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Biomedical subjects

S Schellong

Publications and source records attributed to S Schellong.

At least 19 recordsLinked to original sources
PubMed2006

Complete ulcer healing as primary endpoint in studies on critical limb ischemia? A critical reappraisal.

OBJECTIVES: Although complete ulcer healing is the mandatory primary efficacy criterion in current European guidelines for drug trials in critical limb ischemia (CLI), the appropriateness of this endpoint has been questioned for some time. We carried out a systematic review to assess the value of this endpoint in studies on reconstructive measures, considered to be the standard of care for CLI. METHODS: A computerized literature search (1985-2005) was performed to track down clinical studies on endovascular and surgical interventions by using the search terms CLI and ulcer healing and their synonyms. RESULTS: 1,914 papers on revascularization in CLI were identified. Complete ulcer healing was reported in 17 studies (0.9%). Among these, there were no randomized controlled trials, five prospective cohorts on endovascular procedures, and six retrospective cohorts for endovascular and surgical procedures, respectively. If healing rates or time to ulcer healing were available, they differed greatly between the studies without consistent correlation to types of therapy. CONCLUSIONS: In past and current literature, complete ulcer healing is not a consistently reported criterion for success of revascularization in CLI. Thus, its appropriateness for efficacy assessment of drug studies in CLI patients has to be questioned.

Diabetic Angiopathies↗
PubMed2006

Matrix metalloproteinase 2 polymorphisms in a caucasian population with abdominal aortic aneurysm.

BACKGROUND: The formation of sporadic abdominal aortic aneurysm (AAA) is explained by remodeling of the extracellular matrix (ECM) and breakdown of structural components of the vascular wall. Matrix metalloproteinase 2 (MMP2) is one of the principal matrix-degrading proteases and is known to play a major role in the remodeling of the extracellular matrix in arterial vessels. Increased MMP2 expression in the extracellular matrix of the walls of AAAs has been shown in several studies. To investigate the possible impact of genetic variants of the MMP2 gene in the etiology of AAA, we conducted this case-control study. PATIENTS AND METHODS: We analyzed MMP2 single-nucleotide polymorphisms (SNPs) in 51 patients with AAA and 48 controls. Differences in genotype and allele frequencies of identified polymorphisms were determined after sequencing the entire coding region and three selected parts of the promoter. RESULTS: Eighteen polymorphisms were identified, 6 of which are newly described, with 3 located in the introns (c.IVS1+31C>G, c.IVS7-18G>A, c.IVS10+26C>T) and 3 located in the coding region (c.124G>A, c.1368C>T, c.1860C>T). There were no statistically significant differences in genotype or allele frequencies between the two groups. CONCLUSIONS: Our analysis of the entire coding region and three parts of the promoter of the MMP2 gene failed to show an association between genetic polymorphisms and AAA, suggesting that variations in the MMP2 gene do not contribute to the development of AAA.

Aged↗
PubMed2006

The influence of downstream arterial perfusion parameters on doppler pulsatility index and resistance index in an in-vitro perfusion model.

BACKGROUND: To investigate in vitro how downstream perfusion parameters influence pulsatility index (PI), resistance index (RI) and their constituting Doppler velocities. MATERIALS AND METHODS: We analyzed the influence of resistance, compliance, reflection coefficient and input impedance on PI and RI in an in-vitro model of arterial flow. RESULTS: The nominators of PI and RI were determined by resistance. The numerators were determined by compliance and by the reflection coefficient. There were close relationships of PI and RI with resistance under the condition of constant compliance, but not when compliance was variable. CONCLUSION: PI and RI consist of velocity terms which are independently influenced by different parameters of impedance: compliance, reflection coefficient and resistance. These findings explain the contradictory results reported for the relationship between the indices and peripheral resistance in studies where compliance and reflection effects were not considered.

Animals↗
PubMed2005

[Management of pulmonary embolism].

Venous thromboembolism is often triggered by transient episodes of increased risk but may occur spontaneously in patients with permanently increased risk. Pulmonary embolism may cause impairment of respiratory and circulatory function which can vary in severity from silent to catastrophic. The diagnosis can be feasibly established by detecting vein thrombosis. If this approach fails, demonstration of pulmonary emboli by lung scans becomes necessary to establish the diagnosis. A D-dimer-test can select patients in whom imaging of pulmonary perfusion is required. Immediate therapeutic anticoagulation with heparins is mandatory in confirmed thromboembolism, and is followed by a vitamin K antagonist. In the initial work-up, patients also have to be evaluated for systemic thrombolytic therapy by hemodynamic parameters and echocardiography. In a triggered episode of venous thromboembolism, duration of anticoagulation is confined to several months while spontaneous or recurrent events require prolonged or indefinite treatment.

Anticoagulants↗
PubMed2005

[Fibrinolytic therapy].

Fibrinolytic therapy still is a keystone in the therapeutic approach of acute occlusion in different vascular regions. However, before starting fibrinolytic therapy an evidence-based risk assessment is necessary. This article presents the most common fibrinolytic agents as well as evidences and recommendations for fibrinolytic therapy of different vascular regions.

Fibrinolytic Agents↗
PubMed2004

Microcirculation and tolerability following i.v. infusion of PGE1 and iloprost: a randomized cross-over study in patients with critical limb ischemia.

In a randomized cross-over study, the effect of PGE(1) and iloprost on microcirculation as well as the tolerability was investigated in 36 patients with peripheral arterial occlusive disease stage III and IV according to Fontaine. Patients received PGE(1) and iloprost by single 3-h i.v. infusions on two different days at doses recommended by the manufacturers or in previous studies (PGE(1): first hour 20 microg, next 2h 30 microg each. Iloprost: first hour 0.5 ng/kg/min, next 2h 1.0 ng/kg/min). Transcutaneous oxygen pressure (tcPO(2)) values increased much more with PGE(1). Median tcPO(2) increase over baseline 30 min after the end of infusion was 9 and 2 mmHg for PGE(1) and iloprost, respectively, corresponding to median AUC differences from baseline of 1050 and 210 min mmHg. Because of its exploratory character, the study was not powered to test for significance. Adverse effects occurred in 19.4% (PGE(1)) and 30.6% (iloprost) of patients. Dose reduction was required in 3 patients receiving iloprost (hypotension, nausea, irritation of the infused vein), and in none receiving PGE(1).

Aged↗
PubMed2004

[Home treatment for deep vein thrombosis: pros and cons].

There is sound evidence, that low molecular weight heparin (LMWH) administered subcutaneously is at least as effective and safe as an i.v. infusion of unfractionated heparin. Thus, with LMWH out-patient treatment of deep vein thrombosis (DVT) becomes feasible. According to the current guidelines, an objective diagnosis of DVT is required before the anticoagulation with heparin is initiated. Close monitoring is also required during the subsequent initiation of treatment with vitamin K antagonist. Contraindications and comorbid conditions need to be identified and may necessitate hospital treatment. A checklist may assist in the decision for or against out-patient treatment, but an individual assessment for the individual patient is always a requisite.

Anticoagulants↗
PubMed2003

[Interstitial Nd:YAG laser therapy. Color-Doppler imaging (CDI)-guided laser therapy of hemangiomas and vascular malformations].

BACKGROUND AND OBJECTIVE: Ultrasound-(US-) guided Nd:YAG laser therapy has been reported to be promising among different other options for treatment of hemangiomas and vascular malformations. The concept of CDI-guided interstitial laser therapy is therefore a further development based on the above mentioned therapeutic regime. PATIENTS AND METHODS: We examined 55 patients suffering from vascular lesions of different localization and extent pre-, intra-, and post-operatively using color-Doppler imaging (CDI). All vascular lesions were classified due to their vascularization pattern. As accurate diagnosis was imperative we decided on possible laser treatment depending on the CDI-classification. RESULTS: Intra-operative use of CDI rendered possible fiber-guidance by sonographic navigation and therefore precise treatment of aberrant vessels and well-perfused tumor areas. In 34 cases (62%) we observed complete, in 21 cases (38%) partial regression of vascular lesions. CDI allowed post-operative proof of diminution of tumor vascularization in all cases. CONCLUSIONS: CDI-guided interstitial Nd:YAG laser therapy is a minimally-invasive technique which allows replacement of conventional surgical procedures while achieving good cosmetic and functional results.CDI broadens the therapeutic possibilities in contrast to the former therapeutic concept of US-guided laser therapy due to pre-, intra and post-operative utilization of this imaging technique while significantly diminishing the intra-operative risk for the patient.

Adolescent↗
PubMed2003

[Early and loud].

Explore the source record for details and available documents.

Anticoagulants↗
PubMed2003

Polymorphisms in the TAFI gene and the risk of venous thrombosis.

Thrombin-activable fibrinolysis inhibitor (TAFI) is a recently described inhibitor of fibrinolysis. The aim of this study was to estimate the risk of deep venous thrombosis (DVT) caused by the polymorphisms in the TAFI gene in relation to polymorphisms of the other fibrinolytic variables such as PAI-844A>G and t-PA-7,351C>T. This study includes 130 patients with DVT and 130 age- and sex-matched healthy controls. Our results showed no association of the investigated "TAFI-increasing" alleles TAFI 505A (Thr147) and TAFI+1542C with the risk of venous thrombosis. However the adjustment for age, sex, factor V Leiden, PAI-844A allele and t-PA-7,351T allele indicates a tendency to a moderately increased thrombotic risk of TAFI+1542GG carriers (low TAFI level).

Chromosomal Proteins, Non-Histone↗
PubMed2001

Anticoagulation: the present and future.

Thrombin is a central bioregulator of coagulation and is therefore a key target in the therapeutic prevention and treatment of thromboembolic disorders, including deep vein thrombosis and pulmonary embolism. The current mainstays of anticoagulation treatment are heparins, which are indirect thrombin inhibitors, and coumarins, such as warfarin, which modulate the synthesis of vitamin K-dependent proteins. Although efficacious and widely used, heparins and coumarins have limitations because their pharmacokinetics and anticoagulant effects are unpredictable, with the risk of bleeding and other complications resulting in the need for close monitoring with their use. Low-molecular-weight heparins (LMWHs) provide a more predictable anticoagulant response, but their use is limited by the need for subcutaneous administration. In addition, discontinuation of heparin treatment can result in a thrombotic rebound due to the inability of these compounds to inhibit clot-bound thrombin. Direct thrombin inhibitors (DTI) are able to target both free and clot-bound thrombin. The first to be used was hirudin, but DTIs with lower molecular weights, such as DuP 714, PPACK, and efegatran, have subsequently been developed, and these agents are better able to inhibit clot-bound thrombin and the thrombotic processes that take place at sites of arterial damage. Such compounds inhibit thrombin by covalently binding to it, but this can result in toxicity and nonspecific binding. The development of reversible noncovalent DTIs, such as inogatran and melagatran, has resulted in safer, more specific and predictable anticoagulant treatment. Oral DTIs, such as ximelagatran, are set to provide a further breakthrough in the prophylaxis and treatment of thrombosis.

Administration, Oral↗
PubMed2000

Frequency of polymorphisms in the B-domain of factor V gene in APC-resistant patients.

In this study we investigated a group of patients in whom a resistance to APC (activated protein C) was found but no Leiden mutation existed in the presence of missense mutations in the first 1200 bp of the Exon 13 (B-domain) in the factor V (FV) gene. The determination of the APC response was performed using the Immunochrom(R) APC response Test Kit. The mutations were determined by temperature gradient gel electrophoresis and DNA sequencing. In the APC-resistant patients without the FV Leiden, we found 4 silent mutations (2298C>T, 2325T>C, 2379A>G, 2391A>G) and 4 missense mutations (2540A>C, 2663A>G, 2684A>G, 2863A>G), which code for the amino acids N789T (GenBank Accession # AF119360), K830R, H837R, and K897E. In all of the patients and controls, the polymorphisms at nucleotide positions 2391, 2663, 2684, and 2863 appeared to be associated. In the major allele all bases are A (A allele) and in the minor allele are G (G allele). A significantly lower G allele frequency was observable in the patient group than in the control group (0.14 vs. 0.31; p<0.05). The frequency of the 2540C allele, which is associated with the 2379G and the 4070G allele (non-Leiden!), did not differ significantly between the patient and the control groups. We suggest that the G allele, which is not associated with the FV Leiden mutation, as well as the [2379G; 2540C; 4070G] allele have no influence on the APC cofactor function itself, or only subtly as determined in the test systems used.

Activated Protein C Resistance↗
PubMed2000

Decreased plasma concentrations of L-hydroxy-arginine as a marker of reduced NO formation in patients with combined cardiovascular risk factors.

Patients with metabolic syndrome represent a group with extensive cardiovascular risk factors for the development of atherosclerosis, which may be preceded by an impairment of endothelial function. Endothelial dysfunction is characterized by a reduced availability of bioactive nitric oxide, the principal mediator of endothelium-dependent vasodilation. In the present study we assessed NO synthesis in vivo by measuring the NO-related amino acids L-arginine and L-citrulline and in particular the stable intermediate compound N(omega)-hydroxy-L-arginine (L-NHA) in patients with metabolic syndrome by using high-performance liquid chromatography (HPLC) analysis. As a prerequisite to our study, we measured the amino acid concentrations in 31 healthy volunteers to investigate gender and age differences. To prove whether blood drawn from peripheral veins reflects plasma concentrations of the whole vessel system, several blood samples from different regions were obtained from patients undergoing elective left and right heart catheterization. In the latter group, no significant differences were noted among the plasma concentrations between the different sample sites. In healthy volunteers, there were no significant differences in plasma concentrations of any one specific amino acid between males and females or age groups. The main finding of the study is that the intermediate product of NO synthesis, L-NHA, is significantly reduced in the plasma samples of patients with a metabolic syndrome as compared with samples from healthy control subjects. The plasma concentrations of the NO precursor L-arginine and the end product of NO synthesis, L-citrulline, were unchanged. In conclusion, our results suggest that plasma levels of L-NHA are independent of age and gender and are not different at various locations within the vascular system. In a group of patients at high risk for the development of atherosclerosis, we found reduced plasma concentrations of L-NHA, either caused by a decreased endothelial NO synthase activity or caused by an increased breakdown of L-NHA by pathways independent of NO synthase, resulting in a reduced availability of L-NHA for NO synthesis.

Adult↗
PubMed2000

Method-dependent influence of certain polymorphisms in the factor V B-domain on the response to activated protein C.

The factor V (FV) B-domain is extremely important to the cofactor function of native FV for activated protein C (APC) in the inactivation of factor VIII (FVIII). In a previous study, we found that in the B-domain coding portion of DNA, the polymorphisms at nucleotide positions 2391, 2663, 2684, and 2863 were associated. In the major allele, all bases are A (A allele) and those in the minor allele are G (G allele). This study concerns itself with the question of whether or not there are differences in the APC response between the A allele and the G allele in plasma samples from persons without the FV Leiden. The APC ratios of homozygous carriers of the major A allele and the minor G allele do not differentiate themselves in classical activated partial thromboplastin time-based assays. In contrast, a test based on the deactivation of FVIII in the tenase complex in homozygous carriers of the minor G allele showed significantly lower APC ratios (P = 0.001) in comparison with the major A allele. The results of the investigation after modification of the test indicate that mutative changes in the B-domain apparently influence the interaction among phospholipids, APC, FV, and protein S. An increase in FVIII through the introduction of the FVIII concentrate Kogenate to the plasma samples was associated with a drop in the APC ratios of both genotypes. After defining 59 age- and sex-based matched pairs without the FV Leiden, the observed frequency of the minor G allele was higher in the non-thrombotic group (33.0%) than in the thrombotic group (22.8%). However, the difference did not reach the level of significance (odds ratio, 0.53; 95% confidence interval, 0.26-1.12). It does, nevertheless, appear possible that a homozygous condition for the minor allele in combination with a defect known to be associated with thrombophilia represents an additional thrombogenetic risk factor.

Activated Protein C Resistance↗
PubMed2000

Low molecular weight heparin: a possible cause for higher protein S activity than free protein S concentration.

Different assays for the assessment of protein S (PS) functional activity are commercially available. We were able to show that, considering the influence of factors known in respect of PS, good agreement can be reached between the results of the determination of free PS as obtained using an immunoassay with monoclonal antibodies and the determination of PS activity as obtained using a test based on activated factor X (factor Xa). However, values of PS activity higher than free PS concentration were obtained in plasma samples taken from patients undergoing therapy with low molecular weight (LMW) heparin. An in vitro incubation of plasma samples with LMW heparin in varying concentrations led, in every case, to an increase of clotting times and thus to an increase of PS activity. In all investigations, the ratios of clotting time with heparin to that without heparin were higher in plasma samples containing PS than in PS-deficient plasma. This result was independent of the use of commercially deficient plasma or the blocking of PS in reference plasma by addition of polyclonal PS antibodies. Obviously, heparin blockers in commercially available assays only neutralize the effect of conventional heparin, and the prolongation of the clotting time is mainly caused by the inhibition of factor Xa by LMW heparin. The reason for the stronger effect in plasma containing PS than in the same plasma after the blocking of PS with polyclonal antibodies as well as in PS-deficient plasma is unclear. Due to the unrecognizable influence of LMW heparin on global clotting assays, the assessment of PS activity values without clear documentation of the application of LMW heparin can lead to improper diagnoses.

Anticoagulants↗