Publications by authors named "Thanh Liem Nguyen"

24 Publications

  • Page 1 of 1

Standardized xeno- and serum-free culture platform enables large-scale expansion of high-quality mesenchymal stem/stromal cells from perinatal and adult tissue sources.

Cytotherapy 2021 Jan 21;23(1):88-99. Epub 2020 Oct 21.

Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam.

Background Aims: Mesenchymal stem/stromal cells (MSCs) are of interest for the treatment of graft-versus-host disease, autoimmune diseases, osteoarthritis and neurological and cardiovascular diseases. Increasing numbers of clinical trials emphasize the need for standardized manufacturing of these cells. However, many challenges related to diverse isolation and expansion protocols and differences in cell tissue sources exist. As a result, the cell products used in numerous trials vary greatly in characteristics and potency.

Methods: The authors have established a standardized culture platform using xeno- and serum-free commercial media for expansion of MSCs derived from umbilical cord (UC), bone marrow and adipose-derived (AD) and examined their functional characteristics.

Results: MSCs from the tested sources stably expanded in vitro and retained their biomarker expression and normal karyotype at early and later passages and after cryopreservation. MSCs were capable of colony formation and successfully differentiated into osteogenic, adipogenic and chondrogenic lineages. Pilot expansion of UC-MSCs and AD-MSCs to clinical scale revealed that the cells met the required quality standard for therapeutic applications.

Conclusions: The authors' data suggest that xeno- and serum-free culture conditions are suitable for large-scale expansion and enable comparative study of MSCs of different origins. This is of importance for therapeutic purposes, especially because of the numerous variations in pre-clinical and clinical protocols for MSC-based products.
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http://dx.doi.org/10.1016/j.jcyt.2020.09.004DOI Listing
January 2021

Differential Wound Healing Capacity of Mesenchymal Stem Cell-Derived Exosomes Originated From Bone Marrow, Adipose Tissue and Umbilical Cord Under Serum- and Xeno-Free Condition.

Front Mol Biosci 2020 24;7:119. Epub 2020 Jun 24.

Vinmec Research Institute of Stem Cell and Gene Technology (VRISG), Vinmec Health Care System, Hanoi, Vietnam.

Exosomes are nano-scale and closed membrane vesicles which are promising for therapeutic applications due to exosome-enclosed therapeutic molecules such as DNA, small RNAs, proteins and lipids. Recently, it has been demonstrated that mesenchymal stem cell (MSC)-derived exosomes have capacity to regulate many biological events associated with wound healing process, such as cell proliferation, cell migration and blood vessel formation. This study investigated the regenerative potentials for cutaneous tissue, in regard to growth factors associated with wound healing and skin cell proliferation and migration, by exosomes released from primary MSCs originated from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) under serum- and xeno-free condition. We found crucial wound healing-mediated growth factors, such as vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), hepatocyte growth factor (HGF), and platelet-derived growth factor BB (PDGF-BB) in exosomes derived from all three MSC sources. However, expression levels of these growth factors in exosomes were influenced by MSC origins, especially transforming growth factor beta (TGF-β) was only detected in UCMSC-derived exosomes. All exosomes released by three MSCs sources induced keratinocyte and fibroblast proliferation and migration; and, the induction of cell migration is a dependent manner with the higher dose of exosomes was used (20 μg), the faster migration rate was observed. Additionally, the influences of exosomes on cell proliferation and migration was associated with exosome origins and also target cells of exosomes that the greatest induction of primary dermal fibroblasts belongs to BMMSC-derived exosomes and keratinocytes belongs to UCMSC-derived exosomes. Data from this study indicated that BMMSCs and UCMSCs under clinical condition secreted exosomes are promising to develop into therapeutic products for wound healing treatment.
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http://dx.doi.org/10.3389/fmolb.2020.00119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327117PMC
June 2020

Characterization of Angle Accuracy and Precision of 3-Degree-of-Freedom Absolute Encoder Based on NanoGPS OxyO Technology.

Sensors (Basel) 2020 Jun 19;20(12). Epub 2020 Jun 19.

HORIBA France, 14 Boulevard Thomas Gobert, 91120 Palaiseau, France.

An absolute encoder based on vision system nanoGPS OxyO was developed by HORIBA France. This encoder provides three types of position information, namely, two inplane co-ordinates and inplane angular orientation. This paper focuses on the characterization of its angular performance. To this aim, the nanoGPS OxyO system was compared with the national angle standard of the National Metrology Institute of Italy (INRIM) that had evaluated accuracy of about 0.1 µrad. The effect of image size and illumination conditions on angular measurements was studied. Precision better than 10 µrad and accuracy better than 63 µrad over 2π rotation were demonstrated. Moreover, the application of nanoGPS OxyO to the characterization of rotation bearing is presented. Small deviations from pure rotational behavior were evidenced that would have not been possible using laser interferometers. As a consequence of its accuracy and versatility, the nanoGPS OxyO encoder is expected to be useful for laboratory experiments and quality-control tasks.
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http://dx.doi.org/10.3390/s20123462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349673PMC
June 2020

Improvement in gross motor function and muscle tone in children with cerebral palsy related to neonatal icterus: an open-label, uncontrolled clinical trial.

BMC Pediatr 2019 08 22;19(1):290. Epub 2019 Aug 22.

Vinmec Research Institute of Stem Cell and Gene Technology, Hanoi, Vietnam.

Background: Although stem cell transplantation has been successfully performed for cerebral palsy (CP) related to oxygen deprivation, clinical trials involving the use of stem cell transplantation for CP related to neonatal icterus have not been reported. The aim of this study was to evaluate the effectiveness of transplantation of autologous bone marrow mononuclear cell (BMMC) for improving gross motor function and muscle tone in children with CP related to neonatal icterus.

Methods: This open-label, uncontrolled clinical trial, which included 25 patients with CP related to neonatal icterus who had a Gross Motor Function Classification System (GMFCS) score between level II and level V, was conducted between July 2014 and July 2017 at Vinmec International Hospital (Vietnam). BMMC were harvested from the patients' iliac crests. Two procedures involving BMMC transplantation via the intrathecal route were performed: the first transplantation was performed at baseline, and the second transplantation was performed 6 months after the first transplantation. Gross motor function and muscle tone were measured at three time points (baseline, 6 months, and 12 months) using the Gross Motor Function Measure (GMFM) and the Modified Ashworth Scale.

Results: In this trial, we observed significant improvement in gross motor function and a significant decrease in muscle tone values. Total score on the 88-item GMFM (GMFM-88), scores on each GMFM-88 domain, and the 66-item GMFM (GMFM-66) percentile were significantly enhanced at 6 months and 12 months after the first transplantation compared with the corresponding baseline measurements (p-values < 0.05). In addition, a significant reduction was observed in muscle tone score after the transplantations (p-value < 0.05).

Conclusion: Autologous BMMC transplantation can improve gross motor function and muscle tone in children with CP related to neonatal icterus.

Trial Registration: ClinicalTrials.gov identifier: NCT03123562 . Retrospectively registered on December 26, 2017.
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http://dx.doi.org/10.1186/s12887-019-1669-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704727PMC
August 2019

Efficient and Precise CRISPR/Cas9-Mediated MECP2 Modifications in Human-Induced Pluripotent Stem Cells.

Front Genet 2019 2;10:625. Epub 2019 Jul 2.

Immune Regulation and Cancer, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.

Patients with Rett syndrome (RTT) have severe mental and physical disabilities. The majority of RTT patients carry a heterozygous mutation in methyl-CpG binding protein 2 (MECP2), an X-linked gene encoding an epigenetic factor crucial for normal nerve cell function. No curative therapy for RTT syndrome exists, and cellular mechanisms are incompletely understood. Here, we developed a CRISPR/Cas9-mediated system that targets and corrects the disease relevant regions of the MECP2 exon 4 coding sequence. We achieved homologous recombination (HR) efficiencies of 20% to 30% in human cell lines and iPSCs. Furthermore, we successfully introduced a MECP2 mutation into the MECP2 gene in human induced pluripotent stem cells (iPSCs). Consequently, using CRISPR/Cas9, we were able to repair such mutations with high efficiency in human mutant iPSCs. In summary, we provide a new strategy for MECP2 gene targeting that can be potentially translated into gene therapy or for iPSCs-based disease modeling of RTT syndrome.
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http://dx.doi.org/10.3389/fgene.2019.00625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614930PMC
July 2019

The effects of bone marrow mononuclear cell transplantation on the quality of life of children with cerebral palsy.

Health Qual Life Outcomes 2018 Aug 14;16(1):164. Epub 2018 Aug 14.

Vinmec Research Institute of Stem Cell and Gene Technology, 458 Minh Khai Street, Hanoi, Vietnam.

Background: Quality of life (QOL) is an important factor in evaluating the effectiveness of treatment in children with cerebral palsy (CP). The aim of this study was to evaluate the effects of autologous bone marrow mononuclear cells (BM MNCs) on the QOL of children with CP.

Methods: From December 2015 to December 2016, 30 children with CP aged from 2 to 15 years received two intrathecal infusions of BM MNCs, one at baseline and the other 3 months later, at Vinmec International Hospital. The motor function and muscle tone of the patients were evaluated using the Gross Motor Function Measure (GMFM)-88 and Modified Ashworth Score, respectively. Their QOL was assessed at baseline and 6 months after the first BM MNC transplant using the Vietnamese version of the Cerebral Palsy Quality of Life Questionnaire for children (CP QOL-Child)-the parental proxy report, which comprises seven domains. Nineteen mothers (mean age: 32.9±4.9 years) and 11 fathers (mean age: 36.1±6.8 years) were invited to complete the CP QOL-Child assessment before and after the transplantations, Paired t-tests and multivariate regression analyses were used to evaluate the changes in QOL and GMFM scores and to identify the key factors correlated with the QOL score.

Results: Significant changes were observed in the children's gross motor function and muscle spasticity, as evidenced by the GMFM-88 total score, scores for each of its domains, the GMFM-66 percentile and the muscle tone (P < 0.001). Six months after the transplantations, the QOL scores of children with CP were markedly increased (P < 0.001) for all the domains, except for the domain of access to services. In the multivariate regression analysis, significant associations were found between higher age of children and higher QOL except for feeling about functioning and pain and impact of disability domains. Gross Motor Function Classification System (GMFCS) level was negatively correlated with the score of pain and impact of disability domain, while the GMFM-88 scores were positively correlated with the QOL in terms of feelings about functioning and family health domain (P < 0.05).

Conclusion: The QOL of the children with CP was noticeably improved 6 months after BM MNC transplantation and was accompanied by improvements in gross motor function and muscle tone.

Trial Registration: ClinicalTrials.gov Identifier: NCT02574923 . Registered on October 14, 2015.
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http://dx.doi.org/10.1186/s12955-018-0992-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092872PMC
August 2018

Spectrum of MECP2 mutations in Vietnamese patients with RETT syndrome.

BMC Med Genet 2018 08 6;19(1):137. Epub 2018 Aug 6.

Department of Gene Technology - Vinmec Research Institute of Stem cell and Gene Technology, 458 Minh Khai Street, Hanoi, Hai Ba Trung district, Vietnam.

Background: Rett syndrome (RTT) is a severe neurodevelopmental disorder in children characterized by a normal neurodevelopmental process in the first 6-18 months followed by a period of motor and vocal deterioration with stereotypic hand movements. Incidence of RTT is mostly due to de novo mutation in the MECP2 gene (methyl-CpG-binding protein 2).

Methods: The study assessed 27 female patients presented with classical RTT phenotype age range from 18 months to 48 months. Specialist carried out the clinical evaluation and diagnosis according to RTT diagnosis criteria. Blood samples from patients were then collected for genomic DNA extraction. We next performed MECP2 gene amplification and sequencing of the whole coding region to screen for mutations.

Result: MECP2 mutation was found in 20 patients (74%) including: 2 missense, 4 nonsense, 6 frameshift and 2 deletion mutation. The study identified 14 pathogenic mutations which we found 4 mutation, to our knowledge and extensive search, not priory reported in any mutation database or publication: c.1384-1385DelGT, c.1205insT, c.717delC and c.1132_1207del77. High percentage of C > T (70%) in CpG sites mutation was found.

Conclusion: Our result reveals a high percentage of C > T mutation in CpG hot spot, which is more prone to modification and more likely to be detected in RTT as a disorder is strictly due to de novo mutations. The study is the first to identify the mutation spectrum of MECP2 gene in Vietnamese patients and also an important step toward better diagnosis and care for RTT patients in Vietnam.
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http://dx.doi.org/10.1186/s12881-018-0658-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090653PMC
August 2018

Single YVO4:Eu nanoparticle emission spectra using direct Eu3+ ion excitation with a sum-frequency 465-nm solid-state laser.

Opt Express 2014 Aug;22(17):20542-50

We report emission spectrum measurements on single YxEu(1-x)VO4 nanoparticles. The inhomogeneous widths of the emission peaks are identical for single nanoparticles and for ensembles of nanoparticles, while being broader than those of the bulk material. This indicates that individual nanoparticles are identical in terms of the distribution of different local Eu3+ sites due to crystalline defects and confirms their usability as identical, single-particle oxidant biosensors. Moreover, we report a 465 nm solid-state laser based on sum-frequency mixing that provides a compact, efficient solution for direct Eu3+ excitation of these nanoparticles. Both these two aspects should broaden the scope of Eu-doped nanoparticle applications.
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http://dx.doi.org/10.1364/OE.22.020542DOI Listing
August 2014

Targeted next-generation sequencing on Hirschsprung disease: a pilot study exploits DNA pooling.

Ann Hum Genet 2014 Sep 20;78(5):381-7. Epub 2014 Jun 20.

Department of Surgery, The University of Hong Kong, Hong Kong, SAR, China; Department of Psychiatry, The University of Hong Kong, Hong Kong, SAR, China.

To adopt an efficient approach of identifying rare variants possibly related to Hirschsprung disease (HSCR), a pilot study was set up to evaluate the performance of a newly designed protocol for next generation targeted resquencing. In total, 20 Chinese HSCR patients and 20 Chinese sex-matched individuals with no HSCR were included, for which coding sequences (CDS) of 62 genes known to be in signaling pathways relevant to enteric nervous system development were selected for capture and sequencing. Blood DNAs from eight pools of five cases or controls were enriched by PCR-based RainDance technology (RDT) and then sequenced on a 454 FLX platform. As technical validation, five patients from case Pool-3 were also independently enriched by RDT, indexed with barcode and sequenced with sufficient coverage. Assessment for CDS single nucleotide variants showed DNA pooling performed well (specificity/sensitivity at 98.4%/83.7%) at the common variant level; but relatively worse (specificity/sensitivity at 65.5%/61.3%) at the rare variant level. Further Sanger sequencing only validated five out of 12 rare damaging variants likely involved in HSCR. Hence more improvement at variant detection and sequencing technology is needed to realize the potential of DNA pooling for large-scale resequencing projects.
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http://dx.doi.org/10.1111/ahg.12076DOI Listing
September 2014

Complex transposition repair with aortic arch hypoplasia: a simple technique.

Asian Cardiovasc Thorac Ann 2014 Sep 9;22(7):862-4. Epub 2013 Oct 9.

Department of Surgery, National Hospital of Pediatrics, Hanoi, Vietnam.

A modified technique of interdigitating aortic arch reconstruction was used successfully to treat 8 patients with complex congenital heart disease including transposition of the great arteries, ventricular septal defect, or Taussig-Bing anomalies combined with aortic arch hypoplasia and coarctation of the aorta, without the need for homograft tissue.
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http://dx.doi.org/10.1177/0218492313487357DOI Listing
September 2014

Regulation of the ROS response dynamics and organization to PDGF motile stimuli revealed by single nanoparticle imaging.

Chem Biol 2014 May 10;21(5):647-56. Epub 2014 Apr 10.

Laboratoire d'Optique et Biosciences, Ecole Polytechnique Université Paris Saclay, Inserm U696, CNRS 7645, 91128 Palaiseau, France.

Although reactive oxygen species (ROS) are better known for their harmful effects, more recently, H2O2, one of the ROS, was also found to act as a secondary messenger. However, details of spatiotemporal organization of specific signaling pathways that H2O2 is involved in are currently missing. Here, we use single nanoparticle imaging to measure the local H2O2 concentration and reveal regulation of the ROS response dynamics and organization to platelet-derived growth factor (PDGF) signaling. We demonstrate that H2O2 production is controlled by PDGFR kinase activity and EGFR transactivation, requires a persistent stimulation, and is regulated by membrane receptor diffusion. This temporal filtering is impaired in cancer cells, which may determine their pathological migration. H2O2 subcellular mapping reveals that an external PDGF gradient induces an amplification-free asymmetric H2O2 concentration profile. These results support a general model for the control of signal transduction based only on membrane receptor diffusion and second messenger degradation.
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http://dx.doi.org/10.1016/j.chembiol.2014.02.020DOI Listing
May 2014

One-staged or two-staged surgery for perforated choledochal cyst with bile peritonitis in children? A single center experience with 27 cases.

Pediatr Surg Int 2014 Mar;30(3):287-90

Surgical Department, National Hospital of Pediatrics, 18/879 La Thanh Road, Hanoi, 100000, Vietnam,

Purpose: To report the authors' experience in the management of perforated choledochal cyst with bile peritonitis (PCC) in children.

Methods: Medical records of all children undergoing surgery for PCC at our hospital from May, 2005 to January, 2013 were reviewed.

Results: Twenty seven patients were identified, with a median age of 2 years. The clinical manifestations were abdominal pain (96.3 %), abdominal distention (92.6 %), vomiting (88.9 %), jaundice (74.1 %), fever (70.4 %), acholic stool (51.8 %), abdominal tenderness (92.6 %), peritoneal signs (74.1 %), and palpable mass (18.5 %). Duration of the acute symptoms ranged from 1 to 30 days (median 3 days). Median size of the choledochal cysts was 3 cm (range 1.5-18 cm). Before January 2008, four cases were treated by two-staged surgery and only one case by one-staged surgery. Since then, all remaining 22 cases were treated by the one-staged surgery. There was no anastomotic leakage and all patients were discharged in good health. The mean postoperative stay was 7.6 ± 2.5 days for the one-staged group. No complication was noted at a median follow-up of 24 months.

Conclusions: One-staged definitive repair is feasible, safe and should be the treatment of choice for most cases of childhood PCC in experienced centers.
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http://dx.doi.org/10.1007/s00383-014-3461-6DOI Listing
March 2014

Breastfeeding practices in urban and rural Vietnam.

BMC Public Health 2012 Nov 12;12:964. Epub 2012 Nov 12.

Research Institute for Child Health, National Hospital of Pediatrics, 18/879 La Thanh road, Dong Da district, Hanoi, Vietnam.

Background: The aim of this study was to describe and compare breastfeeding practices in rural and urban areas of Vietnam and to study associations with possibly influencing person and household factors. This type of study has not been conducted in Vietnam before.

Methods: Totally 2,690 children, born from 1st March 2008 to 30th June 2010 in one rural and one urban Health and Demographic Surveillance Site, were followed from birth to the age of 12 months. Information about demography, economy and education for persons and households was obtained from household surveys. Standard statistical methods including survival and regression analyses were used.

Results: Initiation of breastfeeding during the first hour of life was more frequent in the urban area compared to the rural (boys 40% vs. 35%, girls 49% vs. 40%). High birth weight and living in households with large number of assets significantly increased the probability for early initiation of breastfeeding. Exclusive breastfeeding at three months of age was more commonly reported in the rural than in the urban area (boys 58% vs. 46%, girls 65% vs. 53%). The duration of exclusive breastfeeding as well as of any breastfeeding was longer in the rural area than in the urban area (medians for boys 97 days vs. 81 days, for girls 102 days vs. 91 days). The percentages of children with exclusive breastfeeding lasting at least 6 months, as recommended by WHO, were low in both areas. The duration of exclusive breastfeeding was significantly shorter for mothers with three or more antenatal care visits or Caesarean section in both areas. High education level of mothers was associated with longer duration of exclusive breastfeeding in the rural area. No significant associations were found between duration of exclusive breastfeeding and mother's age, household economy indicators or household size.

Conclusion: Intervention programs with the aim to promote breastfeeding are needed. Mothers should particularly be informed about the importance of starting breastfeeding early and to prolong exclusive breastfeeding. In order to reach the WHO recommendation of six months exclusive breastfeeding, we propose an extended maternity leave legislation to at least six months.
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http://dx.doi.org/10.1186/1471-2458-12-964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503814PMC
November 2012

Screening of the RET gene of Vietnamese Hirschsprung patients identifies 2 novel missense mutations.

J Pediatr Surg 2012 Oct;47(10):1859-64

Department of Human Genetics, National Hospital of Pediatrics, Hanoi, Vietnam.

Background/purpose: Hirschsprung disease (HSCR; megacolon, congenital aganglionosis) is a congenital disorder characterized by the absence of ganglion cells along variable segments of the gut. Both rare (RV) and common variants of the RET gene are associated with HSCR. The aim of this study is to assess, for the first time, the variation in the RET gene of Vietnamese HSCR patients.

Methods: We used Sanger sequencing to screen the coding sequence of the RET gene of 97 Vietnamese HSCR patients of Southern Chinese ancestry. The healthy population consisted of 250 Southern Chinese individuals with no diagnosis of HSCR.

Results: We detected 8 heterozygous RVs distributed among 13 patients (13.40%) and that were not present in healthy individuals. Among those variants, there were 2 novel and deleterious (R133C [c.397 C>T]; R144C [c.430 C>T]) missense amino acid substitutions, 2 novel silent variants (P667P [c.2001 A>T]; Y809Y [c.2427 C>T]), and 4 previously described missense substitutions (R114H [c.341 G>A]; V292M [c.874 G>A]; G533S [c.1597 G>A]; R982C [c.2944 C>T]). As expected, the common RET coding sequence variants rs1800858 (A45A [c.135 G>A]) and rs1800861 (L769L [c.2307 T>G]) were highly associated with the disease.

Conclusions: The identification of novel deleterious variants together with the fact RET RVs are virtually unique to HSCR patients indicates that the RET gene is a target for mutations among Hirschsprung patients of any population.
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http://dx.doi.org/10.1016/j.jpedsurg.2012.05.020DOI Listing
October 2012

Novel homozygous p.Y395X mutation in the CYP11B1 gene found in a Vietnamese patient with 11β-hydroxylase deficiency.

Gene 2012 Nov 17;509(2):295-7. Epub 2012 Aug 17.

Institute of Biotechnology, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Hanoi, Vietnam.

Context: The deficiency of steroid 11β-hydroxylase is caused by mutations in the CYP11B1 gene and is the second major form of congenital adrenal hyperplasia associated with hypertension.

Objective: The objective of this study was to screen the CYP11B1 gene for mutations in one Vietnamese male suffering from congenital adrenal hyperplasia.

Patient: The patient (46,XY) had congenital adrenal hyperplasia. The clinical manifestations presented precocious puberty, hyper-pigmentation and high blood pressure at 4 years.

Results: The patient was a homozygous carrier of a novel mutation located in exon 7 containing a premature stop codon instead of tyrosine at 395 (p.Y395X).

Conclusion: We have identified a novel mutant of the CYP11B1 gene in one Vietnamese family associated with phenotypes of congenital adrenal hyperplasia. The mutant gene p.Y395X produces a truncated form of the polypeptide and abolishes the enzyme activities, leading to a severe phenotype of congenital adrenal hyperplasia.
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http://dx.doi.org/10.1016/j.gene.2012.08.009DOI Listing
November 2012

Laparoscopic management of abdominal lymphatic cyst in children.

J Laparoendosc Adv Surg Tech A 2012 Jun 8;22(5):505-7. Epub 2012 May 8.

National Hospital of Pediatrics, Hanoi, Vietnam.

Purpose: The aim of this study is to investigate the feasibility and effectiveness of laparoscopic surgery (LS) in management of abdominal lymphatic cyst (ALC) in children.

Subjects And Methods: Medical records of all patients undergoing LS for ALC at the National Hospital of Pediatrics, Hanoi, Vietnam, from May 2007 to June 2011 were reviewed. For LS, one umbilical port of 10 mm and up to three other 3-5-mm ports were used. Cystic fluid was aspirated prior to removal of the cyst. When intestinal resection was indicated, the mesenteric cyst with the bowel loop was delivered out of the abdomen through a minimally enlarged umbilical incision; resection of the intestinal segment together with the cyst and the bowel anastomosis were both performed extracorporally.

Results: Forty-seven patients were identified, with a mean age of 4.3 ± 3.7 years. The most common symptoms were abdominal pain (72.3%) and abdominal distention (34.0%). Four patients presented with acute abdomen due to infection or hemorrhage of the cyst. Mean size of the ALC was 9.5 ± 5.5 cm (range, 3.4-30 cm). In 12 cases the ALC was omental, and in 35 cases it was mesenteric. Laparoscopic cyst excision was performed in 36 cases (76.6%) versus laparoscopy-assisted bowel resection en bloc with the cyst in 8 cases (17.0%); in 3 patients (6.4%), conversion to open surgery was required. Mean operative time was 79 ± 39 minutes. There were no intra- or postoperative complications. Mean length of hospital stay after laparoscopic management was 3.8 ± 1.6 days. The results of pathologic investigation showed benign cystic lymphangioma in all cases. During follow-up ranging from 1 month to 4 years, recurrence was seen in 1 patient (2.1%) with complex mesenteric cyst. All other patients remained in good health.

Conclusions: Laparoscopic management is safe, feasible, and effective and should be the treatment of choice for most cases of ALC in children.
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http://dx.doi.org/10.1089/lap.2012.0003DOI Listing
June 2012

RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients.

PLoS One 2011 9;6(12):e28986. Epub 2011 Dec 9.

Department of Surgery, University of Hong Kong, Hong Kong, China.

Rare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females; long/total colonic aganglionosis; familial).Here we present the screening for RVs in the RET CDS and intron/exon boundaries of 601 Chinese HSCR patients, the largest number of patients ever reported. We identified 61 different heterozygous RVs (50 novel) distributed among 100 patients (16.64%). Those include 14 silent, 29 missense, 5 nonsense, 4 frame-shifts, and one in-frame amino-acid deletion in the CDS, two splice-site deletions, 4 nucleotide substitutions and a 22-bp deletion in the intron/exon boundaries and 1 single-nucleotide substitution in the 5' untranslated region. Exonic variants were mainly clustered in RET the extracellular domain. RET RVs were more frequent among patients with the most severe phenotype (24% vs. 15% in short-HSCR). Phasing RVs with the RET HSCR-associated haplotype suggests that RVs do not underlie the undisputable association of RET common variants with HSCR. None of the variants were found in 250 Chinese controls.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028986PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235168PMC
April 2012

H5N1-SeroDetect EIA and rapid test: a novel differential diagnostic assay for serodiagnosis of H5N1 infections and surveillance.

J Virol 2011 Dec 28;85(23):12455-63. Epub 2011 Sep 28.

Division of Viral Products, Center for Biologics Evaluation and Research, FDA, Bldg. 29B, Rm. 4NN02, 8800 Rockville Pike, Bethesda, MD 20892, USA.

Continuing evolution of highly pathogenic (HP) H5N1 influenza viruses in wild birds with transmission to domestic poultry and humans poses a pandemic threat. There is an urgent need for a simple and rapid serological diagnostic assay which can differentiate between antibodies to seasonal and H5N1 strains and that could provide surveillance tools not dependent on virus isolation and nucleic acid technologies. Here we describe the establishment of H5N1 SeroDetect enzyme-linked immunosorbent assay (ELISA) and rapid test assays based on three peptides in HA2 (488-516), PB1-F2 (2-75), and M2e (2-24) that are highly conserved within H5N1 strains. These peptides were identified by antibody repertoire analyses of H5N1 influenza survivors in Vietnam using whole-genome-fragment phage display libraries (GFPDLs). To date, both platforms have demonstrated high levels of sensitivity and specificity in detecting H5N1 infections (clade 1 and clade 2.3.4) in Vietnamese patients as early as 7 days and up to several years postinfection. H5N1 virus-uninfected individuals in Vietnam and the United States, including subjects vaccinated with seasonal influenza vaccines or with confirmed seasonal virus infections, did not react in the H5N1-SeroDetect assays. Moreover, sera from individuals vaccinated with H5N1 subunit vaccine with moderate anti-H5N1 neutralizing antibody titers did not react positively in the H5N1-SeroDetect ELISA or rapid test assays. The simple H5N1-SeroDetect ELISA and rapid tests could provide an important tool for large-scale surveillance for potential exposure to HP H5N1 strains in both humans and birds.
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http://dx.doi.org/10.1128/JVI.06023-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209361PMC
December 2011

Genotype X/C recombinant (putative genotype I) of hepatitis B virus is rare in Hanoi, Vietnam--genotypes B4 and C1 predominate.

J Med Virol 2010 Aug;82(8):1327-33

National Hospital of Paediatrics, Hanoi, Vietnam.

There are eight known genotypes of hepatitis B virus, A-H, and several subgenotypes, with rather well-defined geographic distributions. HBV genotypes were evaluated in 153 serum samples from Hanoi, Vietnam. Of the 87 samples that could be genotyped, genotype B was found in 67 (77%) and genotype C in 19 (22%). All genotype C strains were of subgenotype C1, and the majority of genotype B strains were B4, while a few were B2. The genotype X/C recombinant strain, identified previously in Swedish patients of indigenous Vietnamese origin, was found in one sample. This variant, proposed to be classified as genotype I, has been found recently also by others in Vietnam and Laos. The current study indicates that the genotype X/C recombinant may represent approximately 1% of the HBV strains circulating in Vietnam.
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http://dx.doi.org/10.1002/jmv.21775DOI Listing
August 2010

Early and late outcomes of primary laparoscopic endorectal colon pull-through leaving a short rectal seromuscular sleeve for Hirschsprung disease.

J Pediatr Surg 2009 Nov;44(11):2153-5

Department of Surgery, National Hospital of Pediatrics, Hanoi, Vietnam.

Aim: To report early and late outcomes of laparoscopic colon pull-through leaving a short rectal sleeve for Hirschsprung disease.

Methods: Laparoscopic endorectal colon pull-through was performed using 4 ports. The ganglionic and aganglionic segments were initially identified by seromuscular biopsies obtained laparoscopically. The rest of the procedure was carried out according to Georgeson's technique. However, we left a short rectal seromuscular sleeve of 1.5 to 2 cm above the dentate line.

Results: From January 2001 to December 2007, 200 patients were operated upon by the same surgeon. Ages ranged from 14 days to 36 months old. The aganglionic segment was located in the rectum in 112 patients, in the sigmoid colon in 80 children, and in the left colon in 8 patients. The median operating time was 152 minutes. There were no perioperative deaths. Conversion to open surgery was required in four patients. There was minimal blood loss during the surgery. Oral intakes of clear fluid were started 12 hours after surgery and advanced to formula on the second day. In 1 patient, a small intestinal perforation occurred 3 days after surgery, requiring a diverting ileostomy. The mean hospital stay was 6.6 days (range, 4-12 days). Follow-up ranging from 5 to 85 months was obtained in 157 patients; 124 patients (79%) had 1 to 4 defecations a day, 17 (11%) had 5 to 6, and 8 had more than 6. Fecal incontinence occurred in 3 patients (2.0%), constipation in 5 patients (3.0%), and enterocolitis in 15 patients (9.5%). Anastomotic fistula occurred in 2 patients.

Conclusion: Laparoscopic endorectal pull-through leaving a short rectal seromuscular sleeve is a safe and effective procedure for Hirschsprung disease.
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http://dx.doi.org/10.1016/j.jpedsurg.2009.04.029DOI Listing
November 2009

Single europium-doped nanoparticles measure temporal pattern of reactive oxygen species production inside cells.

Nat Nanotechnol 2009 Sep 9;4(9):581-5. Epub 2009 Aug 9.

Laboratoire d'Optique et Biosciences, Ecole Polytechnique, CNRS, INSERM U696, Palaiseau, France.

Low concentrations of reactive oxygen species, notably hydrogen peroxide (H(2)O(2)), mediate various signalling processes in the cell. Production of these signals is highly regulated and a suitable probe is needed to measure these events. Here, we show that a probe based on a single nanoparticle can quantitatively measure transient H(2)O(2) generation in living cells. The Y(0.6)Eu(0.4)VO(4) nanoparticles undergo photoreduction under laser irradiation but re-oxidize in the presence of oxidants, leading to a recovery in luminescence. Our probe can be regenerated and reliably detects intracellular H(2)O(2) with a 30-s temporal resolution and a dynamic range of 1-45 microM. The differences in the timing of intracellular H(2)O(2) production triggered by different signals were also measured using these nanoparticles. Although the probe is not selective towards H(2)O(2), in many signalling processes H(2)O(2) is, however, the dominant oxidant. In conjunction with appropriate controls, this probe is a powerful tool for unravelling pathways that involve reactive oxygen species.
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http://dx.doi.org/10.1038/nnano.2009.200DOI Listing
September 2009

Laparoscopic and transanal approach for rectal atresia: a novel alternative.

J Pediatr Surg 2007 Nov;42(11):E25-7

Department of Surgery, National Hospital of Pediatrics, Hanoi, Vietnam.

Aim: The aim of this study is to present the details and outcomes of laparoscopic and transanal approach in the management of rectal atresia.

Patients: Two female patients with rectal atresia were operated upon using laparoscopic and transanal approach. There were no intraoperative and postoperative complications. Follow-up at 5 and 4 months, respectively, after closure of colostomy has shown both patients with good fecal continence.

Conclusion: Laparoscopic and transanal approach is a novel and good alternative to the current surgical techniques in the management of rectal atresia.
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http://dx.doi.org/10.1016/j.jpedsurg.2007.08.049DOI Listing
November 2007

Thoracoscopic repair for congenital diaphragmatic hernia: lessons from 45 cases.

J Pediatr Surg 2006 Oct;41(10):1713-5

Department of Surgery, National Hospital of Pediatrics, Hanoi, Vietnam.

Purpose: To describe the surgical technique, initial results, and overview indications of thoracoscopic repair of congenital diaphragmatic hernia (CDH).

Materials And Methods: A retrospective review was undertaken of patients with CDH who underwent thoracoscopic repair by the same surgeon from January 2001 to January 2005. Patients underwent surgery under general anesthesia. Reduction of the hernia contents was carried out using 1 optical trocar and 2 operating trocars. Pleural insufflation with carbon dioxide was maintained at a pressure of 2 to 4 mm Hg. The hernia defect was repaired using nonabsorbable interrupted sutures with extracorporeal knots.

Results: There were 45 patients, including 29 boys and 16 girls. Among 19 newborn patients, there were 13 patients younger than 7 days. The other 26 patients were infants and elders. The hernia was located in the left side in 37 patients and in the right side in 8 patients. The mean operative time was 54 minutes. Conversion was required in 4 patients. There were no complications. However, there were 2 postoperative deaths.

Conclusions: Thoracoscopic repair is feasible and safe for children with CDH, including selective newborn. The technique causes minimal trauma, results in good respiratory function, and promotes early recovery.
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http://dx.doi.org/10.1016/j.jpedsurg.2006.05.043DOI Listing
October 2006

Avian influenza A (H5N1) in 10 patients in Vietnam.

N Engl J Med 2004 Mar 25;350(12):1179-88. Epub 2004 Feb 25.

Hospital for Tropical Diseases, Health Service of Ho Chi Minh City, Vietnam.

Background: Recent outbreaks of avian influenza A (H5N1) in poultry throughout Asia have had major economic and health repercussions. Human infections with this virus were identified in Vietnam in January 2004.

Methods: We report the clinical features and preliminary epidemiologic findings among 10 patients with confirmed cases of avian influenza A (H5N1) who presented to hospitals in Ho Chi Minh City and Hanoi, Vietnam, in December 2003 and January 2004.

Results: In all 10 cases, the diagnosis of influenza A (H5N1) was confirmed by means of viral culture or reverse transcriptase-polymerase chain reaction with primers specific for H5 and N1. None of the 10 patients (mean age, 13.7 years) had preexisting medical conditions. Nine of them had a clear history of direct contact with poultry (median time before onset of illness, three days). All patients presented with fever (temperature, 38.5 to 40.0 degrees C), respiratory symptoms, and clinically significant lymphopenia (median lymphocyte count, 700 per cubic millimeter). The median platelet count was 75,500 per cubic millimeter. Seven patients had diarrhea. In all patients, there were marked abnormalities on chest radiography. There was no definitive evidence of human-to-human transmission. Eight patients died, one patient has recovered, and one is recovering.

Conclusions: Influenza A (H5N1) infection, characterized by fever, respiratory symptoms, and lymphopenia, carries a high risk of death. Although in all 10 cases the infection appears to have been acquired directly from infected poultry, the potential exists for genetic reassortment with human influenzaviruses and the evolution of human-to-human transmission. Containment of influenza A (H5N1) in poultry throughout Asia is therefore urgently required.
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http://dx.doi.org/10.1056/NEJMoa040419DOI Listing
March 2004