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- Pedersen, T.R., et al.
(författare)
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Follow-up study of patients randomized in The Scandinavian Simvastatin Survival Study (4S) of cholesterol lowering
- 2000
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Ingår i: American Journal of Cardiology. - 0002-9149 .- 1879-1913. ; 86:3, s. 257-262
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Tidskriftsartikel (refereegranskat)abstract
- The Scandinavian Simvastatin Survival Study (4S) and other randomized clinical trials have demonstrated that cholesterol-lowering treatment with statins improves prognosis in patients with coronary atherosclerosis compared with placebo. The effect of therapy with statins beyond the typical 5 to 6 years' duration of the trials, in particular regarding the risk of cancer, has not been investigated. This study examines the long-term effects of simvastatin for up to 8 years on cause-specific mortality in patients with coronary heart disease (CHD). We performed an observational, government registry-based study of mortality in the groups originally randomized to simvastatin or placebo in the 4S over an additional 2-year follow-up period, so that the median total follow-up period was 7.4 years (range 6.9 to 8.3 in surviving patients). Randomization took place at outpatient clinics at 94 clinical centers in Denmark, Finland, Iceland, Norway, and Sweden from 1988 to 1989. Of 4,444 patients with CHD, 2,223 and 2,221 were randomized to treatment with placebo or simvastatin therapy, respectively. Patients received treatment with simvastatin, starting at 20 mg/day, with titration to 40 mg/day at 12 or 24 weeks if total cholesterol was >5.2 mmol/L (200 mg/dl), or placebo. After the double-blind period, most patients in both treatment groups received simvastatin as open-label prescription. Of the 1,967 patients originally treated with placebo and surviving the double-blind period, 97 (4.9%) died during the following 2 years. In the group randomized to simvastatin the corresponding number was 74 of the 2,039 survivors (3.6%). Adding these deaths to those occurring during the original trial, the total was 353 (15.9%) and 256 (11.5%) deaths in the groups originally randomized to placebo and simvastatin, respectively. The relative risk was 0.70 (95% confidence interval 0.60 to 0.82, p = 0.00002). The total number of cancer deaths was 68 (3.1%) in the placebo group and 52 (2.3%) in the simvastatin group (relative risk 0.73, 95% confidence interval 0.51 to 0.05, p = 0.087), and the numbers of noncardiovascular and other deaths were similar in both groups. We therefore conclude that treatment with simvastatin for up to 8 years in patients with CHD is safe and yields continued survival benefit. Copyright (C) 2000 Excerpta Medica Inc.
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| 3. |
- Idla, K., et al.
(författare)
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Good adhesion between chemically oxidized titanium and electrochemically deposited polypyrrole
- 2000
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Ingår i: Electrochimica Acta. - 0013-4686 .- 1873-3859. ; 45:13, s. 2121-2130
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Tidskriftsartikel (refereegranskat)abstract
- A method for producing extremely adhesive polypyrrole (Ppy) films is described. The electrochemical synthesis of Ppy on thin chemically pre-oxidized Ti layers produces a mechanically strong, shiny polymer film with extremely good adhesion. Adhesion of Ppy films on Ti metal without chemical pre-oxidation is very weak. Two multilayer systems are described with Ppy as an electrochemically active layer, chemically oxidized Ti (TixOy) as a thin adhesive layer, and either a Si-wafer or Al foil as a substrate. Ppy films survive more than 6000 reduction-oxidation cycles in aqueous electrolyte without delamination. The possible mechanisms of enhanced adhesion are discussed. Those are: (1) increased adhesion due to changes in the chemical composition and surface structure of the pre-oxidized Ti, (2) the possibility of the chemical oxidation of pyrrole on the metal surface in addition to the electrochemical polymerization, (3) the adsorption of pyrrole molecules onto pre-oxidized Ti surface by interaction with Ti hydroxides on surface, and (4) the simultaneous growth of TixOy and Ppy.
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| 6. |
- Strandberg, K, et al.
(författare)
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A new method to measure plasma levels of activated protein C in complex with protein C inhibitor in patients with acute coronary syndromes
- 2001
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 12:7, s. 503-510
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Tidskriftsartikel (refereegranskat)abstract
- Our newly devised immunofluorometric sandwich assay for measuring plasma concentrations of activated protein C (APC) in complex with protein C inhibitor (PCI) was compared with testing for conventional markers of myocardial damage CKMB (creatine kinase MB), TNI (troponin I) and hypercoagulability (D-dimer, TAT) in 76 patients with suspected myocardial infarction (MI). APC-PCI complex levels in samples drawn on admission did not correlate with CKMB in the simultaneously drawn sample but correlated closely with maximal CKMB, which reflects MI size (r = 0.52). The areas under the receiver operating characteristics (ROC) curves calculated for the APC-PCI complex results obtained upon admission did not differ significantly from the corresponding values for CKMB, TNI or TAT. Our results show that in patients at risk for MI, the APC-PCI concentration is a sensitive and independent marker that can identify a subgroup of MI patients with normal CKMB but an increased APC-PCI level upon admission. It remains to be determined whether these patients would benefit from early intensive anticoagulant treatment.
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| 7. |
- Söderlind, Eskil, et al.
(författare)
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Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries
- 2000
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 18:8, s. 852-856
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Tidskriftsartikel (refereegranskat)abstract
- We constructed a single-chain Fv antibody library that permits human complementarity-determining region (CDR) gene fragments of any germline to be incorporated combinatorially into the appropriate positions of the variable-region frameworks VH-DP47 and VL-DPL3. A library of 2 x 109 independent transformants was screened against haptens, peptides, carbohydrates, and proteins, and the selected antibody fragments exhibited dissociation constants in the subnanomolar range. The antibody genes in this library were built on a single master framework into which diverse CDRs were allowed to recombine. These CDRs were sampled from in vivo-processed gene sequences, thus potentially optimizing the levels of correctly folded and functional molecules, and resulting in a molecule exhibiting a lower computed immunogenicity compared to naive immunoglobulins. Using the modularized assembly process to incorporate foreign sequences into an immunoglobulin scaffold, it is possible to vary as many as six CDRs at the same time, creating genetic and funcfional variation in antibody molecules.
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