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.     

Low prevalence of heparin-induced thrombocytopenia after cardiac surgery in Thai patients

Introduction

Heparin induced-thrombocytopenia (HIT) has been well recognized in Western countries. However, there are no data in the Thai population. We therefore investigated the prevalence of anti-platelet factor 4 (PF4)/heparin antibodies, HIT, and its thrombotic complications in Thai patients undergoing cardiac surgery using unfractionated heparin.

Materials and methods

Seventy-three consecutive patients were prospectively enrolled in this study. Blood samples before operation and week 1, week 2, and week 3 after operation were collected from each patient for HIT antibody screening by enzyme-linked immunosorbent assay using IgG antibody specific to the PF4/heparin complex. Positive samples were further analyzed by ¹⁴C-serotonin release assay. Complete blood count was performed daily during the first week, then weekly for 3 weeks.

Results

No patient had detectable anti-PF4/heparin antibodies at baseline. Five patients sero-converted during the course of the study for anti-PF4/heparin IgG: 3 (4.1%) at week 1, 4 (5.5%) at week 2, and 5 (6.8%) at week 3 after surgery. However, none of these patients had anti-PF4/heparin antibodies that resulted in ¹⁴C-serotonin release to be considered clinically significant antibodies. Post-operative thrombocytopenia after the operation was found in 35 patients (47.9%), but was not considered to be caused by HIT. Thromboembolic events occurred in 3 patients (4.1%) during follow up; however, none of these patients had positive PF4/heparin antibody tests.

Conclusions

Our study represents the first study to examine Thai patients exposed to heparin in the context of cardiac surgery. We found a lower prevalence of positive anti-PF4/heparin antibodies and clinical HIT than previously published studies.     

Post rtPA CT brain may not be mandatory in all stroke patients when resources are limited

Background: Routine neuroimaging of the brain is performed after recombinant-tissue-plasminogen activator (rtPA) treatment in patients with acute ischemic stroke. However, in situation where resources are limited, it is not known if a follow-up computed tomography (CT) is beneficial for guiding the treatment plan or not. The purpose of this study is to investigate the need for a follow-up CT in patients with acute stroke after rtPA treatment. Methods: Patients who were treated with intravenous rtPA were included. Clinical symptoms/signs of the patients were evaluated at 24 h after rtPA treatment compared with baseline NIHSS. The need for a follow-up CT after rtPA treatment was assessed by comparison of the early clinical changes with the CT brain results that would affect the management plan: presence of hemorrhagic transformation, malignant MCA infarction, or large cerebellar infarction. Results: 200 patients were included. 19 patients (9.5%) had complete recovery. CT post rtPA revealed no change in these patients. In 105 patients who had early improvement with NIHSS of 1–10 at 24 h, follow-up CT findings did not change the plan of management in 85%. Follow-up CTs may help in planning further management in 65% and 67% of the patients who had NIHSS > 10 at 24 h and early worsening, respectively. Conclusions: CT post rtPA may not be required in patients with early clinical recovery (NIHSS = 0). However, in patients with residual severe deficit post rtPA or patients with early worsening or suspected posterior circulation stroke, CT post rtPA is still needed.     

Determination of melatonin content in traditional Thai herbal remedies used as sleeping aids

Background

Melatonin content was screened in leaves of seven edible herbs used as sleeping aids in Thai traditional medicine. These plants are Piper nigrum L, Sesbania glandiflora (L.) Desv., Sesbania sesban (L.) Merr., Senna tora (L.) Roxb., Moringa oleifera Lam., Momordica charantia L. and Baccaurea ramiflora Lour. Dried leaves were extracted by sonication in methanol for six hours at room temperature, and then melatonin was purified by C18 solid phase extraction (SPE). Melatonin was then quantified by a validated RP-C18 HPLC method with fluorescent detection.

Findings

Melatonin contents in extracts of B. ramiflora, S. glandiflora, M. charantia, S. tora and S. sesban were 43.2, 26.3, 21.4, 10.5 and 8.7 ng/g of dry sample weight, respectively. The highest melatonin content was from P. nigrum extract (1092.7 ng/g of dry sample weight). Melatonin was not detected in the extract of M. oleifera. Melatonin identification was confirmed by ELISA.

Conclusions

Melatonin was found in six of the seven herbs in the traditional Thai sleeping recipe. One of these, P. nigrum, exhibited an encouragingly high amount of melatonin.