Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.
Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.
Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available. 相似文献
Intraoperative and postoperative free flap monitoring by means of oxygen tension measurement was carried out in 11 patients. We used an invasive flexible microcatheter that allowed for measurement of oxygen tension in all types of free flaps. Two cases of the measured flaps were buried free flaps which do not allow monitoring by clinical assessment. All flaps monitored in this study survived. One case of displacement of the microcatheter occurred. In one patient, the tissue pO2 monitor successfully detected early vascular thrombosis with subsequent reoperation and salvage of the free flap. 相似文献
During 1983 and 1984, 1305 patients underwent 1,400 pulmonary artery (PA) catheterizations. Successful placement was achieved in 1397 (99.6%) of 1,403 attempts. The catheters were inserted via the right internal jugular vein on 1364 occasions. The median duration of monitoring was 28 h with a range from 3 to 220 h. Central venous puncture complications included carotid artery puncture in 67 instances (4.8%) and pneumothorax in one patient. Insertion of the catheters was associated with supraventricular arrhythmias on 11 occasions, ventricular arrhythmias on 930 (66.4%), right bundle branch block on two and a total heart block on one occasion. Eighteen (2.3%) of the 794 cultured catheter tips were positive. An in situ time of more than 72 h was associated with a significantly higher percentage (7.2%) of positive tip cultures compared with an in situ time of less than 72 h (P less than 0.01). Repeated PA catheterization was not associated with significantly more complications than the initial catheterization. The results show that monitoring with a PA catheter in cardiac surgical patients is associated with a low incidence of morbidity. 相似文献
Remote telemetry may facilitate the management of implantable devices. We tested the reliability of a new automatic, wireless home monitoring (HM) system that archives data every 24 hours. We retrospectively analyzed archival data from 276 consecutive pacing system implants to define temporal atrial fibrillation (AF) patterns and associated ventricular rate. An "AF day" was defined by a >20%/24 hour mode switch (MS) duration, irrespective of the MS number. Management decisions resulting from transmissions were noted. A pilot study confirmed that 89% of 22,356 transmissions were successful, of which >90% were received in <5 minutes. Data integrity was 100% preserved. Overall, AF developed in 29 patients (10.5%), representing a total of 645 AF days (mean = 22.2 ± 29.6 AF, median = 9 days), over 12 ± 2 months of monitoring. AF was infrequent (50% of 24 hours. Ventricular rates during 645 AF days in 29 patients averaged 95.1 ± 9.9 beats/min (median = 94 beats/min). Ventricular rates were >80 beats/min in 25 ± 30 AF days (median = 11 days). HM enabled rapid anticoagulation decisions. In recipients of implantable devices, automatic wireless telemetry with HM was efficient and reliable. Its application may overcome some current challenges in AF management by early notification and precise measurement of both AF burden and ventricular rate during AF. 相似文献
Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy. 相似文献
Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events. 相似文献
The continuous glucose monitor market is just starting to develop. Current trends in the availability of diabetes information tools highlight the need for standard data presentation for continuous glucose monitors. These trends and their implications are discussed. This article proposes a set of standards for blood glucose data presentation. If device manufacturers adopt these standards, they will ensure that their continuous glucose monitors meet both the short-term and the long-term needs of users. This should increase the demand for these monitors and enable future device developments that appeal to a wider range of users. 相似文献