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  • 1
    Electronic Resource
    Electronic Resource
    THE PURPOSE OF THIS MONOGRAPH (1960)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 86 (1960), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1960.tb42785.x
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  • 2
    Electronic Resource
    Electronic Resource
    Structures of the Major Metabolites of Meprobamate (1960)
    s.l. : American Chemical Society
    Journal of medicinal chemistry 3 (1960), S. 53-64 
    Details
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jm50014a004
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  • 3
    Electronic Resource
    Electronic Resource
    Androgen-Regulated Gene Expression (1989)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 51 (1989), S. 51-65 
    Details
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.ph.51.030189.000411
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  • 4
    Electronic Resource
    Electronic Resource
    Primary pulmonary non-Hodgkin's lymphomas (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Histopathology 26 (1995), S. 0 
    Details
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We report a retrospective study of the pathological features in 69 primary pulmonary non-Hodgkin's lymphomas which have previously been clinically reviewed. The tumours consisted of 61 (88%) low-grade and eight (12%) high-grade malignant lymphomas. Fifty-four of the low-grade malignant lymphomas were MALT lymphomas. Lymphoepithelial lesions were observed in bronchial, bronchiolar and alveolar lining. All tumours were composed of nodules, forming a lymphangitic pattern at the periphery and a confluent central mass. Invasion of pleura and vessels was often seen but this without any consequence on survival. Granulomas were found in 20% of cases. Six of the eight high-grade tumours were centroblastic and another two were B-cell lymphomas of undetermined type. In four cases, associated areas of low-grade malignant lymphoma with lympho-epithelial lesions indicated a preexisting MALT lymphoma. Clinical data suggest that limited surgery or non-aggressive chemotherapy can provide long-term survival in patients with such slowly developing neoplasms. However, non-invasive diagnostic methods need to be developed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2559.1995.tb00271.x
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  • 5
    Electronic Resource
    Electronic Resource
    Inhibition of pacemaker current by the bradycardic agent ZD 7288 is lost use-dependently in sheep cardiac Purkinje fibres (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1995), S. 64-72 
    Details
    ISSN: 1432-1912
    Keywords: Sheep cardiac Purkinje fibre ; Voltage-clamp ; Pacemaker current ; Use dependence ; Specific bradycardic agent ; ZD 7288
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The inhibition of the pacemaker current (i f) in sheep cardiac Purkinje fibres by ZD 7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium chloride] is lost use-dependently. This disinhibition of i f was investigated by using the two-microelectrode voltage-clamp technique. The pulse protocol consisted of a rest period (holding potential of about -50 mV, 1–10 μmol/l ZD 7288) followed by a train of test pulses (potential negative to -100 mV, stimulation frequency 0.05 Hz). At the beginning of the first test pulse there was an immediate reduction of i f but inhibition was lost during continued stimulation. Activation of i f is sigmoidal and the early delay in current activation was prolonged from 33 ms (no ZD 7288) to 424 ms (10 μmol/l ZD 7288). Therefore hardly any disinhibition occurred during short test pulses (0.5 s). During longer test pulses (5 s, -120 mV, 10 μmol/l) disinhibition developed with a time constant of about 2 s. The inhibition of i f by ZD 7288 was lost voltage-dependently. With 10 μmol/l ZD 7288 the half-maximal disinhibition occurred at -92 mV and the slope factor of the disinhibition/voltage curve (Boltzmann relation) was 4.8 mV. The voltage-dependent disinhibition could be abolished largely by extracellular application of protease (0.5 mg/ml, 7 min). After prior disinhibition, reinhibition at the holding potential (about -50 mV) followed a bi-exponential time course indicating that inhibition may be produced by a fast (τ=0.7 min) and a slow component (τ=20–30 min). Increasing ZD 7288 concentration from 1 to 10 μmol/l accelerated reinhibition, mainly by an increase of the amplitude (A) of the fast component. The ratio A fast/A sIow was 0.399 at 1 μmol/l and 2.65 at 10 μmol/1 ZD 7288. The reinhibition of i f was unchanged by shifting the holding potential from -50 mV to -20 mV Trials to wash out the effects of 10 μmol/l ZD 7288 gave two results. The inhibition of i f was slightly reversed after a wash-out of 1.5 h with drug-free solution. A second effect of the drug, the fast reinhibition, could be completely removed by washout. In summary i f is inhibited by ZD 7288 at membrane potentials at which the virtual i f gate is closed. Disinhibition occurs during long-lasting hyperpolarization but will hardly be operative in unclamped fibres under physiological conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168917
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  • 6
    Electronic Resource
    Electronic Resource
    Inhibition of pacemaker current by the bradycardic agent ZD 7288 is lost use-dependently in sheep cardiac Purkinje fibres (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1995), S. 64-72 
    Details
    ISSN: 1432-1912
    Keywords: Key words Sheep cardiac Purkinje fibre ; Voltage-clamp ; Pacemaker current ; Use dependence ; Specific bradycardic agent ; ZD 7288
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The inhibition of the pacemaker current (i f) in sheep cardiac Purkinje fibres by ZD 7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium chloride] is lost use-dependently. This disinhibition of i f was investigated by using the two-microelectrode voltage-clamp technique. The pulse protocol consisted of a rest period (holding potential of about –50 mV, 1–10 μmol/l ZD 7288) followed by a train of test pulses (potential negative to –100 mV, stimulation frequency 0.05 Hz). At the beginning of the first test pulse there was an immediate reduction of i f but inhibition was lost during continued stimulation. Activation of i f is sigmoidal and the early delay in current activation was prolonged from 33 ms (no ZD 7288) to 424 ms (10 μmol/l ZD 7288). Therefore hardly any disinhibition occurred during short test pulses (0.5 s). During longer test pulses (5 s, –120 mV, 10 μmol/l) disinhibition developed with a time constant of about 2 s. The inhibition of i f by ZD 7288 was lost voltage-dependently. With 10 μmol/l ZD 7288 the half-maximal disinhibition occurred at –92 mV and the slope factor of the disinhibition/voltage curve (Boltzmann relation) was 4.8 mV. The voltage-dependent disinhibition could be abolished largely by extracellular application of protease (0.5 mg/ml, 7 min). After prior disinhibition, reinhibition at the holding potential (about –50 mV) followed a bi-exponential time course indicating that inhibition may be produced by a fast (τ=0.7 min) and a slow component (τ=20–30 min). Increasing ZD 7288 concentration from 1 to 10 μmol/l accelerated reinhibition, mainly by an increase of the amplitude (A) of the fast component. The ratio A fast/A slow was 0.399 at 1 μmol/l and 2.65 at 10 μmol/l ZD 7288. The reinhibition of i f was unchanged by shifting the holding potential from –50 mV to –20 mV. Trials to wash out the effects of 10 μmol/l ZD 7288 gave two results. The inhibition of i f was slightly reversed after a wash-out of 1.5 h with drug-free solution. A second effect of the drug, the fast reinhibition, could be completely removed by wash-out. In summary i f is inhibited by ZD 7288 at membrane potentials at which the virtual i f gate is closed. Disinhibition occurs during long-lasting hyperpolarization but will hardly be operative in unclamped fibres under physiological conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168917
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  • 7
    Electronic Resource
    Electronic Resource
    Effects of (+)- and (±)-sotalol on repolarizing outward currents and pacemaker current in sheep cardiac Purkinje fibres (1989)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 696-704 
    Details
    ISSN: 1432-1912
    Keywords: Sheep Purkinje fibre ; Outward currents ; Pacemaker current ; (+)-Sotalol ; (±)-Sotalol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study was aimed to differentiate the action of (+)- and (±)-sotalol (10–1000 μmol/l) on membrane currents which are active during the repolarization of cardiac action potentials Effects where studied in shortened sheep cardiac Purkinje fibres with the two-microelectrode voltage-clamp technique Action potentials were activated at a frequency of 0.25 Hz and membrane currents at 0.03 Hz or 0.05 Hz in most experiments. Out of the currents investigated the transient outward current (ito) reacted most sensitively to (+)- and (±)-sotalol. Ito-amplitude was decreased on the average to 77% of reference at 10 μmol/l and to 53% at 1000 μmol/l (+)- or (±)-sotalol. The maximally available ito-current was decreased but the voltage-dependent control of inactivation was left nearly unchanged. The initial inwardly rectifying current (iKi), which propels the last repolarization phase of the action potential and controls resting potential to a large extent was reduced on the average to 93% of reference at 10 μmol/l and to 62% at 1000 μmol/l (+)- or (±)-sotalol. Time-dependent (delayed) outward current (iK) was on the average not affected by (+)- or (±)-sotalol up to 100 μmol/l and was decreased to 84% of reference current under the influence of 1000 μmol/l. An initial outward current, which is activated at positive membrane potentials (iinst) was not clearly affected by (+)- or (±)-sotalol at concentrations up to 1000 μmol/l Pacemaker current (if) was not influenced by the drugs up to 100 μmol/l. Only at 1000 μmol/l was the amount of available if-current decreased to 79% of reference. (The potential-dependent control of activation was not affected) Time constants of time-dependent currents ito, iK and if did not change in concentrations up to 1000 μmol/l of the drug. Action potential duration increased at (+)- or (±)-sotalol concentrations ≥ 10 μmol/l and maximal prolongation was achieved at concentrations of 100–300 μmol/l Resting potential remained nearly unchanged at these concentrations, but the membranes depolarized at 1000 μmol/l. According to our data action potential prolongation in sheep Purkinje fibres under the influence of (+)- and (±)-sotalol correlates to the drug-induced block to ito-current and inwardly rectifying iK1-current.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00717747
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  • 8
    Electronic Resource
    Electronic Resource
    Effects of the calcium entry blocker bepridil on repolarizing and pacemaker currents in sheep cardiac Purkinje fibres (1989)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 638-646 
    Details
    ISSN: 1432-1912
    Keywords: Sheep Purkinje fibre ; Voltage clamp ; Ionic outward currents ; Calcium entry blocker ; Bepridil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary (1) Effects of bepridil (0.3–100 μmol/l) on transmembrane currents which are active during the repolarization of the cardiac action potential were studied in sheep cardiac Purkinje fibres with the two-microelectrode voltage-clamp technique. Transmembrane currents were activated at a frequency of 0.03 Hz. (2) The initial inwardly rectifying current (i K1) was reduced by 1.8 μmol/l bepridil to 70% of the reference i K1-current in the absence of the drug. (3) An initial outward current, which is activated at positive membrane potentials (i inst) was depressed to 70% of reference by 14 μmol/l bepridil. (4) The time-dependent outward current (i K) was decreased by 1.8 μmol/l bepridil to 70% of its amplitude in the absence of bepridil. The biexponential time course of i K-current activation changed to be monoexponential with 100 μmol/l bepridil. The effect of bepridil on i K-current resulted in a shift of the activation curve of i K-current to more positive membrane potentials (10 μmol/l bepridil) and an additional decrease of driving force and/or conductance of the i K-channels with higher bepridil concentrations (100 μmol/l). (5) The transient outward current (i to) was completely blocked by 30 μmol/l bepridil. Inhibition to 70% of reference occurred with 1 μmol/l bepridil. The voltage-dependent inactivation of i to-current was affected by bepridil: the amplitude of the steady-state inactivation curve was reduced and i to-current was inactivated faster after application of bepridil. Bepridil caused no pronounced shift of the steady-state inactivation curve along the voltage axis. (6) The pacemaker current (i f) was slightly increased under the influence of low bepridil concentrations (0.3, 1 μmol/l) while it was reduced to 70% of reference by 100 μmol/l bepridil. (7) The blocking action of bepridil on outward currents in sheep cardiac Purkinje fibres will explain the action potential prolongation, which is observed in different mammalian cardiac tissues under the influence of bepridil.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168656
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  • 9
    Electronic Resource
    Electronic Resource
    „Duktusspiel”Lösbares Problem für den katheterinterventionellen Verschluß (1997)
    Springer
    Monatsschrift Kinderheilkunde 145 (1997), S. 798-801 
    Details
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Persistierender Ductus arteriosus (PDA) ; Katheterinterventioneller PDA-Verschluß ; Raskind-occluder ; Key words Patent ductus arteriosus (PDA) ; Transcatheter closure of PDA ; Rashkind occluder ; Front-loading-technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Transcatheter closure of patent ductus arteriosus Botalli (PDA) has become a routine procedure. Only PDA in low birth weight infants, and short and wide open PDA in small children could not be closed by means of catheter technology. Different transcatheter closure systems are available now. We report on a premature infant now 16 month old weighting 6,8 kg were surgery seemed inadvisable. After angiography a funnel- shaped PDA seemed to be suitable for closure by a Ductocclud spiral coil (PFM company). The spiral coil could not be set in place safely because meanwhile the pulmonary PDA month had widened after angiography. Transcatheter closure then was successful using a 17 mm Rashkind double umbrella (Bard company) in modified implantation technique with a 8 french introduction set, and special attention to avoid the isthmus of the aorta and pulmonary artery stenosis. Discussion: Ductal reactivity at an age of 16 months seems unusual. Even at this age one has to be aware of possibly dramatic changes of the shape of the ductus during examination. Experience with several transcatheter PDA-closure systems is necessary for the successful closure even in cases of unexpected changes of shape of PDA.
    Notes: Zusammenfassung Der katheterinterventionelle Verschluß eines persistierenden Ductus arteriosus Botalli (PDA) ist heute eine Routinemethode, für die eine ganze Reihe von verschiedenen Verschlußsystemen zur Verfügung steht. Eine Ausnahme für die Intervention stellen nur noch Frühgeborene und kleine Kinder mit kurzen, weit offenen Duktus dar. Wir berichten über ein 16 Monate altes, 6,8 kg schweres ehemaliges Frühgeborenes mit relativen Kontraindikationen zu einer Operation, bei dem nach Angiographie ein trichterförmiger Duktus zum Verschluß durch eine Ductocclud-Spirale (Fa. PFM) geeignet erschien. Die Spirale war jedoch nicht sicher zu plazieren, da sich die pulmonale Duktusmündung durch die mit der Intervention verbundenen Manipulationen zwischenzeitlich erheblich geweitet hatte. Der Verschluß des PDA gelang dann mit einem 17-mm-Rashkind-Doppelschirm (Fa. Bard) in modifizierter Implantationstechnik mit einer 8-Fr.-Schleuse unter besonderer Berücksichtigung der Schonung der Aortenisthmusregion und der Pulmonalarterienstrombahn. Diskussion: Die Empfindlichkeit des Duktusgewebes noch im Alter von 16 Monaten erscheint ungewöhnlich. Der Untersucher muß auch in diesem Alter auf drastische Änderungen der Duktusmorphologie vorbereitet sein. Bei entsprechender Erfahrung mit verschiedenen Verschlußsystemen kann die Intervention trotz „Duktusspiel” gelingen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001120050179
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  • 10
    Electronic Resource
    Electronic Resource
    H1-receptor reserves in guinea-pig left atria, trachea and pig coronary artery as identified by phenoxybenzamine (1989)
    Springer
    Inflammation research 28 (1989), S. 218-223 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract H1-receptor reserves in guinea-pig left atria, trachea and pig coronary arteries were calculated by the use of phenoxybenzamine (Pba), a β-haloalkylamine that irreversibly blocks the H1-receptor response to histamine or 2-(2-pyridyl)-ethylamine (PEA). Equieffective concentrations of the H1-agonist in the absence (A) and presence (A′) of Pba were evaluated from concentration-response curves. By plotting the reciprocal values 1/A versus 1/A′ the amount of H1-receptors not occupied by the agonist was calculated. The size of the H1-receptor reserve could be estimated by comparison of the receptor occupation with the corresponding effect. Furthermore, the dissociation constants for histamine, PEA, Pba and the pD′2-values for Pba were determined for the different tissues. 5% and 6% H1-receptor occupation is necessary to achieve a half maximal contraction of the trachea with the agonists histamine and PEA, respectively. Only 0.5% H1-receptor occupation is needed for the half maximal positiv inotropic effect of histamine in left atria, while 5.5% of the H1-receptors have to be accupied using PEA as an agonist in this tissue. In the coronary artery of the pig 50% of the maximal contraction can be achieved by stimulation of 15.1% of the H1-receptors with histamine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01967405
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