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  • 1
    Electronic Resource
    Electronic Resource
    CP-123,369: A potent, orally active immunosuppressive agent (1995)
    Springer
    Inflammation research 44 (1995), S. S183 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01778322
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  • 2
    Electronic Resource
    Electronic Resource
    Ion channel modulation as a drug discovery target in inflammatory diseases (1996)
    Springer
    Inflammation research 45 (1996), S. 435-437 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02252312
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  • 3
    Electronic Resource
    Electronic Resource
    The safety of ranitidine in over a decade of use (1997)
    Oxford BSL : Blackwell Science
    Alimentary pharmacology & therapeutics 11 (1997), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Ranitidine hydrochloride (Zantac) is one of the most extensively studied and widely used drugs of all time. This has provided an excellent opportunity to define its safety profile. Methods: Data from 189 controlled clinical trials in which more than 26000 patients received daily doses of ranitidine for 4 weeks or more were reviewed. More than 80% of patients were treated with up to 300 mg ranitidine daily; the remaining patients received doses of up to 1200 mg daily. Eighty-seven trials were placebo controlled. Analyses of post-marketing surveillance and a database of all spontaneously reported adverse events were also evaluated. Results: Overall in the clinical trial programme adverse events were reported by 20% of those receiving ranitidine compared with 27% of those receiving placebo. The pattern of events was similar in all treatment groups with no evidence of dose-related toxicity in regimens encompassing an eightfold range of therapeutic doses. Similarly in a programme of studies designed to evaluate a dose of ranitidine of 75  mg for non-prescription (over-the-counter) use in the treatment of heartburn, ranitidine was not associated with an adverse event profile distinct from that of placebo. Analysis of spontaneously reported adverse event data allowed identification of rare idiosyncratic events. Conclusions: Review of data from a large population of controlled clinical trials with analyses of postmarketing surveillance studies and spontaneously reported adverse events confirmed the excellent safety profile of ranitidine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.1997.136312000.x
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  • 4
    Electronic Resource
    Electronic Resource
    CARBOHYDRATE-MODULATED GENE EXPRESSION IN PLANTS (1996)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 47 (1996), S. 509-540 
    Details
    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Plant gene responses to changing carbohydrate status can vary markedly. Some genes are induced, some are repressed, and others are minimally affected. As in microorganisms, sugar-sensitive plant genes are part of an ancient system of cellular adjustment to critical nutrient availability. However, in multicellular plants, sugar-regulated expression also provides a mechanism for control of resource distribution among tissues and organs. Carbohydrate depletion upregulates genes for photosynthesis, remobilization, and export, while decreasing mRNAs for storage and utilization. Abundant sugar levels exert opposite effects through a combination of gene repression and induction. Long-term changes in metabolic activity, resource partitioning, and plant form result. Sensitivity of carbohydrate-responsive gene expression to environmental and developmental signals further enhances its potential to aid acclimation. The review addresses the above from molecular to whole-plant levels and considers emerging models for sensing and transducing carbohydrate signals to responsive genes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.arplant.47.1.509
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  • 5
    Electronic Resource
    Electronic Resource
    Alosetron repeat dose pharmacokinetics, effects on enzyme activities, and influence of demographic factors (2004)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 20 (2004), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim : To assess the pharmacokinetics of alosetron, its effect on in vivo enzyme activities, and influence of demographic factors during repeated dosing.Methods : Thirty healthy men and women received 1 mg oral alosetron twice-daily for 29.5 days and a single oral dose of a metabolic probe cocktail before and on the last day of alosetron dosing. Serum alosetron concentrations were measured on days 1, 8, 15, 22 and 29. Probe-substrate and metabolite concentrations were measured after each cocktail dose.Results : Alosetron accumulation in serum was negligible. Exposure to alosetron did not alter probe-metabolite/substrate ratios associated with CYP2C19, 2E1, 2C9, or 3A4 activity, but modestly decreased those associated with CYP1A2 and N-acetyltransferase activity. Systemic exposure to alosetron was higher in women, positively correlated with age and body mass index, and negatively correlated with CYP1A2 activity. Incidence of constipation was higher in women, but not associated with alosetron concentration.Conclusions : Single dose data can reliably predict the pharmacokinetics of alosetron after repeated doses. Alosetron exhibits limited potential for inhibition of cytochrome P450-mediated metabolism. Interindividual differences in alosetron pharmacokinetics associated with demographic factors may be related to strong dependence on metabolism by CYP1A2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.2004.02031.x
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  • 6
    Electronic Resource
    Electronic Resource
    Enhanced second-harmonic response and stability of corona-poled guest—host polycarbonate thin films (1995)
    Springer
    Journal of materials science 6 (1995), S. 228-234 
    Details
    ISSN: 1573-482X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Second-harmonic generation and spectroscopic absorption measurements were made to study the non-linear optical and stability properties of guest/host polycarbonate thin films in which the guest chromophores were oriented by corona poling. Optimum poling conditions were achieved at temperatures less than the glass-rubber transition temperatures. Stabilized order parameters as high as 0.23 and retention of orientational order as high as 86% were found. Stable, resonance-enhanced, values of the non-linear optical coefficient d 33, for the fundamental of 1.064 Μm, were as high as 31 pm V−1. This value is over four times that predicted by a simple thermodynamic model for isotropic materials. Hydrogen bonding between the guest and polycarbonate is proposed to account for the high d 33 coefficients and long-term stability of the films.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00187202
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  • 7
    Electronic Resource
    Electronic Resource
    Diagnostik der Myokardvitalität bei chronischer Myokardischämie mit nuklearmedizinischen Verfahren (1998)
    Springer
    Zeitschrift für Kardiologie 87 (1998), S. s092 
    Details
    ISSN: 1435-1285
    Keywords: Schlüsselwörter Myokardvitalität – Prognose – Koronarrevaskularisation – Ventrikelfunktion – Radionuklide ; Key words myocardial viability – hibernation – coronary revascularization – left ventricular function – radioisotopes – tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Non-invasive methods to identify absent or persistent myocardial viability have gained increasing importance in the therapeutic management and risk stratification of patients with ischemic left ventricular dysfunction. Myocardial scintigraphy using thallium-201 and positron emission tomography with metabolic imaging of myocardial glucose metabolism, using fluorine-18 fluoro-deoxyglucose, are today the most widely used nuclear methods for the assessment of myocardial viability. Besides the prediction of reversible regional and global myocardial dysfunction following coronary revascularization, both methods have demonstrated the ability to identify patient subgroups who will benefit most with regard to cardiac prognosis and survival and those patients in whom coronary revascularization has a limited effect with regard to survival and cardiac events. This short review summarizes the clinical impact of both imaging modalities on todays diagnostic approach in patients with ischemic left ventricular dysfunction.
    Notes: Zusammenfassung Nichtinvasive Verfahren zur Vitalitätserkennung haben in den letzten Jahren zunehmende Bedeutung bei der Frage der präoperativen Risiko- und Nutzenabschätzung von koronarrevaskularisierenden Verfahren erhalten. An nuklearmedizinischen Untersuchungsmethoden haben sich im klinischen Alltag die Thallium-201-Myokardszintigraphie sowie die Positronen-Emissions-Tomographie mit Fluor-18-Fluorodeoxyglukose bewährt. Neben der Vorhersage der Reversibilität von regionalen Wandbewegungsstörungen und damit auch der globalen Ventrikelfunktion erlauben beide Methoden die Identifizierung von Patientenpopulationen, die hinsichtlich ihrer Prognose am meisten von revaskularisierenden Verfahren profitieren werden. Diese Übersicht faßt den derzeitigen klinischen Stellenwert beider Methoden bei der Diagnostik der Myokardvitalität in Regionen mit chronischer Ischämie zusammen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003920050547
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  • 8
    Electronic Resource
    Electronic Resource
    Evaluation of the SOFA score: a single-center experience of a medical intensive care unit in 303 consecutive patients with predominantly cardiovascular disorders (2000)
    Springer
    Intensive care medicine 26 (2000), S. 1037-1045 
    Details
    ISSN: 1432-1238
    Keywords: Key words Severity of illness index ; Multiple organ failure ; Critically ill ; Morbidity ; Organ failure ; Outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To evaluate the use of the Sequential Organ Failure Assessment (SOFA) score, the total maximum SOFA (TMS) score, and a derived variable, the ΔSOFA (TMS score minus total SOFA score on day 1) in medical, cardiovascular patients as a means for describing the incidence and severity of organ dysfunction and the prognostic value regarding outcome. Design: Prospective, clinical study. Setting: Medical intensive care unit in a university hospital. Patients: A total of 303 consecutive patients were included (216 men, 87 women; mean age 62 ± 12.6 years; SAPS II 26.2 ± 12.7). They were evaluated 24 h after admission and thereafter every 24 h until ICU discharge or death between November 1997 and March 1998. Readmissions and patients with an ICU stay shorter than 12 h were excluded. Main outcome measure: Survival status at hospital discharge, incidence of organ dysfunction/failure. Interventions: Collection of clinical and demographic data and raw data for the computation of the SOFA score every 24 h until ICU discharge. Measurements and main results: Length of ICU stay was 3.7 ± 4.7 days. ICU mortality was 8.3 % and hospital mortality 14.5 %. Nonsurvivors had a higher total SOFA score on day 1 (5.9 ± 3.7 vs. 1.9 ± 2.3, p 〈 0.001) and thereafter until day 8. High SOFA scores for any organ system and increasing number of organ failures (SOFA score ≥ 3) were associated with increased mortality. Cardiovascular and neurological systems (day 1) were related to outcome and cardiovascular and respiratory systems, and admission from another ICU to length of ICU stay. TMS score was higher in nonsurvivors (1.76 ± 2.55 vs. 0.58 ± 1.39, p 〈 0.01), and ΔSOFA/total SOFA on day 1 was independently related to outcome. The area under the receiver-operating characteristic curve was 0.86 for TMS, 0.82 for SOFA on day 1, and 0.77 for SAPS II. Conclusions: The SOFA, TMS, and ΔSOFA scores provide the clinician with important information on degree and progression of organ dysfunction in medical, cardiovascular patients. On day 1 both SOFA score and TMS score had a better prognostic value than SAPS II score. The model is closely related to outcome and identifies patients who are at increased risk for prolonged ICU stay.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001340051316
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  • 9
    Electronic Resource
    Electronic Resource
    Long-term antiarrhythmic efficacy and safety of d-sotalol in patients with ventricular tachycardia and a low ejection fraction (1995)
    Springer
    Cardiovascular drugs and therapy 9 (1995), S. 437-443 
    Details
    ISSN: 1573-7241
    Keywords: d-sotalol ; ventricular tachycardia ; heart failure ; antiarrhythmic treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since in patients with ventricular tachycardia (VT) and compromised left ventricular function, antiarrhythmic therapy poses a particular problem, an open-label safety study of d-sotalol, a new class III antiarrhythmic agent, was performed. Thirteen patients with defined VT and a low left ventricular ejection fraction (LVEF) were treated with orally administered d-sotalol, 100 mg bid, and in a few patients 100 mg tid, in an open study. Patients were followed up for 35±11 months, with the longest follow-up amounting to 51 months. The data obtained suggest that d-sotalol was moderately effective as an antiarrhythmic agent, in particular with respect to premature ventricular contractions (PVCs) and coupled and repetitive PVCs. The beneficial effect appeared to persist on long-term treatment. d-Sotalol was well tolerated and no subjective or objective adverse reactions were observed. There were no signs of worsening of congestive heart failure, proarrhythmogenic activity, or torsades de pointes, although QT-prolongation was observed. There were no dropouts in the study. Two patients died: One patient with idiopathic dilated cardiomyopathy (with LVEF=11%) died suddenly after 38 months of follow-up and one patient after 17 months from recurrent myocardial infarction. Neither of these had shown recurrence of VT on 24 hour ambulatory ECG recordings. In conclusion, in this small group of patients d-sotalol appeared to be safe and well tolerated during long-term treatment of patients with VT and poor left ventricular function. There were clear suggestions of antiarrhythmic activity, reflected by the suppression of complex ventricular arrhythmias and by the absence of recurrent VT on long-term follow-up in the majority of patients. These results would encourage a larger, formal trial on the use of d-sotalol in this type of patients,.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00879033
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  • 10
    Electronic Resource
    Electronic Resource
    Ein neues resorbierbares Knochen-Knorpel-Ersatztransplantat (2000)
    Springer
    Der Orthopäde 29 (2000), S. 151-157 
    Details
    ISSN: 1433-0431
    Keywords: Schlüsselwörter Bioimplantat • Biomechanik •¶Knorpeldefekt • Knorpelregeneration •¶Mesenchymale Zelldifferenzierung ; Key words Bioimplant • Biomechanics • Cartilage ¶defect • Cartilage repair • Mesenchymal cell differentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Hyaline cartilage is thought to be unable to regenerate. All efforts so far – including autologous chondrocyte cell transplantation – to reconstruct cartilage defects in joints have not been totally convincing. However, mesenchymal cells are able to differentiate into chondrocytes under mechanical pressure conditions. In this study, an open porous resorbable two-layer “bioimplant” was constructed in which mechanical pressure was exerted onto mesenchymal cells when migrated into the open porous structure of the bioimplant. Differentiation of the cells into chondrocytes was thus induced. The bioimplants were implanted into the medial condyles of nine rabbits and left in place for eight or twelve weeks, respectively. In seven of these cases, cartilage formation was found, in contrary to the controls in which only connective tissue and bone had grown into the empty holes. The new bioimplants have proven their effectiveness in cartilage defect repair and might evolve in the future as a new alternative treatment of full thickness defects of joint surfaces.
    Notes: Zusammenfassung Gelenkknorpel gilt in der Regel als nicht regenerationsfähig. Bis jetzt durchgeführte Versuche zur Wiederherstellung des Gelenkknorpels, inklusive der Knorpelzelltransplantation, zeigten wenig erfolgversprechende Ergebnisse. Jedoch gibt es Hinweise, dass unter Druckbelastung mesenchymale Stammzellen sich in Knorpelzellen differenzieren können. In der vorliegenden Studie wurde ein offenporiges resorbierbares, zweischichtiges „Bioimplantat“ konstruiert, das nach Implantation in einen Knochen-Knorpel-Defekt die physiologischen Druckverhältnisse nachahmt und so eine Differenzierung von mesenchymalen Stammzellen zu hyalinem Knorpel ermöglicht. An 9 Kaninchen wurde dieses Bioimplantat an Knochenknorpeldefekten des Femurkondylus über 2 verschiedene Zeiträume erprobt und mit Leerlochversuchen verglichen. Durch die Bioimplantate gelang es im Gegensatz zu den Leerlochversuchen in 7 von 9 Fällen Bereiche mit hyalinartigem Knorpel zu induzieren. Die Methode scheint einen neuen erfolgsversprechenden Ansatz zur Reparation von Knorpeldefekten darzustellen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00003710
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