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  • 1
    ISSN: 1432-1440
    Keywords: HIV-1 ; Endothelins ; Endothelin-1 ; Cytokine ; Retinal microangiopathic syndrome ; Vascular disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Endothelin-1 is a recently identified cytokine with potent vasoconstrictor activity which is associated with various diseases involving blood vessels. HIV-1 related retinal microangiopathic syndrome is a frequent finding in patients with AIDS or AIDS-related complex, presenting predominantly with retinal cotton-wool spots. We investigated 55 HIV-1 infected patients by ophthalmoscopy and for endothelin-I immunoreactivity in plasma and an additional 76 HIV-1 infected patients only for endothelin-1 levels. For reference values 13 age-matched healthy subjects were studied. In 18 of 55 patients (33%) investigated ophthalmoscopically we found evidence of microangiopathic syndrome. Overall, the mean endothelin-1 immunoreactivity in plasma of HIV-1 infected patients was significantly elevated as compared to controls (4.28 ± 3.62 versus 2.72 ± 0.67 fmol/ml, P 〈 0.0001). HIV-1 infected patients with retinal microangiopathic syndrome had significantly higher plasma levels of endothelin-1 immunoreactivity (4.59 ± 1.38 fmol/ ml) compared to HIV-1 infected patients without microangiopathic syndrome (3.18 ± 1.64 fmol/ml, P = 0.003). Correlation analysis revealed that endothelin-1 immunoreactivity in plasma had no significant association with disease progression, CD4 cell count, β2-mi-croglobulin, neopterin, or age. Endothelin-1 immunoreactivity in plasma was correlated exclusively with retinal microangiopathic syndrome in one or both eyes (r = 0.45, P = 0.0006) and with the number of cotton-wool spots (r = 0.50, P = 0.0001). In conlusion, HIV-1 related retinal microangiopathic syndrome is associated with elevated plasma levels of endothelin-1. By virtue of its potent vasoconstrictor activity endothelin-1 may be involved in the pathogenesis of HIV-1 related vascular disease.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Congestive heart failure ; PDE inhibition ; Positive inotropic action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Enoximone, a phosphodiesterase-inhibitor, is a potent inotropic vasodilator agent that causes a marked improvement in hemodynamics in patients with congestive heart failure. The acute effects of oral enoximone on rest and exercise hemodynamics, ejection fraction, aerobic metabolism, exercise capacity, and arrhythmias were studied in 11 patients with moderate to moderately severe dilative cardiomyopathy after 8 days of enoximone (100 mg tid) in addition to baseline therapy (diuretics and digitalis). The cardiac index increased from 2.44±0.45 to 2.72±0.50 l/min/m2 (p〈0.01) at rest and from 4.00±0.96 to 4.75±0.95 l/min/m2 (p〈0.005) during exercise. Pulmonary wedge pressure decreased from 16.8±7.3 to 12.5±6.5 mmHg (p〈0.005) at rest and from 28.2±8.0 to 24.5±10.3 mmHg (p〈 0.05) during exercise. Systemic vascular resistance decreased from 1608±243 to 1495±300 dynes*sec*cm−5 (p〈0.05) at rest and from 1152±155 to 1027±236 dynes*sec*cm−5 (ns) during exercise. The anaerobic threshold, which was recorded simultaneously, increased from 13.2±2.7 to 15.5± 2.5ml/kg/min VO2 (p〈0.02). The radionuclide ventriculography ejection fraction improved from 21.7±5.0 to 28.1±9.1% (p〈0.01) during exercise; the changes at rest were not significant (20.8±6.2 vs 25.8±8.4%). Exercise tolerance showed an increase of 16% (492±133 to 573±135 sec, p〈 0.005). The resting heart rate remained unchanged (81.8±13.4 vs 81.8±11.9). Interestingly, 24-h Holter monitoring revealed more or new repetitive arrhythmias in 9/11 patients. Short-term therapy with oral enoximone enhances ventricular performance by increasing cardiac contractility and lowering vascular resistance, both of which extend exercise tolerance and improve aerobic metabolism. Potential proarrhythmic effects need further evaluation, however.
    Type of Medium: Electronic Resource
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