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Treatment Monitoring (treatment + monitoring)
Selected AbstractsBNP Consensus Panel 2004: A Clinical Approach for the Diagnostic, Prognostic, Screening, Treatment Monitoring, and Therapeutic Roles of Natriuretic Peptides in Cardiovascular DiseasesCONGESTIVE HEART FAILURE, Issue 2004Marc A. Silver MD Among the most exciting developments in the field of heart failure in recent times has been the rediscovery of the natriuretic peptide system and its pleuripotent effects on cardiac structure and function. This is particularly true of its natriuretic and hemodynamic effects. There has been an explosion of the knowledge base seeking to understand the wide range of homeostatic, regulatory, and counter-regulatory functions in which the natriuretic peptide system participates. Additional interest has been stimulated by advances in technology such as point-of-care and core laboratory BNP assays and the use of the recombinant B-type natriuretic peptide nesiritide as a treatment option. Despite this recent interest, the available literature lacks a comprehensive expert review of the current science and roles of natriuretic peptides for diagnostic, prognostic, screening, treatment monitoring, and therapeutic purposes. More importantly, a summary updating and guiding the clinician on most of these advances was lacking. An expert Consensus Panel with basic, methodological, and clinical expertise was convened to summarize current knowledge in these areas and the findings and consensus statements are contained herein. [source] A survey of neuroimaging research in European neurological departmentsEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2001K. Herholz In the international neurological literature, neuroimaging research plays an important role. Neuroimaging techniques are also of steadily increasing importance for clinical diagnosis and treatment monitoring. Therefore, neuroimaging research activities were surveyed by a questionnaire, which was completed by 100 neurological centres across Europe. It showed that most groups use magnetic resonance imaging (MRI), fMRI, computerized tomography (CT) and single photon emission computerized tomography (SPECT). Positron emission tomography (PET) and ultrasound are also employed by nearly half of the centres. Neuroimaging research involves co-operation amongst typically five to 10 disciplines. Cerebrovascular disease, dementia, cognitive disorders, epilepsy, movement disorders, brain tumours and multiple sclerosis are frequently being studied. Many groups rely on small budgets, have few full-time scientists and limited access to expensive resources. There is little exchange of scientists amongst laboratories. It was felt that funding and co-operation needed improvement in order to maintain a high standard in neuroimaging research. [source] Influence of factor IX on overall plasma coagulability and fibrinolytic potential as measured by global assay: monitoring in haemophilia BHAEMOPHILIA, Issue 1 2008N. A. GOLDENBERG Summary., We sought to determine the influence of factor IX (FIX) deficiency upon overall coagulative and fibrinolytic capacities in plasma using the clot formation and lysis (CloFAL) assay, and to investigate the role of this global assay as an adjunctive monitoring tool in haemophilia B. CloFAL assay parameters were measured in vitro in platelet-poor plasma in relation to FIX activity and antigen (FIX:Ag), and were determined ex vivo among FIX-deficient patients (n = 41) in comparison to healthy individuals (n = 48). Supplementation of FIX-deficient plasma with FIX in vitro demonstrated a non-linear concentration dependence of FIX upon overall plasma coagulability. Ex vivo, coagulability was significantly decreased in FIX-deficient vs. healthy subjects among adults [median coagulation index (CI): 4% vs. 104% respectively; P < 0.001] and children (median CI: 9% vs. 63%; P < 0.001). Fibrinolytic capacity was increased in adult FIX-deficient vs. healthy subjects (median fibrinolytic index: 216% vs. 125%, respectively, P < 0.001), and was supported by a trend in shortened euglobulin lysis time (ELT). Severe haemophilia B patients showed heterogeneity in aberrant CloFAL assay waveforms, influenced partly by FIX:Ag levels. Patients with relatively preserved FIX:Ag (i.e. dysfunctional FIX) exhibited a shorter time to maximal amplitude in clot formation than those with type I deficiency. During patient treatment monitoring, markedly hypocoagulable CloFAL assay waveforms normalized following 100% correction with infused FIX. The CloFAL global assay detects FIX deficiency, demonstrates differences in coagulability between dysfunctional FIX and type I deficiency, and appears useful as an adjunctive test to routine FIX measurement in monitoring haemophilia B treatment. [source] Should TPMT genotype and activity be used to monitor 6-mercaptopurine treatment in children with acute lymphoblastic leukaemia?JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2007M. Fakhoury PharmD PhD Summary Background and objective: The activity of thiopurine S -methyltransferase (TPMT), a key enzyme in the metabolism of purine analogues, displays wide inter-subject variability partly due to a genetic polymorphism. Previous studies have suggested adjusting purine analogues dosing according to TPMT activity but measurements are costly and time-consuming. It is still unclear, especially under treatment, whether the simpler TPMT genotyping reliably predicts enzyme activity. Our aim was to study the possible correlation of TPMT genotype with phenotype. Methods: We determined the genotypic status and TMPT activity, at diagnosis and after 6 months of maintenance therapy, of 118 children with acute lymphoblastic leukaemia (ALL). Results and Discussion: Eighty-nine per cent of the children had a homozygous wild-type genotype (group 1), 11% had one or two mutant allele(s) (group 2). At both time points, TPMT activity (U/mL peripheral red blood cell) was significantly higher in group 1 than in group 2 (P < 0·001) but inter-group levels overlapped considerably. There was considerable heterogeneity in the percentage increase in TPMT activity after therapy, and little correlation between metabolites ratio [6-methylmercaptopurine derivative/6-thioguanine nucleotides (6-TGN)] and TPMT activity at the end of 6 months' maintenance treatment. These results show that TPMT activity cannot be used as an accurate tool for 6-mercaptopurine monitoring. Conclusion: Genotyping at diagnosis identifies patients with a homozygous mutant TPMT and may prevent severe and life-threatening toxicity. ALL treatment monitoring should preferentially be based on repeated determinations of intracellular active metabolites (6-TGN) and methylated metabolites. [source] The pharmacology of radiolabeled cationic antimicrobial peptidesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2008Carlo P.J.M. Brouwer Abstract Cationic antimicrobial peptides are good candidates for new diagnostics and antimicrobial agents. They can rapidly kill a broad range of microbes and have additional activities that have impact on the quality and effectiveness of innate responses and inflammation. Furthermore, the challenge of bacterial resistance to conventional antibiotics and the unique mode of action of antimicrobial peptides have made such peptides promising candidates for the development of a new class of antibiotics. This review focuses on antimicrobial peptides as a topic for molecular imaging, infection detection, treatment monitoring and additionally, displaying microbicidal activities. A scintigraphic approach to studying the pharmacokinetics of antimicrobial peptides in laboratory animals has been developed. The peptides were labeled with technetium-99m and, after intravenous injection into laboratory animals, scintigraphy allowed real-time, whole body imaging and quantitative biodistribution studies of delivery of the peptides to the various body compartments. Antimicrobial peptides rapidly accumulated at sites of infection but not at sites of sterile inflammation, indicating that radiolabeled cationic antimicrobial peptides could be used for the detection of infected sites. As the number of viable micro-organisms determines the rate of accumulation of these peptides, radiolabeled antimicrobial peptides enabled to determine the efficacy of antibacterial therapy in animals to be monitored as well to quantify the delivery of antimicrobial peptides to the site of infection. The scintigraphic approach provides to be a reliable method for investigating the pharmacokinetics of small cationic antimicrobial peptides in animals and offers perspective for diagnosis of infections, monitoring antimicrobial therapy, and most important, alternative antimicrobial treatment infections with multi-drug resistant micro-organisms in humans. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci [source] Monitoring for drug side-effects in inflammatory bowel diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2002R. N. Cunliffe The side-effects suitable for monitoring in patients with inflammatory bowel disease being treated with the four main groups of drugs (5-aminosalicylic acid preparations, azathioprine and 6-mercaptopurine, methotrexate, and corticosteroids) are reviewed. On the basis of the reported frequency, severity and timing of side-effects, a practical scheme of monitoring is recommended. This includes a baseline measurement of full blood count, creatinine and liver function tests in all patients. In the absence of worrying symptoms, we recommend the following: (i) no monitoring for sulfasalazine; (ii) for other 5-aminosalicylic acid preparations, the meas- urement of creatinine at 6 and 12 months and then annually; (iii) for azathioprine/6-mercaptopurine, thiopurine methyltransferase genotype/phenotype determination has no role in treatment monitoring, but a full blood count at 2 weeks, 1 month, 3 months and then every 3 months should be performed; (iv) for methotrexate, a full blood count and liver function tests should be performed every 3 months; (v) for steroids, dual energy X-ray absorptiometry bone scanning should be performed at the start of therapy, every year in which steroids are used if the T score is < 0, and every 3,5 years if the T score is > 0. [source] Quantitative MRI for the assessment of bone structure and function,NMR IN BIOMEDICINE, Issue 7 2006Felix W. Wehrli Abstract Osteoporosis is the most common degenerative disease in the elderly. It is characterized by low bone mass and structural deterioration of bone tissue, leading to morbidity and increased fracture risk in the hip, spine and wrist,all sites of predominantly trabecular bone. Bone densitometry, currently the standard methodology for diagnosis and treatment monitoring, has significant limitations in that it cannot provide information on the structural manifestations of the disease. Recent advances in imaging, in particular MRI, can now provide detailed insight into the architectural consequences of disease progression and regression in response to treatment. The focus of this review is on the emerging methodology of quantitative MRI for the assessment of structure and function of trabecular bone. During the past 10 years, various approaches have been explored for obtaining image-based quantitative information on trabecular architecture. Indirect methods that do not require resolution on the scale of individual trabeculae and therefore can be practiced at any skeletal location, make use of the induced magnetic fields in the intertrabecular space. These fields, which have their origin in the greater diamagnetism of bone relative to surrounding marrow, can be measured in various ways, most typically in the form of R2,, the recoverable component of the total transverse relaxation rate. Alternatively, the trabecular network can be quantified by high-resolution MRI (µ-MRI), which requires resolution adequate to at least partially resolve individual trabeculae. Micro-MRI-based structure analysis is therefore technically demanding in terms of image acquisition and algorithms needed to extract the structural information under conditions of limited signal-to-noise ratio and resolution. Other requirements that must be met include motion correction and image registration, both critical for achieving the reproducibility needed in repeat studies. Key clinical applications targeted involve fracture risk prediction and evaluation of the effect of therapeutic intervention. Copyright © 2006 John Wiley & Sons, Ltd. [source] Assessment is not enough: a randomized controlled trial of the effects of HRQL assessment on quality of life and satisfaction in oncology clinical practicePSYCHO-ONCOLOGY, Issue 12 2007Sarah K. Rosenbloom Abstract The potential benefits of health-related quality of life (HRQL) assessment in oncology clinical practice include better detection of problems, enhanced disease and treatment monitoring and improved care. However, few empirical studies have investigated the effects of incorporating such assessments into routine clinical care. Recent randomized studies have reported improved detection of and communication about patients' concerns, but few have found effects on patient HRQL or satisfaction. This study examined whether offering interpretive assistance of HRQL results would improve these patient outcomes. Two hundred and thirteen participants with metastatic breast, lung or colorectal cancer were randomly assigned to one of three conditions: usual care; HRQL assessment or HRQL assessment followed by a structured interview and discussion. Interviews about patients' assessment responses were conducted by a research nurse, who then presented HRQL information to the treating nurse. HRQL and treatment satisfaction outcomes were assessed at 3 and 6 months. No significant differences were found between study conditions in HRQL or satisfaction. Results suggest that routine HRQL assessment, even with description of results, is insufficient to improve patient HRQL and satisfaction. It is suggested that positive effects may require supplementing assessment results with specific suggestions for clinical management changes. Copyright © 2007 John Wiley & Sons, Ltd. [source] Direct determination of phosphorylated intracellular anabolites of stavudine (d4T) by liquid chromatography/tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 16 2001Alain Pruvost The objective was to develop and validate a routine assay for active intracellular anabolites of stavudine (d4T), a nucleoside reverse transcriptase inhibitor in human PBMC, applicable to pharmacokinetic studies and treatment monitoring. This was achieved using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS), which theoretically allies optimum sensitivity, specificity and high sample throughput. After cellular lysis in a Tris/methanol buffer, the extract spiked with 2[H8]-ATP (internal standard) is directly injected into the LC/MS/MS system. Phosphorylated metabolites of d4T as well as deoxythymidine-triphosphate, the competitor on the reverse transcriptase, are separated from d4T on a reverse-phase microbore column with ion pairing. The detection is performed in the multiple reaction monitoring (MRM) mode after drug ionisation in negative mode electrospray. The limit of quantitation for d4T-TP was 138 fmol per 7,mL blood (9.8 fmol per 106 cells) and CV% for repeatability and intermediate precision were lower than 15%. Stability of compounds was checked before and during the process of isolation of PBMC. Cellular samples from several d4T-treated patients were successfully analysed using this method and d4T-triphosphate and deoxythymidine triphosphate were recovered. In conclusion, we have developed and validated a routine LC/MS/MS method that allows the simultaneous determination of mono-, di- and triphosphorylated anabolites of d4T in PBMC as well as the natural corresponding triphosphate in one analysis. For the first time, the chain terminator ratio (d4T-TP/dT-TP) could be directly measured. This method can be used simply and routinely on more than 35 samples per day. Extension to other nucleoside analogues is under development. Copyright © 2001 John Wiley & Sons, Ltd. [source] Diagnosis of thrombotic thrombocytopenic purpura based on modulation by patient plasma of normal platelet adhesion under flow conditionBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2003Boris Shenkman Summary. We have designed a simple test for the early diagnosis and treatment monitoring of thrombotic thrombocytopenic purpura (TTP). We examined plasma from 24 TTP patients and normal plasma using a cone and plate(let) analyser (CPA). Test plasma was mixed with citrated normal whole blood (group O) and subjected to flow at a shear rate of 1800/s. Mixing normal plasma (12·5, 25, 50 or 75 µl) with heterologous normal whole blood (final volume of 200 µl) resulted in a decrease of surface coverage (SC, maximally by 63%) and, to a lesser extent, of average size (AS, maximally by 37%) due to dilution of the blood sample. In contrast, mixing the same quantities of acute TTP plasma with normal blood yielded an increase in both SC (up to 125%) and AS (up to 130%). Increased SC and/or AS were detected in all 15 patients in acute phase and in three out of 14 patients in remission. Following repeated plasmapheresis, the enhanced platelet deposition in five patients with acute TTP returned to almost normal patterns. Mixing plasma from patients with other thrombocytopenic conditions in this way resulted in a decrease in both SC and AS, and did not differ from control subjects. In conclusion, the CPA is a simple and specific laboratory test that can be used for the diagnosis and monitoring of plasma exchange therapy in TTP. 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