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Biomedical subjects

Esther B Bachli

Publications and source records attributed to Esther B Bachli.

11 recordsLinked to original sources
PubMed2006

A single dose of oral vitamin K effectively reverses oral anticoagulation with phenprocoumon during heart catheterisation.

QUESTION UNDER STUDY: To investigate the effectiveness of a single adjusted dose of oral vitamin K to temporarily reverse oral anticoagulation with phenprocoumon (Marcoumar) for heart catheterisation. METHODS: Patients under stable oral anticoagulation with phenprocoumon routinely scheduled for heart catheterizstion were given a single adjusted dose of oral vitamin K a day prior to the intervention. The customary anticoagulation scheme was kept unchanged with the exception of taking the double usual dose of phenprocoumon the evening after the intervention. The primary outcome was the achieved international normalised ratio (INR) immediately before the intervention. Secondary outcomes were the INR after one and four weeks, changes in phenprocoumon and coagulation factors II and VII and adverse events. RESULTS: 38 patients at a median age of 71 (63-74) years scheduled for heart catheterisation were included. The median INR changed from 2.2 (1.9-2.6) the day before to 1.5 (1.4-1.7) immediately before the intervention. An INR < or =1.5 respectively < or =1.8 was achieved in 61% and 95% of the patients. The INR values after one respectively four weeks were comparable to preintervention values. No thromboembolic or bleeding adverse events occurred during the study. CONCLUSION: A single adjusted oral dose of vitamin K given a day prior to heart catheterisation combined with a doubled phenprocoumon dose on the procedure day seems to be an easy applicable, safe and effective way to temporary reverse oral anticoagulation with phenprocoumon.

Administration, Oral↗
PubMed2004

Gene expression profiling of inflamed human endothelial cells and influence of activated protein C.

BACKGROUND: During systemic inflammation, activation of vascular endothelium by proinflammatory cytokines leads to hypotension, microvascular thrombosis, and organ damage. Recent data suggest a link between coagulation and inflammation through the activated protein C (APC) pathway. We studied gene expression profiles in human coronary artery endothelial cells (HCAECs) exposed to proinflammatory stimuli and the influence of APC on expression of candidate genes regulated by these stimuli. METHODS AND RESULTS: HCAECs were stimulated with interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha. In gene expression profiling, 400 of 8400 genes were regulated >2-fold. Verification of selected candidate genes was achieved by measuring expression of mRNA species by real-time polymerase chain reaction, cytokine secretion by ELISA, and metabolites of tetrahydrobiopterin (BH4) biosynthesis by high-performance liquid chromatography. BH4 synthesis, interleukin-6, interleukin-8, monocyte chemotactic protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were downregulated by APC at the transcriptional and protein level. Endothelial nitric oxide synthase, endothelial adhesion molecule, and vascular cell adhesion molecule-1 were not affected by APC. Activities of transcription factors c-Fos, FosB, and c-Rel were inhibited by APC in inflamed HCAECs. CONCLUSIONS: Our study revealed a novel antiinflammatory mechanism of APC-dependent gene regulation in HCAECs since c-Fos-dependent induction of MCP-1 and ICAM-1 was suppressed. APC downregulates expression and activity of genes related to inflammation, most pronounced under intermediate or mild inflammatory conditions.

Biopterins↗
PubMed2004

Functional tetrahydrobiopterin synthesis in human platelets.

BACKGROUND: Previous studies have provided evidence for the importance of platelet-derived nitric oxide (NO) for the regulation of hemostasis. Tetrahydrobiopterin (BH4) is an essential cofactor and regulator of NO synthase activity in the vasculature; however, it is as yet unknown whether platelets dispose over a functional BH4 synthesis. METHODS AND RESULTS: We quantified mRNA expression of genes involved in BH4 synthesis, measured enzymatic activities, and determined intraplatelet levels of pteridines in platelets from healthy volunteers and from patients treated for prolonged periods of time with glucocorticoids. Freshly isolated platelets from healthy volunteers show functional BH4 synthesis, as evidenced by the presence of mRNA species and enzymatic activity of GTP cyclohydrolase I (GTPCH), 6-pyruvoyl tetrahydropterin synthase, and sepiapterin reductase. Biopterin was the major intraplatelet pteridine, whereas no neopterin was found. mRNA expression and enzymatic activity of GTPCH were undetectably low in platelets that had been stored for 5 days, and no pteridines were found in these platelets. Freshly isolated platelets from patients treated with glucocorticoids had decreased mRNA expression and activity of GTPCH compared with platelets from healthy volunteers. CONCLUSIONS: Human platelets dispose over a functional de novo BH4 synthesis. Furthermore, our results indicate the potential of external factors, eg, prolonged storage or glucocorticoid therapy, to significantly affect BH4 synthesis within platelets. Together, these findings offer new insights into the biology and pathobiology of platelet function in humans.

Adult↗
PubMed2004

Hermansky-Pudlak syndrome type 4 in a patient from Sri Lanka with pulmonary fibrosis.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a platelet storage pool deficiency. Some patients also develop fatal pulmonary fibrosis and some have granulomatous colitis. Six human genes HPS1, ADB3A, HPS3, HPS4, HPS5, and HPS6 have been identified as cause of the six known subtypes of HPS. While there exist nearly 500 Puerto Rican and non-Puerto Rican HPS-1 patients, very few HPS-4 patients have been reported, and most of these have not been described in detail. We now delineate the clinical characteristics of an HPS-4 patient homozygous for a novel HPS-4 mutation, P685delC. The patient, the first individual with HPS reported from Sri Lanka, had severe pulmonary fibrosis, typical of HPS-1 disease, without granulomatous colitis. We conclude that pulmonary fibrosis occurs as part of HPS-4 and that HPS should be considered in all ethnic groups.

Albinism, Oculocutaneous↗
PubMed2003

Morphologic changes and altered gene expression in an epithelioid hemangioendothelioma during a ten-year course of disease.

Epithelioid hemangioendothelioma (EHE) is a rare low-grade malignant vascular neoplasm with unpredictable prognosis. We report on a patient suffering from a vascular neoplasm with primary manifestation in the skeleton and subsequent development of lesions of EHE in the spleen, liver and lung. Based on the assumption that involvement of visceral organs was due to metastatic spread, changes in clinical behavior, morphology, and proliferation index suggest malignant progression of the tumor. Analyzing the expression of genes known to be involved in the pathogenesis of vascular tumors, we found that the appearance of less differentiated tumor was paralleled by an accumulation of TP53 and murine double minute-2 (MDM-2) protein, decreased caveolin-1 (CAV-1) expression, and increased vascular endothelial growth factor (VEGF) expression. Mutations of the von-Hippel-Lindau-tumor-suppressor-gene (VHL) were excluded as mechanism of VEGF upregulation. Therefore, we propose that the expression of TP53, MDM-2, CAV-1 and VEGF as a marker of biologic behavior be verified in a larger case study of EHE.

Arabidopsis Proteins↗