1,721,624 research outputs found
Pharmacogenetics: Implementing personalized medicine
No full textPharmacogenetics and pharmacogenomics have been widely recognized as fundamental steps toward personalized medicine. They deal with genetically determined variants in how individuals respond to drugs, and hold the promise to revolutionize drug therapy by tailoring it according to individual genotypes. The clinical need for novel approaches to improve drug therapy derives from the high rate of adverse reactions to drugs and their lack of efficacy in many individuals that may be predicted by pharmacogenetic testing. Significant advances in pharmacogenetic research have been made since inherited differences in response to drugs such as isoniazid and succinylcholine were explored in the 1950s. The clinical utility and applications of pharmacogenetics and pharmacogenomics are at present particularly evident in some therapeutic areas (anticancer, psycotrophic, and anticoagulant drugs). Recent evidence derived from several studies includes screening for thiopurine methyl transferase or uridine 5′-diphospho-glucuronosyl-transferase 1A1 gene polymorphisms to prevent mercaptopurine and azathioprine or irinotecan induced myelo-suppression, respectively. Also there is a large body of information concerning cytochrome P450 gene polymorphisms and their relationship to drug toxicity and response. Further examples include screening the presence of the HLA-B*5701 allele to prevent the hypersensitivity reactions to abacavir and the assessment of the human epidermal growth factor receptor (HER- 2) expression for trastuzumab therapy of breast cancer or that of KRAS mutation status for cetuximab or panitumumab therapy in colorectal cancer. Moreover, the application of pharmacogenetics and pharmacogenomics to therapies used in the treatment of osteoarticular diseases (e.g. rheumatoid arthritis, osteoporosis) holds great promise for tailoring therapy with clinically relevant drugs (e.g. disease-modifying antirheumatic drugs, vitamin D, and estrogens). Although the classical candidate gene approach has helped unravel genetic variants that influence clinical drug responsiveness, gene-wide association studies have recently gained attention as they enable to associate specific genetic variants or quantitative differences in gene expression with drug response. Although research findings are accumulating, most of the potential of pharmacogenetics and pharmacogenomics remains to be explored and must be validated in prospective randomized clinical trials. The genetic and molecular foundations of personalized medicine appear solid and evidence indicates its growing importance in healthcare
Mini E-book: Edukasi Perilaku Toxic Dalam Hubungan Pacaran
Full text linkProduksi mini e-book: Edukasi Perilaku Toxic Dalam Hubungan Pacaran merupakan tanggapan penulis akan pentingnya menjaga mental health. Berdasarkan data yang telah dikumpulkan oleh penulis, angka kekerasan dalam rumah tangga, berpacaran, serta kekerasan terhadap perempuan mengalami peningkatan tiap tahunnya. Pembuatan mini e-book ini agar masyarakat yang sedang menjalin hubungan toxic dalam pacaran dapat tersadarkan bahwa hubungannya sudah tidak sehat dan perlu mengambil tindakan penting untuk menyelesaikannya. Penulis menggabungkan visual berupa teks dan gambar ilustrasi agar memudahkan audiens memahami informasi yang penulis sajikan. Lalu pendistribusian mini e-book melalui media sosial akan memudahkan penulis dalam menjangkau target audiens.
Kata Kunci: Mini ebook, Toxic relationship, Edukasi toxicThe production of the mini-e-book, “Edukasi Perilaku Toxic Dalam Hubungan Pacaran," is the author's response to the importance of maintaining mental health. Based on the data the author has collected, the number of incidents of domestic violence, dating violence, and violence against women has increased every year. Making this mini-e-book for people who are in a toxic relationship in dating can be aware, that their relationship is unhealthy and they need to take important actions to resolve it, the author combines visuals in the form of text and illustration images to make it easier for the audience to understand the information the author presents. Then distributing the mini-e-book via social media will make it easier for the author to reach the target audience.
Keywords: mini-e-book, toxic relationship, toxic educatio
A potential novel drug combination for adjuvant therapy in lung cancer: reflections on an early phase of clinical development
No full textAbstract non disponibil
Methicillin-resistant staphylococci in clean surgery. Is there a role for prophylaxis?
No full textThe incidence of infection in clean surgery (i.e. surgery with no major contamination of the operative site) should be less than 2%, although the incidence of postoperative infections can be higher in patients with various risk factors (namely insertion of foreign bodies, a compromised immune status or prolonged duration of surgery). Although antibiotic prophylaxis has been shown to reduce the incidence of postoperative infections in clean surgery, there is still no consensus regarding its use in this area. However, for clean surgical procedures that involve implantation of foreign material, grafts or prosthetic devices, prophylaxis is well accepted and justifiable, since this practice is indicated when the benefits exceed the expected risks. Staphylococcus aureus and coagulase-negative staphylococci are responsible for 70 to 90% of wound infections in this type of surgery. First and second generation cephalosporins are considered the drugs of choice for surgical prophylaxis. Cefazolin and other cephalosporins have good tissue penetration but poor coverage against methicillin-resistant staphylococci. The frequency with which methicillin-resistant staphylococci have been recovered in nosocomial infections has increased steadily during recent years. This provides a rationale for the use of alternative antibiotics, such as the glycopeptides (vancomycin and teicoplanin), for prophylaxis in clean surgery in hospitals where the prevalence of methicillin-resistant staphylococci is high. The effectiveness and tolerability of teicoplanin as prophylaxis for orthopaedic surgery involving joint replacement were analysed in 4 randomised controlled trials. Two compared teicoplanin with cefamandole, while the others compared teicoplanin with either cefuroxime or cefazolin. The overall early wound infection rates (within 3 months) in these studies were 1.1% for teicoplanin and 1.7% for the comparator cephalosporin. The overall late infection rate was 0.2% for both treatment groups. Adverse events were attributed to the drug in 1% of patients in both treatment groups. Therefore, on the basis of these trials, single dose teicoplanin is as efficacious and as well tolerated as multiple dose cephalosporin regimens for prophylaxis in prosthetic joint surgery
Does surgical prophylaxis with teicoplanin constitute a therapeutic advance?
No full textAntibiotic prophylaxis has become standard care not only in operations characterized by high infection rates but also in the vast majority of clean surgical procedures, including those that use foreign materials, grafts or prosthetic devices as well as non-implant surgery. While use of antibiotics in clean implant surgery is undisputed, it is still controversial in clean non-implant surgery. As antibiotic prophylaxis should be directed against expected pathogens, the glycopeptides are considered suitable alternative antibiotics to first and second generation cephalosporins in clean surgical procedures associated with a high risk of wound infections due to Gram-positive bacteria, including methicillin-resistant, and for patients allergic to beta-lactam antibiotics. In deciding whether to use a glycopeptide for prophylaxis, the current wound infection rates with methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis at single institutions need to be considered, to limit the use of glycopeptides to wards where the incidence of methicillin resistance is high. Of the two available glycopeptides, teicoplanin may be preferable to vancomycin for peri-operative prophylaxis because of its excellent tissue penetration, as indicated by the large volume of distribution, lower toxicity, and particularly long half-life, allowing single-dose administration in several surgical procedures. Clinical trials with teicoplanin prophylaxis in several types of clean surgical procedures including orthopedic, cardiac, vascular and dental operations, have shown it to be efficacious. This review focuses on results from clinical studies with this glycopeptide as prophylaxis in clean surgery
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Pharmacological strategies for overcoming multidrug resistance
No full textMultidrug resistance (MDR) is a major obstacle to the effective treatment of cancer. One of the underlying mechanisms of MDR is cellular overproduction of P-glycoprotein (P-gp) which acts as an efflux pump for various anticancer drugs. P-gp is encoded by the MDR1 gene and its overexpression in cancer cells has become a therapeutic target for circumventing multidrug resistance. A potential strategy is to co-administer efflux pump inhibitors, although such reversal agents might actually increase the side effects of chemotherapy by blocking physiological anticancer drug efflux from normal cells. Although many efforts to overcome MDR have been made using fast and second generation reversal agents comprising drugs already in current clinical use for other indications (e.g. verapamil, cyclosporine A, quinidine) or analogues of the first-generation drugs (e.g. dexverapamil, valspodar, cinchonine), few significant advances have been made. Clinical trials with third generation modulators (e.g. biricodar, zosuquidar, and laniquidar) specifically developed for MDR reversal are ongoing. The results however are not encouraging and it may be that the perfect reverser does not exist. Other approaches to multidrug resistan cereversal have also been considered: encapsulation of anthracyclines in liposomes or other carriers which deliver these drugs selectively to tumor tissues, the use of P-gp targeted antibodies such as UIC2 or the use of antisense strategies targeting the MDR1 messenger RNA. More recently, the development of transcriptional regulators appears promising. Also anticancer drugs that belong structurally to classes of drugs extruded from cells by P-gp but that are not substrates of this drug transporter may act as potent inhibitors of MDR tumors (e.g. epothilones, second generation taxanes). Taking advantage of MDR has also been studied. Bone marrow suppression, one of the major side effects of cancer chemotherapy, can compromise the potential of curative and palliative chemotherapy. It is conceivable that drug resistance gene transfer into bone marrow stem cells may be able to reduce or abolish chemotherapy-induced myelosuppression and facilitate the use of high dose chemotherapy. Clinical trials of retroviral vectors containing drug resistance genes have established that the approach is safe and are now being designed to address the therapeutically relevant issues. © 2006 Bentham Science Publishers Ltd
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