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  • 1
    ISSN: 1432-1041
    Keywords: isosorbide 5-mononitrate ; angina pectoris ; asymmetrical dosage timing ; tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Isosorbide 5-mononitrate is an active metabolite of isosorbide dinitrate and possesses many theoretical advantages over its parent drug. However, the development of partial tolerance has been demonstrated when the drug is given 12 hourly or 8 hourly. We have therefore evaluated the acute and sustained (2 weeks) effects of isosorbide-5-mononitrate 40 mg given twice daily (08.00 h and 14.00 h, allowing an 18-h dose-free period) in 19 patients with stable chronic angina, using computerized exercise testing and a placebo-controlled, double-blind, randomized trial protocol. There were two phases of 2 weeks each in which patients received placebo or active isosorbide-5-mononitrate. Acute testing was performed 2 h after the first dose and chronic testing 2 h after the morning dose on Day 14. Acute testing showed an increase in exercise time from a mean (SD) of 6.7 (2.2) min to 10.1 (2.95) min (P〈0.01) after a single dose of isosorbide-5-mononitrate 40 mg. The time to 1 mm of ST depression, and rest and peak exercise heart rates increased significantly during acute testing with isosorbide-5-mononitrate; resting and peak exercise systolic blood pressures fell significantly. Due to drop outs cross-over analysis was performed on 11 patients who completed both chronic phases and 13 patients were assessed for the comparison of acute isosorbide-5-mononitrate with chronic isosorbide-5-mononitrate. After 2 weeks of therapy exercise time did not show a sustained increase 8.01 (2.14) min chronic placebo to 8.58 (1.93) min chronic isosorbide-5-mononitrate. The improvement in ST segment variables seen acutely was not sustained. These data suggest that the attenuation of the effect of isosorbide-5-mononitrate due to partial tolerance is not mitigated by using an asymmetrical dose regimen.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 37 (1989), S. 551-554 
    ISSN: 1432-1041
    Keywords: nisoldipine ; hypertension ; ambulatory monitoring ; cuff blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cuff blood pressure data has suggested that the calcium channel antagonist nisoldipine has full twenty four hour efficacy. To test this, 24 h ambulatory intra-arterial blood pressure monitoring was performed on 18 untreated hypertensive subjects (12 men, 6 women) (cuff blood pressure 〉150/95 mm Hg) before and after chronic treatment with 10–20 mg oral nisoldipine taken daily at 08.00 h. Twelve patients completed the study, six being withdrawn, four because of side-effects. After baseline intra-arterial monitoring patients were started on 10 mg nisoldipine daily. Response was assessed by cuff pressures taken 24 h after dosing at fortnightly intervals, and if not controlled (〈150/95 or at least 10 mm Hg reduction in diastolic BP) the dose was increased to 20 mg. All patients received at least six weeks' therapy before the second intra-arterial blood pressure monitoring. There was a slight but insignificant reduction in mean daytime heart rate of 3 beats·min−1. Mean significant reduction in daytime systolic and diastolic BP was 19 mm Hg and 13 mm Hg respectively but there was no significant mean night-time reduction. By comparison 8 out of 12 patients were apparently controlled more than 24 h post dose according to cuff pressures. This study suggests that this formulation of nisoldipine does not control blood pressure over a full 24-h period, and emphasises the importance of 24 h ambulatory monitoring in assessing the efficacy of once-daily antihypertensive agents.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Diltiazem ; Hypertension ; intra-arterial blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The aim of the study was to examine the efficacy of a new controlled release formulation of diltiazem administered in a twice-daily dose in patients with essential hypertension using 24 hour intra-arterial ambulatory blood pressure monitoring. Sixteen patients (2 female) of mean age 53 years with mild to moderate essential hypertension, defined as a supine resting diastolic cuff blood pressure ≥95 mm Hg, were recruited to a sequential dose ranging study of controlled release (CR) diltiazem. After a six week run-in period without any anti-hypertensive medication, intra-arterial blood pressure monitoring with 60° tilt, isometric handgrip and bicycle exercise testing were performed. Patients were then treated for one week with CR diltiazem 120 mg b.i.d. If supine resting diastolic cuff blood pressure fell by 〈10 mm Hg compared to the last run-in value and remained 〉90 mm Hg, the dose was increased to 240 mg b.i.d. for a week, and if necessary to 360 mg b.i.d. for a week. Patients continued for further one month on the dose of CR diltiazem at which they achieved target blood pressure reduction. At the end of this maintenance treatment, 24 hour intra-arterial blood pressure monitoring was repeated. Twelve patients were satisfactorily controlled on 120 mg b.i.d. CR diltiazem, three on 240 mg twice daily and one on 360 mg twice daily. During rest and exercise, blood pressure and heart rate were significantly lower after treatment with CR diltiazem than before treatment. The hypotensive effect of diltiazem was maintained throughout the 12 hour dosing interval and the early morning blood pressure response was blunted. No adverse effects or ECG abnormalities were reported. It was concluded that CR diltiazem 120 mg, administered twice daily to a total daily dose of between 240 mg and 720 mg, is effective and well tolerated in the treatment of mild to moderate essential hypertension.
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  • 4
    ISSN: 1432-1041
    Keywords: Ranolazine ; angina ; stress testing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ranolazine (RS-43285) has been shown to possess significant anti-ischaemic properties in a canine model of reversible myocardial ischaemia. The clinical efficacy of this new agent was assessed by a single blind, placebo controlled study of 14 patients with chronic stable angina. A 2 week placebo phase was followed by therapy with 30 mg and 60 mg of ranolazine tid for 2 weeks each. Graded, symptom limited treadmill exercise tests were performed at the end of each phase, 1.5 h (AM) and 7 h (PM) after the morning dose. An additional exercise test 1.5 h after the first dose of 30 mg was included to assess the acute dose response. In the AM study, the mean exercise time increased from 6.9 min (placebo) to 7.8 min after the first dose of 30 mg and to 8.2 min and 8.5 min respectively at the end of 30 mg and 60 mg phases. In the PM study, exercise time improved from 6.5 min (placebo) to 8.2 min and 7.8 min respectively at the end of 30 mg and 60 mg phases. The time to onset of angina showed a similar improvement. No significant changes were observed in the resting and peak exercise heart rates and blood pressure. This preliminary study suggests that ranolazine may significantly prolong exercise time in patients with stable coronary artery disease without altering heart rates and blood pressure.
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  • 5
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 88 (1988), S. 7459-7467 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Considering a one-dimensional array of diffusively coupled Brussellators, we examine the bifurcations of the steady homogeneous solution to steady but spatially inhomogeneous structures. Several important aspects of such bifurcations are related to branching (see below) of the fixed point of a four-dimensional conservative map. In addition to the usual period doubling ("wavelength doubling'' in our terminology) observed in case of two-dimensional maps, the four-dimensional map is seen to exhibit a new type of branching, namely, giving rise to an invariant curve in phase space. In case of subthreshold branching of either type, the steady homogeneous solution bifurcates to either a "wavelength-two'' or a quasiperiodic solution. In case of superthreshold branching, on the other hand, bifurcations involving more complicated spatial and temporal behavior are possible. Other relevant questions are dealt with.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    Journal of Mathematical Physics 29 (1988), S. 1979-1981 
    ISSN: 1089-7658
    Source: AIP Digital Archive
    Topics: Mathematics , Physics
    Notes: Previous calculations of the Ricci curvature for the manifold Diff Diff(S1)/S1 are extended to Diff(S1)/SL(2@SR). These manifolds are distinguished by being coadjoint orbits of Diff(S1) which admit compatible symphectic and complex structures, making them Kähler manifolds.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 183 (1959), S. 1613-1613 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] It has been shown elsewhere8 that dehydrogenated coals (for example, by Vesterberg's technique dehydrogenation carried out with sulphur below the decomposition point of coal) do not yield any tar and that the char yield increases proportionately to the alicyclic carbon content of coal at the ...
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 175 (1955), S. 1046-1047 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] It has been observed that some factor present in the endosperm has a distinct inhibitory effect on the growth of the rice embryo kept under water or grown in air. Experiments were carried out with husked rice grain (variety Bhasamanik) from which different fractions of endosperm were removed, kept ...
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 193 (1962), S. 267-268 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Whether acidic or alkaline permanganate is used, the reaction on coal has been found to be immediate and vigorous even at room temperature, and it does not cease at any particular point and may well continue to the point of complete degradation of coal into water-soluble products. Such products ...
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters A 111 (1985), S. 256-260 
    ISSN: 0375-9601
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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