There is growing consensus on the potential use of pharmacogenetics in clinical practice, and hopes have been expressed for application to the improvement of global health. However, two major challenges may lead to widening the "biotechnological gap" between the developing and the industrial world; first the unaffordability of some current technologies for poorer countries, and second the necessity of analyzing all described alleles for every clinical case due to the inability to predict the ethnic group of a given patient. Because of its role in the metabolism of a number of drugs, cytochrome P450 2D6 (CYP2D6) is an excellent candidate for use in the optimization of drug therapy. CYP2D6 is a highly polymorphic gene locus with more than 50 variant alleles, and subjects can be classified as poor metabolizers (PM), extensive metabolizers (EM), or ultrarapid metabolizers (UM) of a given CYP2D6 substrate. Several strategies and methods for CYP2D6 genotyping exist. Some, however, are expensive and laborious. The aim of this study was to design a PCR-based genotyping methodology to allow rapid, straightforward, and inexpensive identification of 90%-95% of CYP2D6 PM or UM genotypes for routine clinical use, independent of the individual's ethnic group. CYP2D6 is amplified in initial extra long PCRs (XL-PCRs), which subsequently undergo fragment-length polymorphism analysis for the determination of carriers of CYP2D6 allelic variants. The same XL-PCRs are also used for the determination of CYP2D6 multiplication and 2D6*5 allele (abolished activity). The application of this new strategy for the detection of CYP2D6 mutated alleles and multiplications to routine clinical analysis will enable the PM and UM phenotypes to be predicted and identified at a reasonable cost in a large number of individuals at most locations.

Breast cancer (BC) is a major public health problem internationally. Although illness survival rates have improved, patients usually suffer multiple symptoms, both physical and psychological, which can affect their quality of life (QoL). The main aim of this study was to evaluate depressive symptoms, anxiety and the QoL of people with BC. An observational, cross-sectional study was carried out at Badajoz University Hospital (Spain). A total of 200 women with BC were included. EORTC QLQ-C30 and QLQ-BR23 questionnaires were used to assess QoL. Patients were screened for depressive symptoms using the Beck Depression Inventory (BDI) and for state anxiety and trait anxiety using the State Anxiety Inventory (STAI). Thirty-eight percent of the patients in the sample had moderate to severe anxiety, which was related to the time of diagnosis, advanced stage of illness and surgical treatment. We found that 28% of patients had depressive symptoms, related mainly with time of diagnosis, adjuvant therapy and number of cycles of chemotherapy (CT). Patients with the longest time since diagnosis, in stage III, and in treatment with CT, especially those with the greatest number of cycles, had the worst scores in QoL. We found a positive association between depressive symptoms and anxiety with QoL in patients with BC.

In the recent years it has been increasingly recognized that pharmacogenetical factors play an important role in the drug treatment. These factors may influence the appearance of side-effects and drug interactions due to interindividual differences in the activity of metabolizing enzymes. Risperidone in humans is mainly metabolized to 9-hydroxyrisperidone by the polymorphic cytochrome enzyme P450 2D6 (CYP2D6). Plasma concentrations of risperidone and 9-hydroxyrisperidone show large interindividual variability, which may be partly related to the activity of the CYP2D6 enzyme. Around seven percent of Caucasians have a genetically inherited impaired activity of the CYP2D6 enzyme. Debrisoquine metabolic ratio (a marker of CYP2D6 activity) and the number of CYP2D6 active genes have been related to risperidone plasma concentrations among patients during steadystate conditions. A large number drugs have been described to be metabolized by CYP2D6, and it is therefore important to evaluate the clinical significance of the impaired metabolism and possible drug interactions on the enzyme. Since risperidone / 9-hydroxyrisperidone ratio strongly correlates with CYP2D6 enzyme activity and the number of CYP2D6 active genes, thus it might be an useful tool in clinical practice to estimate the possible risk of drug interactions due to impaired CYP2D6 enzyme activity. CYP3A4 is the most abundant drug metabolizing enzyme in humans, and in vitro and in vivo results suggest also a role for the enzyme in risperidone metabolism. The consideration of the implication of cytochrome P450 enzymes in risperidone metabolism may help to individualize dose schemes in order to avoid interactions and potentially dangerous side-effects, such us QTc interval lengthening among patients with cardiac risk factors.

Monoclonal antibodies constitute important and useful tools in clinical practice and biotechnology for diagnosing and treating infectious, inflammatory, immunological and neoplastic diseases. This article reviews evidence on the different acute adverse effects of monoclonal antibodies, specifically infusion-related reactions (IRRs), and on the measures that should be taken before and during crises. A literature search using key terms relating to IRRs produced by monoclonal antibodies was undertaken to generate a comprehensive narrative review of the information available. Immunomodulatory monoclonal antibodies may produce IRRs and hypersensitivity-related reactions. Strategies to avoid or minimize the appearance of IRRs depend on the monoclonal antibody and type of patient and reaction (pre-medication, slowing infusion rates, infusion interruption or desensitization, etc.). Considering the great number of available monoclonal antibodies in current practice and those which will soon be authorized, it is mandatory to have clear guidelines that can give support to practitioners and nurses to help them respond quickly and safely to the different IRRs related to the use of these therapeutic drugs.