Biomedical subjects

F Hudig

Publications and source records attributed to F Hudig.

5 recordsLinked to original sources

PubMed2005

Exclusion of venous thromboembolism: evaluation of D-Dimer PLUS for the quantitative determination of D-dimer.

The objective of this study was to evaluate if D-Dimer PLUS (Dade Behring, USA), a rapid fully automated assay, could be used as an initial screening test in the diagnosis of venous thromboembolism (VTE). Samples from 274 consecutive symptomatic patients with suspected pulmonary embolism (n=229; 79% outpatients, 21% inpatients), deep venous thrombosis (n=37; 84% outpatients, 16% inpatients) or suspected for both complications (n=8) were tested with this D-dimer assay with a Sysmex CA-1500 Coagulation Analyzer. Clinical probability for pulmonary embolism (PE) or deep venous thrombosis (DVT) was staged according to a pretest risk score proposed by Wells. Final diagnosis of PE and/or DVT was established by spiral-computed tomography of the pulmonary arteries or compression ultrasonography, respectively. PE was diagnosed in 13.5% of the patients, whereas DVT was confirmed in 17.7% of the patients. The optimal cut-off value for exclusion of venous thromboembolism was 130 mug/l, and sensitivity, specificity and negative predictive value (NPV) were 95.0% (95% CI: 92.4-97.6), 30.4% (95% CI: 25.0-35.8) and 97.2% (95% CI: 95.2-99.2), respectively. In fact, two patient with PE were missed using D-Dimer PLUS; both cases were outpatients. In conclusion, this assay appears to be safe when implemented in an algorithm based on clinical assessment, D-dimer concentration, and radiological diagnostic techniques to stratify the risk for PE or DVT. However, higher sensitivities and negative predictive values were claimed in the scarce published reports for the D-Dimer PLUS assay than found in this study.

Cohort Studies↗

PubMed1998

Effects of triiodothyronine and amiodarone on the promoter of the human LDL receptor gene.

Treatment of patients with amiodarone, a potent anti arrhythmic drug, increases plasma LDL cholesterol levels, similar to that seen during hypothyroidism. This increase is the result of a decreased expression of the hepatic LDL receptor gene. We investigated the effects of thyroid hormone, amiodarone and desethylamiodarone on the first 687 bp upstream of the first ATG of the human LDL receptor gene by co-transfection with TRbeta1 into HepG2 cells. Promoter activity showed a dose-dependent increase upon addition of thyroid hormone up to a maximum of 600% at 10(-6) M T3. Using 5'-deletions it was found that a functional TRE(s) is present between -687 bp and -160 bp upstream of the ATG of the LDL receptor gene. Amiodarone and desethylamiodarone at 10(-6) M reduced basal LDL receptor promoter activity further then with the TRbeta1 alone (to 30% vs. 50% respectively, p<0.01) but interestingly in combination with T3 these compunds show a synergistic effect on promoter activity (to 225% T3 alone vs. 380% respectively, p<0.01).

Amiodarone↗

PubMed1998

Amiodarone decreases gene expression of low-density lipoprotein receptor at both the mRNA and the protein level.

Amiodarone, a potent antiarrhythmic drug, decreases plasma and tissue triiodothyronine (T3) and increases plasma cholesterol levels, resembling changes seen during hypothyroidism. The increase of serum cholesterol during amiodarone medication is associated with a decreased expression of the hepatic low-density lipoprotein (LDL) receptor mRNA. To further elucidate the mechanism of amiodarone-induced hypercholesterolemia, we investigated whether the decreased mRNA levels are the result of decreased transcription or increased degradation or both, and whether protein expression is decreased accordingly. Relative to pair-fed controls, amiodarone treatment increased plasma cholesterol by 69% and decreased expression of the mRNA encoding for the hepatic LDL receptor by 45%. To study this decrease in mRNA, we performed a run-on assay, from which it appears that amiodarone acts by decreasing LDL receptor mRNA expression 2.5-fold at the transcriptional level. The decay rate of liver LDL receptor mRNA, measured at different time points after injecting actinomycin D, was not different between amiodarone-treated and control animals (116+/-32 minutes and 84+/-10 minutes, P=.44). Hepatocytes in primary culture isolated from amiodarone-treated and control animals were used to determine specific binding of [125I]-LDL to hepatic LDL receptors. Amiodarone decreased specific LDL binding and Scatchard analysis demonstrated that amiodarone treatment reduced the number of LDL receptors by 69%, without affecting the dissociation constant (Kd). In conclusion, amiodarone-induced hypercholesterolemia can be explained by decreased transcription of the LDL receptor gene, resulting in lower mRNA and protein levels.

Amiodarone↗

PubMed1997

Tri-iodothyronine prevents the amiodarone-induced decrease in the expression of the liver low-density lipoprotein receptor gene.

Treatment with amiodarone, a potent antiarrhythmic drug, is associated with a dose-dependent increase in plasma cholesterol resulting from a decreased number of liver low-density lipoprotein (LDL) receptors. Similar changes occur in hypothyroidism, and it has been suggested that amiodarone acts via induction of a local 'hypothyroid-like' state in extrathyroidal tissues. The present study was designed to evaluate whether exogenous tri-iodothyronine (T3) could prevent the effects of amiodarone on LDL cholesterol. Rats were treated for 14 days with water, amiodarone 10 mg/100 g body weight (BW), or amiodarone and 2.5, 5 or 10 micrograms T3/100 g BW respectively. Relative to controls, amiodarone increased plasma LDL cholesterol by 31% and decreased liver LDL receptor mRNA by 56% and protein by 45%; liver T3 content was reduced by 21%. Addition of T3 to the treatment with amiodarone dose-dependently reversed all these changes, with a return to control values of plasma cholesterol and the number of liver LDL receptors, although LDL receptor mRNA remained slightly lower. Treatment of rats for 14 days with T3 alone (5 micrograms/100 g BW) decreased plasma LDL cholesterol by 19% and increased liver LDL receptor mRNA by 41%. In conclusion, T3 prevents the amiodarone-induced changes in plasma LDL cholesterol and liver LDL receptor gene expression. These findings suggest that the inhibitory effect of amiodarone on LDL receptor gene expression is mediated by T3-dependent pathways.

Amiodarone↗

PubMed1994

Amiodarone-induced hypercholesterolemia is associated with a decrease in liver LDL receptor mRNA.

Amiodarone decreases plasma and tissue triiodothyronine (T3) and increases plasma cholesterol levels resembling changes seen during hypothyroidism. To elucidate the mechanism of amiodarone-induced hypercholesterolemia we investigated gene expression of three key proteins in cholesterol metabolism (cholesterol 7 alpha-hydroxylase, LDL receptor, HMG-CoA reductase) in livers of rats. Animals were treated with amiodarone or propylthiouracil (to induce mild hypothyroidism). The LDL receptor mRNA was downregulated (approximately 50%) in both amiodarone-treated and hypothyroid animals, while the other mRNA remained unchanged after 14-day treatment. The results suggest that amiodarone-induced hypercholesterolemia is associated with decreased LDL receptor mRNA levels.

Amiodarone↗