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Biomedical subjects

H Drexler

Publications and source records attributed to H Drexler.

At least 19 recordsLinked to original sources
PubMed1999

Endothelial dysfunction in human disease.

The vascular endothelium plays a key role in the local regulation of vascular tone by the release of vasodilator substances (i.e. endothelium-derived relaxing factor (EDRF = nitric oxide, NO) and prostacyclin) and vasoconstrictor substances (i.e. thromboxane A2, free radicals, or endothelin). Using either agents like acetylcholine or changes in flow to stimulate the release of EDRF (NO), clinical studies have revealed the importance of EDRF in both basal and stimulated control of vascular tone in large epicardial coronary arteries and in the coronary microcirculation. The regulatory function of the endothelium is altered by cardiovascular risk factors or disorders such as hypercholesterolemia, chronic smoking, hypertension or chronic heart failure. Endothelial dysfunction appears to have detrimental functional consequences as well as adverse longterm effects, including vascular remodelling. Endothelial dysfunction is associated with impaired tissue perfusion particularly during stress and paradoxical vasoconstriction of large conduit vessels including the coronary arteries. These effects may cause or contribute to myocardial ischemia. Several mechanisms may be involved in the development of endothelial dysfunction, such as reduced synthesis and release of EDRF or enhanced inactivation of EDRF after its release from endothelial cells by radicals or oxidized low-density lipoprotein (LDL). Increased plasma levels of oxidized LDL have been noted in chronic smokers and are related to the extent endothelial dysfunction, raising the possibility that chronic smoking potentiates endothelial dysfunction by increasing circulating and tissue levels of oxidized LDL. In heart failure, cytokines and/or reduced flow (reflecting reduced shear stress) may be involved in the development of endothelial dysfunction and can be reversed by physical training. Other mechanisms include an activated renin-angiotensin system (i.e. postmyocardial infarction) with increased breakdown of bradykinin by enhanced angiotensin converting enzyme (ACE) activity. There is evidence that endogenous bradykinin is involved in coronary vasomotor control both in coronary conduit and resistance vessels. ACE inhibitors enhance endothelial function by a bradykinin-dependent mechanism and probably also by blunting the generation of superoxide anion. Endothelial dysfunction appears to be reversible by administering L-arginine, the precursor of nitric oxide, lowering cholesterol levels, physical training, antioxidants such as vitamin C, or ACE inhibition.

Acetylcholine↗
PubMed1999

Effect of vitamin E on endothelial vasodilator function in patients with hypercholesterolemia, chronic smoking or both.

OBJECTIVES: The purpose of this study was to test the hypothesis that long-term supplementation with Vitamin E improves endothelium-dependent relaxation in hypercholesterolemia patients and/or chronic smoking, two risk factors that have been shown to be associated with increased radical formation. BACKGROUND: Experimental evidence suggests that oxidized low density lipoprotein (LDL) impairs endothelium-dependent relaxation, and vitamin E, a lipid-soluble antioxidant, reduces the oxidation of LDL. METHODS: Thirteen subjects with hypercholesterolemia, 14 smokers and 15 hypercholesterolemic smokers were enrolled in a double-blind, placebo-controlled study. After baseline measurements of plasma autoantibodies against oxidized LDL and assessment of endothelium-dependent relaxation using intra-arterial forearm infusions of acetylcholine, participants within each group were randomly assigned in a 1:2 fashion to receive either placebo or vitamin E for 4 months, when plasma levels of autoantibodies against oxidized LDL and vascular function were reassessed. RESULTS: Vitamin E significantly augmented endothelium-dependent relaxation in hypercholesterolemic smokers but not in patients with either hypercholesterolemia or chronic smoking. At baseline, hypercholesterolemic smokers had significantly higher autoantibody levels against oxidized LDL (compared with the other two groups), which were significantly reduced after 4 months of vitamin E supplementation. There was a significant relationship between improvement in acetylcholine-induced vasodilation and the change in autoantibody titer against oxidized LDL (r = -0.59; p = 0.002). CONCLUSIONS: Long-term vitamin E supplementation improves endothelium-dependent relaxation in forearm resistance vessels of hypercholesterolemic smokers, which are characterized by increased levels of autoantibodies against oxidized LDL. These findings may suggest that the beneficial effect of vitamin E is confined to subjects with increased exposure to oxidized LDL.

Acetylcholine↗
PubMed1999

Early angiographic results after revascularization by minimally invasive direct coronary artery bypass (MIDCAB).

OBJECTIVE: Anastomosing the left anterior descending artery (LAD) by use of the internal mammary artery (IMA) via an anterior minithoracotomy represents the most commonly performed minimally invasive direct coronary artery bypass (MIDCAB). However, little is known about angiographic results beyond patency rates. METHODS: Therefore, a retrospective analysis of 205 consecutive control angiographies was performed evaluating anastomototic patency as well as the angiographic morphology of the left IMA and the LAD. RESULTS: The overall anastomotic patency rate was 98.0%. As a result of incomplete IMA preparation (6-15 cm) large side branches (n = 4), or an IMA course under tension (n = 6) were occasionally observed. Despite a tension-free course, the IMA appeared fixed to the chest wall without functional compromise in 21 cases. A restrictive thrombus formation occurred once, IMA dissection was not seen. Two of the grafts developed spasms. A distal IMA stenosis >50% was seen in five cases. Stenosis of the anastomosis (>50%) itself was found once, as well as unexpected malinsertation to diagonal branches (n = 4). Compared with preoperative angiograms, de novo stenoses of the LAD were assessed proximal (14< or =50%, 2>50%) and distal (15< or =50%, 2>50%) to the anastomosis. Elevation of the LAD out of the vascular bed was an additional finding (n = 12) in a few cases. CONCLUSIONS: The overall patency of MIDCAB-LAD-grafting appears to be equivalent to conventional IMA grafting to the LAD. Particular angiographic findings, however, may be directly associated to the applied surgical technique.

Adult↗
PubMed1998

Vitamin C improves endothelial function of conduit arteries in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is associated with endothelial dysfunction including impaired endothelium-mediated, flow-dependent dilation (FDD). There is evidence for increased radical formation in CHF, raising the possibility that nitric oxide is inactivated by radicals, thereby impairing endothelial function. To test this hypothesis, we determined the effect of the antioxidant vitamin C on FDD in patients with CHF. METHODS AND RESULTS: High-resolution ultrasound and Doppler was used to measure radial artery diameter and blood flow in 15 patients with CHF and 8 healthy volunteers. Vascular effects of vitamin C (25 mg/min IA) and placebo were determined at rest and during reactive hyperemia (causing endothelium-mediated dilation) before and after intra-arterial infusion of N-monomethyl-L-arginine (L-NMMA) to inhibit endothelial synthesis of nitric oxide. Vitamin C restored FDD in patients with heart failure after acute intra-arterial administration (13.2+/-1.7% versus 8.2+/-1.0%; P<.01) and after 4 weeks of oral therapy (11.9+/-0.9% versus 8.2+/-1.0%; P<.05). In particular, the portion of FDD mediated by nitric oxide (ie, inhibited by L-NMMA) was increased after acute as well as after chronic treatment (CHF baseline: 4.2+/-0.7%; acute: 9.1+/-1.3%; chronic: 7.3+/-1.2%; normal subjects: 8.9+/-0.8%; P<.01). CONCLUSIONS: Vitamin C improves FDD in patients with CHF as the result of increased availability of nitric oxide. This observation supports the concept that endothelial dysfunction in patients with CHF is, at least in part, due to accelerated degradation of nitric oxide by radicals.

Administration, Oral↗
PubMed1998

Expression of Smad1 and Smad2 during embryogenesis suggests a role in organ development.

Smad proteins are intracellular signalling molecules and putative transcription factors that transduce signals elicited by members of the transforming growth factor beta (TGF-beta) superfamily. By comparing the expression of Smad1 and Smad2 during embryonic development, we show that mRNAs of both Smad isoforms are present in a variety of tissues. The major sites of expression of both Smads can be correlated with the expression domains of several members of the TGF-beta superfamily. Our expression data suggest that Smad proteins are involved in organ development, particularly that of organs arising from mesenchymal-epithelial interactions. A second site of strong expression is the central nervous system. Transcriptional control mediated by Smad1 and Smad2, therefore, may exert an important function in differentiation processes of embryonic development that are controlled by ligands of the TGF-beta superfamily.

Animals↗
PubMed1998

The mercury concentration in breast milk resulting from amalgam fillings and dietary habits.

Health risks from amalgam fillings are a subject of controversy. In Germany it is not advised to use amalgam fillings during breast feeding. Objectives of this study were to examine the concentration of mercury in human breast milk and the confounders which may modify the mercury levels. Women who gave birth between August 1995 and May 1996 in a district hospital were asked to participate in the study. The examination included a standardized anamnesis and an inspection of the teeth by an dentist. Blood and urine samples of 147 women and breast milk samples of 118 women were collected in the first week after birth. After 2 months of breast feeding a second breast milk sample was collected from 85 of women. Mercury was measured by cold-vapor atomic absorption spectrometry. The concentration of mercury in the breast milk collected immediately after birth showed a significant association with the number of amalgam fillings as well as with the frequency of meals. Urine mercury concentrations correlated with the number of amalgam fillings and amalgam surfaces. In the breast milk after 2 months of lactation, the concentrations were lower (mean: <0.25 microg/L; range <0.25-11.7 microg/L) compared with the first sample (mean: 0.90 microg/L; range <0.25-20. 3 microg/L) and were positively associated with the fish consumption but no longer with the number of the amalgam fillings. Accordingly, the additional exposure to mercury of breast-fed babies from maternal amalgam fillings is of minor importance compared to maternal fish consumption.

Adult↗
PubMed1998

Occupationally related tumors in tar refinery workers.

BACKGROUND: The study comprised 606 workers with tar-induced dermatosis employed in a German tar refinery. During the period from 1946 to 1996 they were recognized as having an occupational disease. OBJECTIVE: The aim of this study was to characterize the histologic findings and the localization of the occupational dermatosis and to determine the latency period of the carcinomas from the beginning of exposure in the tar refinery to the first occurrence of malignant skin tumors. Furthermore, the study aimed to check whether other skin changes were frequently diagnosed in addition to known tar-induced tumors. METHODS: The data were collected retrospectively from the documents of the Employer's Liability Insurance Association. RESULTS: Surgical removal of 4754 skin tumors was documented up to the end of 1996 in the study. In 90% of cases the histologic diagnosis was confirmed. Among other conditions, this yielded 2490 precancerous stages, 380 squamous cell carcinomas, 218 basal cell carcinomas, and 182 keratoacanthomas. The skin tumors were found mainly in the facial area, as well as on the forearms and hands. Latency from the first exposure in the tar refinery until manifestation of tar-induced dermatosis covered a period of 57 years. CONCLUSION: In comparison to the general population, the ratio of squamous cell to basal cell carcinomas was shifted toward the squamous cell carcinomas (1.7:1). Sunlight is known to be a cofactor in the pathogenesis of keratosis, squamous cell carcinomas, and basal cell carcinomas. However, the difference in location of these tumors shows that the role sunlight plays in the pathogenesis of precancerous lesions and squamous cell carcinomas may be overvalued. The latency period from the beginning of exposure to the manifestation of squamous cell carcinomas could not be evaluated because of an intervention bias as a result of preventive excisions of precancerous lesions. The frequent occurrence of keratoacanthomas (in 18.7% of the workers) and the early age at which this disease became manifest relative to the general population (median, 55 years) indicate that employment in a tar refinery can primarily or secondarily cause keratoacanthomas.

Adolescent↗
PubMed1998

Inducible nitric oxide synthase in skeletal muscle of patients with chronic heart failure.

OBJECTIVES: The expression and localization of inducible nitric oxide (NO) synthase (NOS II) was evaluated as a source of NO which has been shown to affect muscle contraction. BACKGROUND: Advanced stages of chronic heart failure are associated with systemic activation of cytokines which have been shown to stimulate the expression of NOS II in various cell types, including myocytes. We hypothesized that systemic cytokine activation could lead to expression of NOS II in skeletal muscle of patients with chronic heart failure. METHODS: Skeletal muscle specimens were obtained by percutaneous needle biopsy in six normal volunteers and eight patients with heart failure (New York Heart Association class III). Electron microscopy immunocytochemistry (immunogold labeling) with specific anti-NOS antibodies was utilized to elucidate the intracellular localization of NOS II and neuronal NO synthase (NOS I) in myocytes of skeletal muscle. Reverse transcriptase, competitive polymerase chain reaction (PCR) was applied to quantify NOS II mRNA in skeletal muscle. RESULTS: Inducible nitric oxide synthase was readily expressed in the cytosol of skeletal muscle myocytes; NOS I expression was sparse. Polymerase chain reaction results indicated that NOS II gene expression is increased in patients with chronic heart failure. CONCLUSIONS: Inducible NO synthase is expressed in human skeletal muscle and its gene expression is increased in patients with severe heart failure. Given the experimental evidence that NO can attenuate contractile performance of skeletal muscle and can mediate muscle wasting, an increased local production of NO in skeletal muscle by NOS II may have important implications for patients with severe heart failure.

Adult↗
PubMed1998

Expression, activity and functional significance of inducible nitric oxide synthase in the failing human heart.

OBJECTIVES: The study was designed to evaluate the functional impact of nitric oxide (NO) generation within the myocardium on cardiac contraction in the failing human heart. BACKGROUND: Heart failure is associated with activation of cytokines and expression of inducible nitric oxide synthase (NOS II), which generates NO from L-arginine. Nitric oxide has been shown to modulate myocardial performance, raising the possibility that cardiac generation of NO by NOS II modulates cardiac contraction in the failing human heart. METHODS: Left ventricular (LV) tissue of 24 patients with end-stage heart failure was obtained during cardiac transplantation. Gene expression of NOS II and endothelial NO-synthase (NOS III) was quantified by competitive reverse transcription-polymerase chain reaction and compared to tissues of five nonfailing donor hearts. Nitric oxide synthase II activity was determined by citrulline assay and related to changes in force of contraction induced by the beta-adrenergic agonist isoproterenol, NO-donors and/or N-mono-methyl-L-arginine (L-NMMA), an inhibitor of NOS. RESULTS: While NOS III mRNA was reduced in failing hearts, NOS II mRNA was increased in failing LV tissue and correlated with NOS II activity. High NOS II activity was associated with early relaxation and impaired responsiveness to beta-adrenergic stimulation, that is, the inotropic response to isoproterenol in failing hearts was inversely related to NOS II activity (r=0.61, p < 0.005). Nitric oxide donors or L-NMMA did not affect myocardial performance in failing hearts at baseline. However, L-NMMA enhanced the positive inotropic response to beta-adrenergic stimulation in failing hearts with high NOS II activity. Nitric oxide donors attenuated the isoproterenol-induced increase in force of contraction of failing hearts. CONCLUSIONS: Cardiac production of NO by NOS II attenuates the positive inotropic effects of beta-adrenergic stimulation and hastens relaxation in failing human hearts.

Adrenergic beta-Agonists↗
PubMed1998

Angiotensin-converting enzyme gene expression in skeletal muscle in patients with chronic heart failure.

BACKGROUND: Skeletal muscle factors may influence functional limitation in patients with heart failure. The renin-angiotensin system is activated in chronic heart failure. Treatment with angiotensin-converting enzyme (ACE) inhibitors improve symptoms and prognosis. The goal of this study was to quantify and localize skeletal muscle ACE-mRNA in patients with chronic heart failure and in control subjects, and to elucidate skeletal muscle fiber area and capillary density. METHODS AND RESULTS: Biopsies from the lateral vastus muscle were taken from 9 patients before and after treatment with enalapril and in 10 control subjects. ACE-mRNA was quantified with reverse transcription polymerase chain reaction. Immunohistochemistry was used to localize ACE within skeletal muscle. No difference in ACE-mRNA transcripts between patients and control subjects was detected, nor did ACE gene expression change after treatment with enalapril. The number of ACE-mRNA transcripts was related to muscle fiber area, whereas an inverse relationship between the number of ACE transcripts and capillary density was found. ACE was detected in the endothelial cells of capillaries in skeletal muscle. CONCLUSION: ACE is expressed in skeletal muscle and is confined to endothelial cells. The close relationship between capillary density and number of ACE transcripts indicate that activation of the renin-angiotensin system has an impact on capillary growth.

3-Hydroxyacyl CoA Dehydrogenases↗