Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jan 2008
Multicenter StudyCyclooxygenase polymorphisms and risk of cardiovascular events: the Atherosclerosis Risk in Communities (ARIC) study.
Cyclooxygenase-derived prostaglandins modulate cardiovascular disease risk. We genotyped 2212 Atherosclerosis Risk in Communities study participants (1,023 incident coronary heart disease (CHD) cases; 270 incident ischemic stroke cases; 919 non-cases) with available DNA for polymorphisms in PTGS1 and PTGS2. Using a case-cohort design, associations between genotype and CHD or stroke risk were evaluated using proportional hazards regression. ⋯ However, aspirin utilization appeared to modify the relationship between the PTGS2 G-765C polymorphism and CHD risk (interaction P=0.072). These findings suggest that genetic variation in PTGS1 and PTGS2 may be important risk factors for the development of cardiovascular disease events. Confirmation in independent populations is necessary.
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Clin. Pharmacol. Ther. · Jan 2008
Randomized Controlled TrialEnhanced buprenorphine analgesia with the addition of ultra-low-dose naloxone in healthy subjects.
Animal studies have demonstrated that co-administration of an ultra-low-dose opioid antagonist with an opioid agonist may result in enhanced analgesia. Investigation of this effect in humans has been limited and produced inconsistent findings, with previous reports suggesting that dose ratio may be critical to analgesic potentiation. ⋯ Importantly, this enhanced analgesia occurred without an increase in adverse effects; indeed at some ratios, respiratory depression was attenuated. These findings demonstrate that the addition of ultra-low-dose naloxone can enhance the analgesic effect of buprenorphine in humans without a concurrent increase in side effects.
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Clin. Pharmacol. Ther. · Jan 2008
Emergency contraception: a reasonable personal choice or a destructive societal influence?
A 2003 petition to the US Food and Drug Administration by the manufacturer to move levonorgestrel emergency contraception from prescription status to over-the-counter sale embroiled the Agency in politics and remains controversial in some circles. This essay addresses the current remaining main points of contoversy about the medication and the Agency's decision.
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Clin. Pharmacol. Ther. · Dec 2007
ReviewHeterogeneity in vaccine immune response: the role of immunogenetics and the emerging field of vaccinomics.
Recent advances in the fields of immunology, genetics, molecular biology, bioinformatics, and the Human Genome Project have allowed for the emergence of the field of vaccinomics. Vaccinomics encompasses the fields of immunogenetics and immunogenomics as applied to understanding the mechanisms of heterogeneity in immune responses to vaccines. ⋯ In turn, this data, in concert with new high-throughput technology, inform the immune-response network theory to vaccine response. Such information can be used in the directed and rational development of new vaccines, and this new golden age of vaccinology has been termed "predictive vaccinology", which will predict the likelihood of a vaccine response or an adverse response to a vaccine, the number of doses needed and even whether a vaccine is likely to be of benefit (i.e., is the individual at risk for the outcome for which the vaccine is being administered?).