out a thorough differential diagnosis before one can assume that the symptoms observed are causally related to the vaccination. In addition the analysis shows the importance of the epidemiological approach to the assessment of rare side effects.

Adult↗
PubMed1989

In vitro and in vivo comparison of two K+ channel openers, diazoxide and cromakalim, and their inhibition by glibenclamide.

Diazoxide caused an increase in 86Rb+ efflux from the rat aorta and portal vein and inhibited spontaneous activity of the latter at concentrations 100 times higher than the K+ channel opener cromakalim. In the rabbit aorta both drugs inhibited vasoconstrictor responses to angiotensin II, noradrenaline and low concentrations (less than or equal to 30 mM) of KCl in a similar manner, the antivasoconstrictor activities being abolished in vessels depolarized with greater than or equal to 35 mM K+. In vivo cromakalim was about 100 times more potent than diazoxide at lowering blood pressure in rats. Diazoxide (30 mg/kg) caused a more than 2-fold increase in plasma glucose in rats and prevented any return toward base line within 1.5 hr after a glucose load. Cromakalim had minimal effects upon glucose homeostasis at equihypotensive doses. Glibenclamide, a potent blocker of ATP-dependent K+ channels, inhibited the stimulation by cromakalim and diazoxide of 86Rb+ efflux from the portal vein and aorta (IC50 approximately 0.1 microM), antagonized their vasorelaxant effects in vitro and in vivo (20-30 mg/kg i.v.) and reversed the diazoxide-induced changes in plasma glucose and insulin levels. These results provide evidence that diazoxide, like cromakalim, is able to open 86Rb+-permeable K+ channels in vascular smooth muscle. This action is likely to be responsible for the in vitro and in vivo vasodilator activity of these two drugs. However, there would seem to be pharmacological differences between the K+ channels affected by these drugs in vascular smooth muscle and the (ATP-sensitive) K+ channels of pancreatic beta-cells, which are thought to be responsible for the effects of diazoxide on plasma glucose.

Angiotensin II↗
PubMed1988

Pertussis toxin treatment does not inhibit the effects of the potassium channel opener BRL 34915 on rat isolated vascular and cardiac tissues.

The experiments were undertaken to determine whether the effects of the K+ channel opener BRL 34915 on rat isolated vascular smooth muscle and atria were sensitive to pertussis toxin (PTx). PTx treatment of rats (100 micrograms/kg, infused over 15 min) affected some baseline parameters of the isolated tissues: in the atria, heart rate was increased, contractile force was decreased and the basal efflux of 86Rb+ was increased; in portal veins, the spontaneous activity was decreased but the contractility of aortic rings was unaffected. In the isolated atria removed from saline-treated rats, carbamylcholine decreased heart rate and contractile force, shortened the action potential duration by increasing the maximum rate of repolarization and increased 86Rb+ efflux. These effects of carbamylcholine were completely abolished in the atria from PTx-treated rats, demonstrating the efficacy of the toxin. The ability of 300 microM BRL 34915 and of 55 mM KCl to increase atrial 86Rb+ permeability was, however, only slightly affected by PTx treatment. In portal veins from PTx-treated rats, the efficacy of BRL 34915 to inhibit spontaneous activity and to increase 86Rb+ efflux was the same as in control organs. Similarly, in aortic rings, the ability of BRL 34915 to inhibit contractions to low concentrations of KCl or to noradrenaline was unaffected by PTx treatment as was the 86Rb+ efflux response to BRL 34915 in this tissue. It is concluded that PTx treatment does not inhibit the effects of BRL 34915 in the tissues investigated. The results are compatible with the notion that BRL 34915 does not open K+ channels by acting through a PTx-sensitive G-protein.

Action Potentials↗
PubMed1988

Comparison of the effluxes of 42K+ and 86Rb+ elicited by cromakalim (BRL 34915) in tonic and phasic vascular tissue.

The cromakalim-induced effluxes of 42K+ and 86Rb+ were compared in rat aortic segments and in guinea-pig portal vein. In both vessels, low concentrations of cromakalim (0.1 microM) increased the permeability to 86Rb+ 3-4 times less than that to 42K+; at 10 microM the difference was about a factor of 1.3-2. In rat aorta, the threshold concentration of cromakalim for 42K+ efflux was greater than or equal to 0.03 microM; with 86Rb+ as the tracer ion it was 0.1 microM. At similar concentrations, cromakalim relaxed the tension of aortic segments precontracted with 23 mM KCl (IC50 = 0.06 +/- 0.01 microM). However, no concomitant increase in 42K+ or 86Rb+ efflux could be detected from this stimulated preparation at these concentrations. In guinea-pig portal vein, 42K+ efflux measurements were performed in the presence and absence of the dihydropyridine Ca2+ entry blocker PN 200-110 (isradipine) yielding comparable results. In the presence of PN 200-110, where spontaneous activity and the K+ efflux associated with it were abolished, the threshold concentration of cromakalim for 42K+ efflux was 0.02 microM as compared to 0.06 microM for 86Rb+ efflux. In the absence of PN 200-110, spontaneous activity of the portal vein was inhibited by 70% and 90% at these concentrations. In double isotope experiments, the K+ channel inhibitor tetraethylammonium did not discriminate between the effluxes of 42K+ and 86Rb+ stimulated by cromakalim. It is concluded that in the two vascular tissues examined, cromakalim increased the permeability to 42K+ more than to 86Rb+, the difference being more marked at low cromakalim concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Leiurus quinquestriatus venom inhibits BRL 34915-induced 86Rb+ efflux from the rat portal vein.

The effect of the crude venom of the Israeli scorpion Leiurus quinquestriatus hebraeus on the 86Rb+ efflux stimulated by the K+ channel opener BRL 34915 in the rat portal vein was examined. Applied alone, the venom greatly increased the spontaneous mechanical activity of and the concomitant 86Rb+ efflux from the vessel. When the excitability of the vein was suppressed by the dihydropyridine calcium antagonist, PN 200-110, the 86Rb+ efflux stimulated by BRL 34915 could be shown to be inhibited by the venom. From the concentration dependence of this inhibition an IC50 value of 0.17 +/- 0.01 mg/ml was estimated. This venom is thus the most potent blocker of BRL 34915-evoked 86Rb+ efflux reported so far.

Animals↗
PubMed1988

Similarities in the mechanism of action of two new vasodilator drugs: pinacidil and BRL 34915.

The present study compares the in vitro and in vivo activities of pinacidil with another new vasodilator drug, BRL 34915, claimed to act via the opening of K+ channels in vascular smooth muscle. In the rabbit aorta, BRL 34915 and pinacidil caused rightward shifts of the KCl concentration-response curve and noncompetitively antagonized angiotensin II contractions, yielding an IC50 of 5 and 10 microM, respectively. In 86Rb-loaded guinea pig portal veins, both BRL 34915 and pinacidil stimulated 86Rb+ efflux over the concentration range 0.3-30 microM. At saturating concentrations, the maximum efflux elicited by pinacidil was only one-third that of BRL 34915. Spontaneous activity measured simultaneously from the same vessels was inhibited by BRL 34915 and pinacidil with an IC50 of 12 and 32 nM, respectively. Effects on mechanical activity were thus observed at drug concentrations 100-fold lower than those required to stimulate 86Rb+ efflux. In anesthetized rats, both compounds rapidly lowered blood pressure, with BRL 34915 being threefold more potent than pinacidil in this respect. Tachycardia was more pronounced after BRL 34915 than after pinacidil. Angiotensin II pressor responses were poorly antagonized by these two vasodilators in rats, in marked contrast to the potent effects of Ca2+ antagonists on these responses at equieffective hypotensive doses. We conclude the pinacidil, like BRL 34915, is a potent antihypertensive that is able to enhance the K+ permeability of vascular smooth muscle. The similarities between these two drugs suggest they have a common mechanism of action. However, the discrepancy between the concentrations of these drugs necessary to stimulate 86Rb efflux, and those at which mechanical effects are seen in the portal vein, do not rule out the possibility that other actions may contribute to their vasodilator activities.

Animals↗
PubMed1988

Mechanism of action and systemic and regional hemodynamics of the potassium channel activator BRL34915 and its enantiomers.

BRL34915 (BRL) is a vasodilator with a novel structure. Its mechanism of action, its effects on depolarization-induced and receptor-mediated blood vessel contraction, and its hemodynamic effects were investigated. In the rat portal vein, BRL inhibited spontaneous mechanical activity [IC50 0.013 +/- 0.001 microM (mean +/- SEM) for (-)-BRL], the initial effect being a reduced frequency of contraction. At higher concentrations, the spontaneous contractions were abolished and 86Rb+ efflux was increased. These results suggest that BRL preferentially acts on the pacemaker cells, the K+ channels in other cells being activated only at higher BRL concentrations in this vessel. In experiments on the rabbit aorta, (-)-BRL shifted the KCl concentration-response curve to the right and noncompetitively inhibited responses to angiotensin II. A concentration of 3 microM (-)-BRL reduced maximal angiotensin II contractions by around 50%, higher concentrations having little further effect. This inhibition of angiotensin II contractions is notably greater than that seen with Ca2+ antagonists in this vessel. In anesthetized rabbits, (-)-BRL was a peripheral vasodilator at doses of 3-30 micrograms/kg, but it had no relevant effects on heart rate and myocardial contractile force. This suggests tissue selectivity of this compound or this mechanism of action. BRL preferentially dilated the coronary, gastrointestinal, and cerebral vessels but not those of the kidneys or skeletal muscle as measured with tracer microspheres. This profile of activity is different from that of calcium antagonists or nonspecific vasodilators like dihydralazine. All effects were stereoselective, the (-)-enantiomer being 100 to 200 times more active than the (+)-enantiomer.

Animals↗
PubMed1987

Bone marrow transplantation in acute leukemia.

In Essen 142 bone marrow transplantations were carried out between December 1975 and February 1985. In 74 cases the indication was acute leukemia in relapse (n = 23) or in first or consecutive remission (n = 51). The conditioning regimen consisted of cyclophosphamide or the combination of cyclophosphamide and total body irradiation. All patients were treated under strict gnotobiotic care. To mitigate the risk of CMV infections, intravenous CMV-hyperimmune globulin and CMV-negative blood products have been applied routinely for 2 years. MTX was used as prophylaxis against GvHD. In the prognostically unfavorable group of acute leukemia in relapse, only one patient showed long-term survival. In this patient, leukemic relapse occurred 6 years after transplantation. The survival rate of AML patients grafted during the first remission is 55% (16/29) with a median observation time of 41 months. For patients grafted in first or consecutive remission of acute lymphoblastic leukemia, the survival rate is 50% (7/14) with a maximal observation time of 34 months. The overall incidence of GvHD in patients at risk was 28% in aplastic anemia, 26% in AML, 9% in ALL, and 63% in CML. In aplastic anemia, no patient developed an interstitial pneumonia. In leukemia, the risk of fatal interstitial pneumonia was 34%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Allogeneic bone marrow transplantation for acute leukaemia or chronic myeloid leukaemia in the fifth decade of life.

To determine the influence of advanced age on long-term survival after allogeneic bone marrow transplantation (BMT), the probability of survival and the frequency of transplantation-associated complications were analysed retrospectively in 20 patients with acute leukaemia (AL) or chronic myeloid leukaemia (CML), who were 40-49 years of age (median 44.5 years) at the time of transplant. The results of this patient group were compared to those of 32 patients aged 30-39 years (median 33.5 years) with AL or CML, who also underwent BMT during the same period of time. The overall actuarial survival of the two age groups was comparable with 44% and 41% at 5.9 and 5.6 years, respectively. Patients with standard risk criteria (i.e. HLA-genotypically identical sibling donor, 1st chronic phase of CML or 1st remission of AL) showed a higher probability of survival in both groups (62% at 5.9 years in older patients and 59% at 5.5 years in younger patients, respectively). In contrast, actuarial survival in patients who underwent BMT at an advanced stage of their disease or with marrow from a partially HLA-compatible donor was significantly inferior (P = 0.04). The cumulative incidence of acute and chronic graft-versus-host disease was low in older patients (27%), who received marrow from an HLA-identical sibling donor. The most frequent cause of death was interstitial pneumonia, occurring in seven of the older patients (35%) and in seven of the younger patients (22%). This difference, however, was not statistically significant. Our results indicate that allogenic marrow transplantation in the fifth decade of life might be associated with a tolerable risk of transplantation-related complications. This treatment modality may therefore be regarded as first-line therapy for patients in 1st remission of AL or first chronic phase of CML, who show a normal performance status. The same applies to older patients in advanced stages of disease, since the results are comparable to those achieved in the younger patient group.

Acute Disease↗
PubMed1987

Total body irradiation--review of treatment techniques in Europe.

In treatment of acute leukaemia and other disseminated diseases, high dose total body irradiation (TBI) combined with intensive chemotherapy and bone marrow transplantation (BMT) is used more and more successfully. Reflecting the complex clinical, biological, physical and technical situation of TBI, a large variety of TBI treatment techniques has been developed. In order to review the techniques applied in Europe and to report about common methods as well as about new ideas in TBI, a questionnaire was prepared and mailed to medical physicists in Europe responsible for TBI. The topics of this questionnaire are general information: TBI technique (beams, fields, treatment conditions); basic TBI dosimetry; physical treatment planning (patient dosimetry, heterogeneity correction, dose modification, dose homogeneity, dose precision, confirmation measurements); TBI treatment planning (dose prescription, localization, documentation, verification, in vivo dosimetry); requirements (additional staff, time, equipment) and recommendations for improvement of TBI. Most questionnaires (34/45) were returned in time with detailed information from TBI centres in 15 European countries. These data as well as results of the "Meeting of Leiden, 1982" of the "Meeting of Essen, 1985" and of the "Meeting of Toulouse, 1986" are summarized and discussed. There are many interesting methods to plan and perform exact TBI. However, anterior-posterior TBI is preferred to achieve sufficient homogeneity of dose and effective lung shielding. While the development of TBI has reached a high level of exactness, further improvement will require a better knowledge of the dose-effect relationships.

Acute Disease↗
PubMed1987

Na+ channels as sites of action of the cardioactive agent DPI 201-106 with agonist and antagonist enantiomers.

This paper shows the interaction of the cardiotonic agent 4-[3-(4-diphenylmethyl-1-piperazinyl)-2-hydroxypropoxy]-1H-indole- 2-carbonitrile (DPI 201-106) and its optic enantiomers R-DPI (205-429) and S-DPI (205-430) with the Na+ channel of a variety of excitable cells. Voltage-clamp experiments show that DPI 201-106 acts on neuroblastoma cells and rat cardiac cells. S-DPI (205-430) increases the peak Na+ current, slows down the kinetics of Na+ channel inactivation, and is cardiotonic on heart cells. Conversely, R-DPI (205-429) reduces the peak Na+ current and blocks Na+ channel activity and cardiac contractions. Binding experiments using radioactively labeled toxins indicate that DPI 201-106 and its enantiomers do not interact with sites already identified for tetrodotoxin or sea anemone and scorpion toxins. DPI 201-106 and its enantiomers inhibit binding of a 3H-labeled batrachotoxin derivative, [3H]batrachotoxinin A 20-alpha-benzoate, to brain membranes. The dissociation constant of the complex formed between the Na+ channel and both R-DPI and S-DPI is Kd congruent to 100 nM. 22Na+ uptake experiments using different cell types have shown that R and S enantiomers of DPI 201-106 are active on the different Na+ channel subtypes with similar IC50 values. These results are discussed in relation with the cardiotonic properties of DPI 201-106 that are not accompanied by cardiotoxic effects.

Animals↗