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H Vetter

Publications and source records attributed to H Vetter.

At least 19 recordsLinked to original sources
PubMed2007

[Effect of candesartan cilexetil with hydrochlorothiazide on blood pressure and ST-segment depression in patients with arterial hypertension].

OBJECTIVE: To examine the effect of candesartan cilexetil with hydrochlorothiazide (6 mg and 12.5 mg, respectively) on blood pressure and ST-segment depression during daily life of patients with treated but not controlled arterial hypertension (blood pressure taken at doctor's practice (3)140/90 mmHg, despite being on at least two antihypertensive drugs) PATIENTS AND METHODS: 51 patients (45 men, 17 women) with treated but reportedly uncontrolled hypertension were placed on self-measurement of blood pressure for 4 weeks of a run-in period and 8 weeks as a follow-up period. Combined 24-hour automatic blood pressure measurement (ABPM) and electrocardiography were done at the end of the run-in and the follow-up periods. Ten patients proved to be normotensive according to the self-measurement and ABPM after the run-in period (group A), while 41 were still uncontrolled according to both methods (group B). In group B the least efficacious component of the antihypertensive medication was replaced by candesartan with hydrochlorothiazide (C + HCT) and any changes in blood pressure and ST-segment depression analysed after 8 weeks of follow-up in both groups. RESULTS: In group A no significant blood pressure change was observed between run-in- and follow-up periods. But in group B (n=41) the self-measured systolic blood pressure had significantly decreased (155/84 mmHg compared with [vs] 147/81 mmHg; p<0.0073) as had the systolic 24-h ABPM (148/81 mmHg vs 137/753 mmHg; p<0.0015) after C + HCT had replaced the previous noneffective medication. After the run-in period 15 patients of group B had ST-segment depression (1 mm of horizontal or descending depression for at least 1 minute). In 16 other patients of group B and in all patients of group A no ST depressions were recorded. At the end of the follow-up period significant reduction of mean ischemic burden per patient (106 vs 72 minutes), of total ischemic events (228 vs 153) and of mean duration of ST depression (372 vs 210 seconds) had occurred. CONCLUSIONS: Replacing candesartan + hydrochlorothiazide for previously ineffective antihypertensive drugs in patients with uncontrolled arterial hypertension significantly reduced both blood pressure and ST-segment depression during daily life.

Aged↗
PubMed2007

Application of the "-Omic-" technologies in phytomedicine.

The proof of efficacy of phytopreparations and the determination of their mode of action are permanent challenges for an evidence-based phytotherapy. The technology platform of genomics, proteomics and metabolomics ("-omic-" technologies) are high-throughput technologies. They increase substantially the number of proteins/genes that can be detected simultaneously and have the potential to relate complex mixtures to complex effects in the form of gene/protein expression profiles. Provided that phytopreparation-specific signatures in the form of gene/protein expression profiles can be developed, these technologies will be useful for the chemical and pharmacological standardization and the proof of the toxicological potential of a plant extract. Over a long-term perspective they may economize the proof of efficacy, the determination of the mode of action of phytomedicines and allow to investigate herbal extracts without prominent active principle(s). The application of this genomics revealed already that gene expression profiles induced by single drugs and the ones induced by the combination of the same drugs can be entirely different. These results make the information of the mode of action of isolated "active principles/lead substances" of phytopreparations questionable. The application of the "-omic-" technologies may lead to a change of paradigms towards the application of complex mixtures in medicine and open the new field of phytogenomics, -proteomics and -metabolomics.

Drug Synergism↗
PubMed2006

[The modified Bonn Malmö protocol (MBMP) in the treatment of acquired haemophilia A].

BACKGROUND AND OBJECTIVE: Autoantibodies directed against clotting factors can induce life threatening bleeding with a mortality rate up to 22%. Although the incidence of the disease is low (1-4 x 10(-6)), costs of treatment due to long-term clotting factor substitution can be enormous. Aim of an optimal treatment strategy should be to control bleedings by a rapid and safe elimination of the inhibitor and reinducing long-term immune tolerance. PATIENTS AND METHODS: Treatment of 48 patients with acquired haemophilia A (m=20, f =28, age 61.3 (SD 16.4)), the largest patient collective world-wide, was monitored for a mean of 48 months. Three patients received only conservative treatment. 45 patients were treated intensively by a multimodal strategy including: 1. immunoadsorption for antibody elimination; 2. FVIII substitution; 3. intravenous immunoglobulin substitution and 4. immunosuppression. The times required for inhibitor elimination, factor VIII substitution and the duration of the MBMP were documented. RESULTS: In 45 patients with a high titre critical bleeding was controlled immediately after the initiation of MBMP. There were no deaths from bleeding or the treatment. Inhibitor levels decreased to undetectable levels within a median of 3 days (95% CI, 3-7 days), factor substitution was terminated within a median of 13 days (95% CI, 10-16 days) and the treatment was completed within a median of 15 days (95% CI, 13-17 days). The overall response rate for complete remission (CR) was 91%. When cancer patients were excluded, the CR rate was 97%. CONCLUSION: Considering the short duration and amount of factor VIII substitution, the short time of hospitalization and the long-term median follow up of 48 months without bleeding events, the MBMP appears to have a modifying effect on the immunological response.

Aged↗
PubMed2006

Toll-like receptor (TLR) 4 polymorphisms are associated with a chronic course of sarcoidosis.

The aetiology of sarcoidosis, an inflammatory granulomatous multi-system disorder, is unclear. It is thought to be the product of an unknown exogenous antigenic stimulus and an endogenous genetic susceptibility. Toll-like receptors (TLR) are signal molecules essential for the cellular response to bacterial cell wall components. Lipopolysaccharide (LPS), for example, binds to TLR 4. Two different polymorphisms for the TLR4 gene (Asp299Gly and Thr399Ile) have been described recently. This leads to a change in the extracellular matrix function of TLR4 and to impaired LPS signal transduction. We genotyped a total of 141 Caucasian patients with sarcoidosis and 141 healthy unrelated controls for the Asp299Gly and Thr399Ile polymorphisms in the TLR4 gene. The mutations were identified with polymerase chain reaction followed by restriction fragment length polymorphism (RFLP) analysis. Among sarcoidosis patients the prevalence for each Asp299Gly and Thr399Ile mutant allele was 15.6% (22/141). In the control group the prevalence was 5.67% (8/141) (P = 0.07). In the subgroup of patients with acute sarcoidosis there was no difference in the control group (P = 0.93), but there was a highly significant association between patients with a chronic course of sarcoidosis and TLR4 gene polymorphisms (P = 0.01).

Acute Disease↗
PubMed2004

Comparison of in vitro-activity of commonly used topical glucocorticoids on cytokine- and phospholipase inhibition.

BACKGROUND AND OBJECTIVES: Topical glucocorticoids (GCs) are potent inhibitors of cellular inflammatory mediator production. Differences in receptor binding activities are believed to correlate with inhibition of mediator release and anti-inflammatory efficacy in vivo. To further assess this hypothesis we compared in cultured human monocytes the inhibitory activity of classic synthetic GCs on leukotriene B4 (LTB4), prostaglandin E2 (PGE2), interleukin 1 beta (IL-1beta) and c-phospholipase A 2 activity (cPLA2). METHODS: Normal human monocytes (10(5) /ml) were tested for 20 hrs with increasing concentrations (range 10(-12) -10(-5) M) of triamcinolone acetonide (TAA) compared to beclomethasone dipropionate (BDP), budesonide (BUD), dexamethasone (DEX), or the ethanol diluent together with 10 microg/ml of lipopolysaccharide (LPS). Mediator production and spontaneous cPLA subset 2-activity was determined by direct enzyme immunoassay methods. RESULTS: TAA at therapeutically relevant concentration (10(-8) M) inhibited significantly (p<0.01, n = 9) mediator production of TNF-alpha > IL-1beta > TxB2 > LTB subset 4 in a dose dependent manner by 75%, 65%, 41%, and 33%. IL-1beta inhibition at 10(-8) M by TAA (65%)> BDP (52%)> BUD (47%) was not different (ANOVA, p>0.2). Also spontaneous cPLA2-activity at 10(-8) M was inhibited to a similar degree (ANOVA, p> 0.6) by BUD (17.3%) > TAA (11.4%) > BDP (8.6%). In the same culture conditions spontaneous PGE2-secretion was inhibited by BDP (28.8%) > BUD (24.2%) > TAA (11.4%) with no significant effect for TAA. CONCLUSION: Clinically well established GCs have a similar inhibitory capacity on monocyte cytokine production and surprisingly only weak effects on AA-metabolism. Small receptor binding activity may account for the lack of cytokine inhibition by subtherapeutic (<10(-8) M) airway concentrations of TAA and BDP. Partial mediator inhibition by GCs at therapeutically known airway concentrations may be relevant to control bursts of airway inflammation during acute exacerbation but unfavourable to effectively delay progression of chronic airway inflammation.

Administration, Cutaneous↗
PubMed2004

Different mechanisms of action of beta2-adrenergic receptor agonists: a comparison of reproterol, fenoterol and salbutamol on monocyte cyclic-AMP and leukotriene B4 production in vitro.

BACKGROUND: Beta2-adrenergic receptor agonists have several effects on airway function, most of which are mediated in a variety of cell types resulting in increased c-AMP-production and inhibition of inflammatory mediator production. However, their stimulating effects on cAMP-production became known to be inversed by increasing phosphodiesterase (PDE) activity and degradation of cAMP. Therefore, in this study we have evaluated the efficacy of reproterol, a dual acting beta2-adrenoceptor agonist and PDE-inhibitor, as compared to salbutamol and fenoterol with respect to production of cAMP and LTB4 in cultured monocytes. METHODS: Isolated human monocytes (10(5)/ml) were incubated (n = 9) in suspension with beta2-adrenoceptor agonists (10(-10) -10(-4) M) for 30 minutes with and without IBMX. Then, cAMP production was determined following treatment with Triton-X100. Production of LTB4 was measured following incubation of beta2-adrenoceptor agonists for 4 hrs in the presence of LPS (10 mg/ml). cAMP and LTB subset 4 were measured in culture supernatants by enzyme immunoassay. RESULTS: At 10(-5) M, production of cAMP was significantly stimulated by reproterol > fenoterol > salbutamol in a dose-dependent manner to an extent of *128%, *65%, 13% (*p<0.04) respectively. In contrast, LTB4-production was inhibited significantly to a similar degree by salbutamol and reproterol in a dose-dependent manner by 59% and 49% (10(-5) M, p<0.03), respectively, with decreasing inhibition (15%) after fenoterol. Following co-incubation with IBMX, cAMP production only increased significantly (p<0.002) after fenoterol (+110%) compared to salbutamol (+29%) and reproterol (+50%) (ANOVA, p<0.001). CONCLUSION: These data suggest effects of the theophylline constituent of reproterol to inhibit adenylyl cyclase induced phosphodiesterase activity. The advantageous synergistic effects of reproterol on cAMP-production need to be further explored in trials.

1-Methyl-3-isobutylxanthine↗
PubMed2004

Reliability of non-invasively acquired human genomic DNA as a substrate for real-time PCR-assisted analysis of genetic polymorphisms.

Molecular epidemiological studies require high numbers of participants. The combination of an non-invasive access to human DNA with a rapid genotyping analysis, e.g. by use of LightCycler assisted real-time polymerase chain reaction (PCR), can be helpful in conducting such trials. The aim of our study was to define, for the first time, the use of LightCycler technology in analysis of non-invasively derived DNA. DNA extracted from blood, mouthwash and buccal cytobrush samples from 100 volunteers was analyzed for the genotypes of cytochrome P450 CYP1B1, and glutathione S-transferases GSTT1, GSTM1 and GSTP1. The median amounts of DNA isolated from blood, mouthwash and buccal cytobrush samples were 95, 11 and 8 microg, respectively. While genotyping for CYP1B1 codon 432 polymorphism and GSTP1 codon 105 polymorphism resulted in a complete correspondence for all three modes of sampling, the identification of individuals with null-genotype for GSTT1 or GSTM1 failed in some cases due to atypical courses of the corresponding melting curves, leading to high false-positive rates in the group of non-invasively derived samples. Thus, the results presented here call for caution in using LightCycler assisted real-time PCR in non-invasively collected samples, at least when appropriate control strategies are not implemented.

Adult↗
PubMed2004

[Actinomycosis].

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Actinomycosis, Cervicofacial↗