The cauliflower mosaic virus translational transactivator interacts with the 60S ribosomal subunit protein L18 of Arabidopsis thaliana

The cauliflower mosaic virus (CaMV) open reading frame VI product (P6) is involved in several aspects of the infectious cycle. P6 specifically controls the synthesis of other CaMV proteins by transactivating their expression from the polycistronic 35S RNA. By far-Western assays, we have demonstrated that P6 interacts with proteins from both healthy and CaMV-infected leaves of Arabidopsis thaliana. These proteins are found in ribosome-enriched extracts, suggesting that they participate in the translation process. One of these proteins, identified by microsequencing, corresponds to the 60S ribosomal subunit protein L18 (RPL18). Its cDNA was cloned and expressed in Escherichia coli, and the resulting RPL18 protein was shown to interact with the minimal region required for translational transactivation, designated the miniTAV domain of P6.     

Using Economic Evaluation in Policy Decision-Making in Asian Countries: Mission Impossible or Mission Probable?

Objectives and Methods:  This article provides an extensive review of literature and an in-depth analysis aimed at introducing potential applications of economic evaluation and at addressing the barriers that could prohibit the use or diminish the usefulness of economic evaluation in Asian settings. It also proposes the probable solutions to overcome these barriers.
Results:  Potential uses of economic evaluation include the development of public reimbursement lists, price negotiation, the development of clinical practice guidelines, and communicating with prescribers. Two types of barriers to using economic evaluation, namely barriers relating to the production of economic evaluation data and decision context-related barriers, are identified. For the first sort of barrier, the development of the national guidelines, the development of economic evaluation database, planning and use of economic evaluation in a systematic manner, and prioritization of topics for assessment are recommended. Furthermore, educating potential users and the public, making the economic evaluation process transparent and participatory, and incorporating other health preferences into the decision-making framework have been promoted to conquer decision context-related barriers.
Conclusions:  It seems practically impossible to adopt other countries' approaches using economic evaluation for priority setting because of several constraints specifically related to the context of each setting. Nevertheless, given a better understanding of its resistance, and proper policies and strategies to overcome the barriers applied, it is more than probable that a method with system/mechanisms specifically designed to fit particular settings will be used.     

Economic Impact on Health-Care Costs Related to Major Diseases Including HIV/AIDS due to Alcohol Drinking among Thai Populations

Objective:  The objective of this study was to estimate health-care costs because of diseases caused by alcohol consumption based on health system's perspective.
Methods:  Total direct health-care costs of alcohol drinking were the summation of the costs of alcohol drinking in inpatient and outpatient departments due to chronic diseases and acute conditions using prevalence-based approach. The alcohol-attributable fractions, defined as the proportion of a disease or acute condition in a population attributable to alcohol drinking, were calculated to obtain the number of patients in each disease or acute condition attributable to alcohol drinking. Health-care costs of alcohol drinking were estimated by multiplying the number of patients in each disease category attributable to alcohol drinking with the unit cost of treatment.
Results:  Total health-care costs attributed to alcohol in this research were 5491 million baht (i.e., outpatient department [2488 million baht] and inpatient department [3003 million baht]). Cost derived from inpatient department accounted for 55% of the total health-care cost attributed to alcohol.
Conclusions:  The result of this study suggested that alcohol drinking was significantly associated with a large number of health-care costs in Thailand. Estimation of health-care costs related to alcohol drinking would provide an important insight into future policy appraisal and evaluation.     

Cost-Utility Analysis of Dasatinib and Nilotinib in Patients With Chronic Myeloid Leukemia Refractory to First-Line Treatment With Imatinib in Thailand

Background

Recently, the second-generation tyrosine kinase inhibitors dasatinib and nilotinib have emerged as alternative treatments in patients with chronic myeloid leukemia (CML) who are resistant to or intolerant of imatinib.

Objective

This article aimed to assess the cost utility and budget impact of using dasatinib or nilotinib, rather than high-dose (800-mg/d) imatinib, in patients with chronic phase (CP) CML who are resistant to standard-dose (400-mg/d) imatinib in Thailand.

Methods

A Markov simulation model was developed and used to estimate the lifetime costs and outcomes of treating patients aged ≥38 years with CP-CML. The efficacy parameters were synthesized from a systematic review. Utilities using the European Quality of Life–5 Dimensions tool and costs were obtained from the Thai CML population. Costs and outcomes were compared and presented as the incremental cost-effectiveness ratio in 2011 Thai baht (THB) per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were performed to estimate parameter uncertainty.

Results

From a societal perspective, treatment with dasatinib was found to yield more QALYs (2.13) at a lower cost (THB 1,631,331) per person than high-dose imatinib. Nilotinib treatment was also found to be more cost-effective than high-dose imatinib, producing an incremental cost-effectiveness ratio of THB 83,328 per QALY gained. This treatment option also resulted in the highest number of QALYs gained of all of the treatment options. The costs of providing dasatinib, nilotinib, and high-dose imatinib were estimated at THB 5 billion, THB 6 billion, and THB 7 billion, respectively.

Conclusions

Treatment with dasatinib or nilotinib is likely to be more cost-effective than treatment with high-dose imatinib in CP-CML patients who do not respond positively to standard-dose imatinib in the Thai context. Dasatinib was found to be more cost-effective than nilotinib.     

Therapeutic implications of tumor interstitial fluid pressure in subcutaneous RG-2 tumors

Increased interstitial fluid pressure (IFP) in brain tumors results in rapid removal of drugs from tumor extracellular space. We studied the effects of dexamethasone and hypothermia on IFP in s.c. RG-2 rat gliomas, because they could potentially be useful as means of maintaining drug concentrations in human brain tumors. We used dexamethasone, external hypothermia, combined dexamethasone and hypothermia, and infusions of room temperature saline versus chilled saline. We measured tumor IFP and efflux half-time of 14C-sucrose from tumors. In untreated s.c. tumors, IFP was 9.1 +/- 2.1 mmHg, tumor temperature was 33.7 degrees C +/- 0.7 degrees C, and efflux half-time was 7.3 +/- 0.7 min. Externally induced hypothermia decreased tumor temperature to 8.9 degrees C +/- 2.9 degrees C, tumor IFP decreased to 3.2 +/- 1.1 mmHg, and efflux half-time increased to 13.5 min. Dexamethasone decreased IFP to 2.4 +/- 1.0 mmHg and increased efflux half-time to 15.4 min. Combined hypothermia and dexamethasone further increased the efflux half-time to 17.6 min. We tried to lower the tumor temperature by chilling the infusion solution, but at an infusion rate of 48 mul/min, the efflux rate was the same for room temperature saline and 15 degrees C saline. The efflux rate was increased in both infusion groups, which suggests that efflux due to tumor IFP and that of the infusate were additive. Since lowering tumor IFP decreases efflux from brain tumors, it provides a means to increase drug residence time, which in turn increases the time-concentration exposure product of therapeutic drug available to tumor.     

A systematic review of economic evaluation literature in Thailand: are the data good enough to be used by policy-makers?

In many countries, including Thailand, there is an increasing impetus to use economic evaluation to allow more explicit and transparent healthcare priority setting. However, an important question for policy makers in low- and middle-income countries is whether it is appropriate and feasible to introduce economic evaluation data into healthcare priority-setting decisions. In addition to ethical, social and political issues, information supply challenges need to be addressed. This paper systematically reviewed the literature on economic evaluation of health technology in Thailand published between 1982 and 2005. Its aim was to analyse the quantity, quality and targeting of economic evaluation studies that can provide a framework for those conducting similar reviews in other settings. The review revealed that, although the number of publications reporting economic evaluations has increased significantly in recent years, serious attention needs to be given to the quality of reporting and analysis. Furthermore, there is an absence of economic evaluation publications for 15 of the top 20 major health problems in Thailand, indicating a poor distribution of research resources towards the determination of cost-effective interventions for diminishing the disease burden of certain major health problems. If economic evaluation is only useful for policy makers when performed correctly and reported accurately, these findings depict information barriers to using economic evaluation to assist health decision-making processes in Thailand.     

Central nervous system involvement in Rosai-Dorfman disease: Report of a case with a review of the literature

A 55-year-old woman had Rosai-Dorfman disease (RDD) forming multiple masses of abnormal histiocytes, three in the cranial cavity and one in the left orbit that was proptotic. The masses were removed and found to consist of abnormal histiocytes that were immunoreactive to cluster designation 68 (CD68) (KP-1), alpha-1-antitrypsin and S-100 protein and showed emperipolesis. A review of 28 cases of RDD, including this instance, revealed a ratio of 5:2 between males and females and a mean age of 32 years. Intracranial involvement was much more frequent than that of the spinal cord. Histologically, central nervous system (CNS) RDD must be distinguished from meningioma, Langerhans cell histiocytosis, and plasma cell granuloma. Surgical extirpation appears to be the treatment of choice for this idiopathic histiocytic proliferative disorder of the CNS in comparison with radiotherapy and steroid treatment, which have also been tried.     

Astroblastoma: Report of a case with microsatellite analysis

A 5‐year‐old girl who developed progressive headache, vomiting, and left hemiparesis was found to have a cystic tumor with an enhanced mural nodule in the right frontoparietal region on a computed tomography examination. The lesion was histologically and ultrastructurally verified as an astroblastoma, an uncommon neuroepithelial tumor of uncertain origin. Molecular analysis using 17 microsatellite markers on chromosomes 9, 10, 11, 17, 19, and 22 showed loss of heterozygosity at the D19S412 locus on the long arm of chromsome 19. This observation suggests that there is a tumor suppressor gene in this chromosomal region, which plays a role in the pathogenesis of astroblastoma.