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  • 1
    ISSN: 1432-1238
    Keywords: Key words Hypoxia ; Ischemia ; Acute phase proteins ; Cardiac arrest ; Infections
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Inflammation and hypoxia are frequently associated, but their interaction is poorly understood. In vitro studies have shown that hypoxia stimulates the genes of acute phase proteins (APP) and cytokines known to induce APP. We decided to determine kinetics and potential determinants of an acute phase response after cardiac arrest and to assess whether isolated moderate hypoxia can induce APP in humans in vivo. Design: Prospective, observational study in patients and human experiment. Setting: Tertiary care university hospital. Patients and participants: 22 patients after primarily successful cardiopulmonary resuscitation (CPR) and 7 healthy volunteers. Interventions: None in patients; exposure of volunteers to simulated altitude (460 torr/6 h). Results: Following CPR, type-1 APP (C-reactive protein, α1-acidglycoprotein, serum amyloid A) and type-2 APP (haptoglobin, α1-antitrypsin) increased consistently within 1–2 days and the ’negative' APP transferrin was downregulated. This APP response occurred irrespective of the cause of arrest, the estimated time of anoxia, clinical course or patient outcome and was not different in patients with and without infectious complications. Exposure of healthy volunteers to less severe but more prolonged hypoxia did not induce APP, although a time dependent increase of serum erythropoietin (EPO) was measurable under these conditions, indicating the activation of oxygen dependent gene expression. Conclusions: (i) A marked acute phase response occurs regularly after cardiac arrest, but within the complexity of this situation the severity of hypoxia is not a predominant determinant of this response. (ii) Despite in vitro evidence for similarities in the oxygen dependent regulation of APP and EPO production, the oxygen sensitivity of these proteins in vivo is different. (iii) Measurements of APP are not revealing regarding infectious complications in the early phase after CPR.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 52 (1997), S. 387-390 
    ISSN: 1432-1041
    Keywords: Key words CYP2D6 ; Fluoxetine ; Maprotiline; CYP2C19 ; CYP3A4 ; CYP1A2 ; antide-pressant therapy ; ultra-rapid metaboliser
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Case: We are reporting about a patient with major depression who failed to respond to pharmacotherapy due to ultra-rapid metabolism of maprotiline. Under daily oral doses of 175 mg maprotiline, the patient's metabolic ratio (MR) for maprotiline in plasma was 9.2 (expected MRp: 2.4) and the clearance of maprotiline (CLM) was 4190 ml · min−1 (expected CLM = 1220 in extensive metabolisers of CYP2D6). Results: The patient's MRurine for sparteine was 0.5, which is within the range for extensive metabolisers of CYP2D6. Genotyping did not show a duplication of the CYP2D6L allele. The patient's caffeine half-life was 10 h, thus, precluding ultra-rapid metabolism for CYP1A2. The therapeutic regimen was changed to coadministration of 200 mg maprotiline and 20 mg fluoxetine once per day in order to inhibit metabolism via CYP2D6. Subsequently, MRp of maprotiline (4.9) and CLM were reduced (1900 ml · min−1; expected CLM in poor metabolisers: of CYP2D6 364). This regimen improved the clinical outcome of the underlying disease. Conclusion: We conclude that for the non-response seen with maprotiline, P450 isozymes other than CYP2D6 or CYP1A2 are responsible. As CYP2C19 is involved in the metabolism of a number of tricyclic antidepressants it may be a candidate for ultra-rapid metabolism in this patient.
    Type of Medium: Electronic Resource
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