NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine

6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP. One hundred and sixty-nine pediatric patients were enrolled and their genotypes were determined. Patients who carried NUDT15¹3 and NUDT15¹2 genotypes were at a 10–15 fold higher risk of severe neutropenia than those of the wild-type during the early months of the maintenance phase. Risk of neutropenia was not significantly increased in patients with other NUDT15 variants as well as in patients with TPMT, ITPA or ABCC4 variants. These results suggest that NUDT15 polymorphisms particularly, NUDT15¹3 and NUDT15¹2, play major roles in 6-MP-induced severe hematotoxicity even when using a standard low dosage of 6-MP and genotyping of these variants is necessary in order to obtain precise tolerance doses and avoid severe hematotoxicity in pediatric patients.     

Outcome of conservative treatment of primary vesicoureteral reflux in 87 Thai children in a single center

AIM: To evaluate the outcome of primary vesicoureteral reflux (VUR) using conservative treatment. METHODS: Eighty-seven children with primary VUR who had been treated with a conservative medical regimen and monitored through a yearly cystogram were recruited for the study. The study was conducted at the Pediatric Nephrology Clinic in Songklanagarind Hospital, the major tertiary care center in southern Thailand. Statistical analyses using Kaplan-Meier survival curves, chi-squared test, Fisher's exact test and multivariate analysis with Cox regression were performed. RESULTS: The study group consisted of 41 boys and 46 girls, with a total of 133 VUR. The age of the boys was significantly lower than that of the girls (P < 0.001). Resolution of the low grades (grades I-III) of VUR was significantly more frequent than that of the high grades (grades IV-V) (68/95, 72%vs 14/38, 37%; P < 0.001). Using the Kaplan-Meier survival analysis and log-rank test, the resolutions of VUR in boys versus girls, and age <1 years versus >or=1 years were not significantly different (P = 0.2252 and 0.4756, respectively). Low-grade VUR and unilateral VUR had significantly higher probabilities of resolution than high-grade VUR and bilateral VUR, respectively (P = 0.0041 and 0.0467, respectively). Multivariate Cox regression analysis indicated that among low-grade VUR, boys and unilateral VUR had significantly higher probabilities of resolution. Among the high-grade VUR, neither sex nor laterality had a significant effect on the probabilities of VUR resolution. CONCLUSION: This study offers more evidence that children with low-grade VUR have a higher chance of reflux resolution if they are boys and have only unilateral VUR. There is still no good guide for resolution of reflux in children with high-grade VUR.     

Strong linkage disequilibrium of a HbE variant with the (AT)9(T)5 repeat in the BP1 binding site upstream of the β-globin gene in the Thai population

A binding site for the repressor protein BP1, which contains a tandem (AT)_x(T)_y repeat, is located approximately 530 bp 5 to the human -globin gene (HBB). There is accumulating evidence that BP1 binds to the (AT)₉(T)₅ allele more strongly than to other alleles, thereby reducing the expression of HBB. In this study, we investigated polymorphisms in the (AT)_x(T)_y repeat in 57 individuals living in Thailand, including three homozygotes for the hemoglobin E variant (HbE; 26Glu->Lys), 22 heterozygotes, and 32 normal homozygotes. We found that (AT)₉(T)₅ and (AT)₇(T)₇ alleles were predominant in the studied population and that the HbE variant is in strong linkage disequilibrium with the (AT)₉(T)₅ allele, which can explain why the ^E chain is inefficiently synthesized compared to the normal ^A chain. Moreover, the mildness of the HbE disease compared to other hemoglobinopathies in Thai may be due, in part, to the presence of the (AT)₉(T)₅ repeat on the HbE chromosome. In addition, a novel (AC)_n polymorphism adjacent to the (AT)_x(T)_y repeat (i.e., (AC)₃(AT)₇(T)₅) was found through the variation screening in this study.MIM and accession numbers and URLs for data presented herein are as follows: Online Mendelian Inheritance of Man (OMIM), (for HBB [MIM 141900]). GenBank, (accession number [NG_000007.2] reference sequence information).     

从泰国传统医药立法探讨我国的中医药知识产权保护方法

近年来传统医药保护问题获得世界各国普遍关注.其中,泰国推出了以国家立法形式对传统医药知识做特殊保护的方法,对发展中国家具有一定借鉴作用.本文在介绍泰国传统医药知识产权保护政策基础上,对我国中医药知识产权保护方法提出了构想.     

The Picture of Health for Midlife and Older Women in America

This report overviews the major health problems of middle aged and older women and health care access issues. The relationship of labor force involvement to health status and insurance benefits is considered. Other payment sources such as Medicaid and Medicare are critiqued for their failure to finance needed prevention and other services.     

The dopaminergic system in the brain of the native Thai chicken, Gallus domesticus: localization and differential expression across the reproductive cycle

Dopamine (DA) has a pivotal role in avian prolactin (PRL) secretion, acting centrally through D₁ DA receptors to stimulate PRL secretion by operating through vasoactive intestinal peptide (VIP). DA also inhibits PRL secretion by activating D₂ DA receptors at the pituitary level. This study was designed to investigate the distribution of DA neurons in the native Thai chicken, utilizing tyrosine hydroxylase (TH) as a marker for dopaminergic neurons. The differential expression of hypothalamic TH immunoreactive (TH-ir) neurons was also compared across the reproductive cycle. The results revealed that TH-ir neurons and fibers were found throughout the brain of the laying hen and were predominantly located within the diencephalon and mesencephalon. The observed distribution pattern of TH immunoreactivity was consistent with that reported previously in several avian species. However, changes in the number of TH-ir neurons in the nucleus intramedialis (nI) were observed across the reproductive cycle and correlated directly with variations in PRL levels. The population of TH-ir neurons in the nI increased significantly during the egg incubation period, where circulating PRL levels were the greatest. This study indicates, for the first time, that an association exists between DA neurons and the regulation of the reproductive system in the native Thai chicken. There is a paucity of information about the reproductive neuroendocrine regulation of tropical non-seasonally breeding avian species and it is suggested that the differential expression of DA neurons in the nI might play a role in the control of VIP secretion and subsequent PRL release in such birds.     

Allergy Considerations in Implanted Neuromodulation Devices

ObjectivesAllergic reactions are rare and poorly understood complications of neuromodulation device implantation. There are currently no guidelines for management of allergic reactions to these devices and their components. Here we review the published cases of allergic reactions to implanted neuromodulatory devices and leverage the experiences of other specialties that deal with similar complications to formulate recommendations for prevention and management.Materials and MethodsA review and assessment of the literature.ResultsAllergic reactions to a number of implantable devices have been observed and published. In dentistry and orthopedics, metals such as nickel are the most frequent cause of allergic reactions. In interventional cardiology, where devices closely resemble neuromodulatory devices, titanium, silicone, and polyurethanes are the most common causes of allergic reactions. In neurosurgery, allergic reactions to implantable neuromodulatory devices are rare, and we summarize 13 cases published to date. Such allergic reactions generally present as local dermatitis, erythema, and pruritus, which can be difficult to distinguish from surgical site infection. In one published case, symptoms resolved with corticosteroid treatment, but all other cases required explantation. The successful reimplantation with a modified device was reported in some cases.ConclusionsPatients should be screened for a personal history of contact allergy before implantation procedures. A multidisciplinary approach to suspected cases of postoperative allergic reactions involving collaboration between neurosurgeons and other implanting physicians, dermatologists or allergists, and device manufacturers is recommended. In cases where an allergic reaction is suspected, an infectious etiology should be ruled out first. Clinical suspicion can then be supported with the use of patch testing, interpreted by an experienced dermatologist or allergist. If patch testing supports an allergic etiology, the implanting physician and the device manufacturer can work together to modify the device for safe reimplantation.     

探究不同评分系统评价急诊科危重症预后的应用对比

[目的]探究不同种类评分系统评价急诊科危重症预后的应用效果对比。[方法]将我院收治的184例急诊科危重症病人作为研究对象,采用不同的评分系统评价,分别是简单临床评分量表(SCS)、快速急诊内科评分量表(REMS)及急性生理与慢性健康状况评分Ⅱ量表(APACHEⅡ),对比三种评分系统标准与病人的死亡率情况、三种评分标准与病人的预后情况。[结果]在SCS评分中,>11分及6~11分病人死亡率明显高于0~5分病人死亡率,6~11分病人死亡率明显高于0~5分病人死亡率,差异具有统计学意义(P<0.05)。在REMS评分中,>16分及12~16分病人死亡率明显高于<11分病人死亡率,12~16分病人死亡率明显高于<11分病人死亡率,差异具有统计学意义(P<0.05)。在REMS评分中,>25分及15~24分病人死亡率明显高于<15分病人死亡率,15~24分病人死亡率明显高于<15分病人死亡率,差异具有统计学意义(P<0.05)。使用ROC曲线计算可见,SCS、REMS及APACHEⅡ评分的灵敏度分别为75.23%、76.44%、85.99%,特异度分别为71.23%、71.29%、80.62%,可见APACHEⅡ评分较SCS、REMS评分均具有更高的灵敏度以及特异性,差异具有统计学意义(P<0.05)。SCS、REMS评分相比灵敏度及特异性之间无明显差异(P>0.05)。[结论]SCS、REMS及APACHEⅡ这三种评分系统均能够在一定程度上对急诊科危重症病人的预后进行一定的判断,但结合急诊科危重症病人的实际情况分析,前二者的操作方法更加简便,通过对准确度进行判断可见,SCS评分具有更好的准确度,综合分析可见应用价值更高。