A barrier to eliminating Plasmodium vivax malaria is inadequate treatment of infected patients. 8-Aminoquinoline–based drugs clear the parasite; however, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk for hemolysis from these drugs. Understanding the performance of G6PD deficiency tests is critical for patient safety. Two quantitative assays and two qualitative tests were evaluated. The comparison of quantitative assays gave a Pearson correlation coefficient of 0.7585 with significant difference in mean G6PD activity, highlighting the need to adhere to a single reference assay. Both qualitative tests had high sensitivity and negative predictive value at a cutoff G6PD value of 40% of normal activity if interpreted conservatively and performed under laboratory conditions. The performance of both tests dropped at a cutoff level of 45%. Cytochemical staining of specimens confirmed that heterozygous females with > 50% G6PD-deficient cells can seem normal by phenotypic tests.
No clear correlation between the mutations studied and DPD activity could be established in this study. However, larger-scale prospective studies are needed to better assess the reported genotype-phenotype correlations.
Purpose. The purpose of the current study were to assess the safety and feasibility of repetitive intratumoral administration of E10A, an adenoviral vector encoding the wild-type endostatin gene, to patients with solid tumors, and to evaluate its biologic effect and the pharmacokinetics of endostatin.Methods. Patients were treated with escalating doses from 1 × 10 10 VP to 1 × 10 12 VP of E10A intratumorally on days 1 and 8. Patients were assessed for toxicity and viral shedding, and antitumor response was evaluated by imaging techniques and tumor biopsy. Circulating levels of endostatin were examined.Results. Fifteen patients received 29 injections of E10A. No dose-limiting toxicity was developed, and the maximum tolerated dose had not yet been reached. Fever and local reaction of injection site were common, but rarely severe. Mild and transient hepatotoxicity was observed in one patient. Minor response of injected tumor was achieved and improvement of the control tumor was observed in one patient with nasopharyngeal carcinoma, and tumor necrosis was occurred in two patients. Sustained elevation of serum endostatin levels was detected.Conclusion. Weekly intratumoral injection of up to 1 × 10 12 VP of E10A to patients with solid tumor is a feasible and well-tolerated procedure that exerts mild antitumor effects. A small and sustained elevation of endogenous endostatin in blood possibly has antitumor activity.
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