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Biomedical subjects

V H Nguyen

Publications and source records attributed to V H Nguyen.

At least 19 recordsLinked to original sources
PubMed2003

Gastrointestinal duplications.

BACKGROUND/PURPOSE: The aim of this study was to review the presentations of gastrointestinal duplication (GID) and to assess the influence of prenatal diagnosis on treatment. METHODS: Retrospective review of all GID at 2 pediatric hospitals from 1980-2002 was conducted. RESULTS: Seventy-three patients (M43:F30) were identified: 21 neonates, 28 infants (1 to 24 months), 15 children (1 to 10 years), 9 adolescents (>/=11 years). GID location by frequency was ileum (31.5%), ileocaecal valve (30.2%), duodenum (9.6%), stomach (8.2%), jejunum (8.2%), colon (6.8%), and rectum (5.5%). In neonates and infants, vomiting and distension were the most common presentations. Volvulus, caused by a duplication, occurred in 23.8% of neonates and caused the death of one neonate. Intussusception was identified in 10.9% of patients. In older children and adolescents, pain and vomiting were the most common associations. Six of these patients were being treated for Crohn's disease, with the diagnosis of duplication made at laparotomy. Eighteen patients had a prenatal diagnosis by ultrasound scan, with 77.2% of these asymptomatic after birth. Most prenatal diagnoses occurred after 1991 (77.8%). When comparing an earlier period (1980 to 1991; 29 patients) with the current (1992 to 2002; 44 patients), a greater proportion of the latter patients were asymptomatic (36.4 v 13.8%) and had a lower incidence of complications (volvulus/intussusception). CONCLUSIONS: GID can lead to life-threatening complications. Prenatal diagnosis should lead to expeditious postnatal investigation and treatment before the onset of symptoms or complications. GID in older children can mimic Crohn's disease. Laparoscopy/laparotomy should be considered in patients with atypical Crohn's disease or when the diagnosis of an intraabdominal mass is unclear.

Adolescent↗
PubMed2003

Congenital mid-line cervical cleft: case report and review of literature.

Congenital Mid-line Cervical Cleft (CMCC) is a rare but interesting congenital anomaly of the neck that is frequently misdiagnosed. Much controversy exist regarding its aetiology. Embryologically, the occurrence of CMCC is thought to be due to many hypotheses that include impaired mid-line fusion of the first or second branchial arches, exteriorisation of a thyroglossal duct remnant, and or increased pressure in the cervical area from the pericardial roof in the developing embryo. Histologically, the cleft usually consists of a stratified keratinized squamous epithelium with hyperkeratosis, dermal fibrosis and little or no skin appendages. Associated clinical features could include thyroglossal duct cysts, cleft lip/mandible/sternum, cervical contractures, mandibular spurs, microgenia and or bronchogenic cysts. In this article we present a patient with CMCC. An extensive review of the literature is also included.

Abnormalities, Multiple↗
PubMed2002

A large conductance [Ca(2+)](i)-independent K(+) channel expressed in HaCaT keratinocytes.

Patch-clamp recordings were carried out in the inside-out configuration in human keratinocytes of the cell line HaCaT. Patch pipettes were filled with 150 mM KCl, 1 mM CaCl(2) and 10 mM HEPES. In symmetrical KCl solutions, single channel currents from a large conductance channel (about 170 pS) were measured. Replacement of 120 mM KCl by K-aspartate had only a minor influence on the single channel conductance and on the reversal potential. In intracellular solution in which K(+) has been replaced by Na(+) or NMDG(+), the reversal potential shifted to > + 40 mV indicating K(+) as the main charge carrier. The channels were neither dependent on intracellular Ca(2+) (between 0.8 nM and 10 micro M), ATP (at 0 and 1 mM) nor Mg(2+) (at 0 and 0.5 mM). The mean current showed an outward rectification that can be mainly attributed to the voltage dependence of the open probability. The channels displayed bursting kinetics with a mean open time of about 2 ms and closed times of about 0.2, 2 and 20 ms. The mean open probability was usually low (0.05) but increased occasionally (0.6) mainly due to a lower probability of long closings. We conclude that these K(+) channels contribute to the resting potential of human keratinocytes which may control the Ca(2+) influx and thereby their proliferation and differentiation.

Calcium↗
PubMed2001

Cost-effectiveness of influenza vaccination in high-risk children in Argentina.

OBJECTIVES: our study aimed to evaluate the cost-effectiveness of influenza vaccination in high-risk children in Argentina. METHODS: a decision analysis model was performed, using data from published and unpublished sources, to compare two strategies--to vaccinate or not to vaccinate. We simulated the expected consequences of vaccination on direct medical costs, related to disease management and indirect costs, related to lost parental working days (absenteeism). RESULTS: Using base-case assumptions vaccination of high-risk children aged 6 months to 15 years old, in Argentina (estimated cohort of 1184748) would prevent 207331 cases of influenza, resulting in a reduction of 58052 days of hospitalization and 207331 outpatient visits. Vaccination would lead to net savings of US$ 11894870 per vaccinated cohort (US$ 10.04 per vaccinated child). CONCLUSION: our economic analysis shows that in Argentina, routine vaccination of high-risk children against influenza would be cost saving for society.

Adolescent↗
PubMed2001

A pregnane steroid from Aglaia lawii and structure confirmation of cabraleadiol monoacetate by X-ray crystallography.

The pregnane steroid, (E)-aglawone, along with four known triterpenes, and a known sterol mixture were isolated from the bark of Aglaia lawii (Wight) Saldanha ex Ramamoorty (Meliaceae). The structural determination/identification was accomplished by a combination of 1D- and 2D-NMR spectroscopic techniques. The relative stereochemistry of the known triterpene, 20S,24S-epoxydammarane-3alpha,25-diol acetate, was also unequivocally determined for the first time by X-ray crystallography. The isolates were not active against various human cancer cell lines.

Crystallography, X-Ray↗
PubMed2001

Antimalarial compounds from Rhaphidophora decursiva.

Bioassay-directed fractionation led to the isolation of 14 compounds, six of which possess antimalarial activity, from the dried leaves and stems of Rhaphidophora decursiva. Polysyphorin (1) and rhaphidecurperoxin (6) showed strong activities against Plasmodium falciparum. Rhaphidecursinol A (2), rhaphidecursinol B (3), grandisin (4), and epigrandisin (5) were less active against the same organism. Among the isolates, rhaphidecursinol A (2) and rhaphidecursinol B (3) were determined to be new neolignans, and rhaphidecurperoxin (6) is a new benzoperoxide. Known compounds isolated include polysyphorin (1), grandisin (4), epigrandisin (5), (+)-medioresinol, (-)-pinoresinol, (-)-syringaresinol, (+)-glaberide I, (+)-dehydrovomifoliol, (-)-liliolide, (-)-hydroxydihydrobovolide, and N-butylbenzamide, of which compound 1 appears worthy of further evaluation as an antimalarial agent. Structure elucidation and identification were accomplished by spectroscopic means including 1D and 2D NMR analyses.

Animals↗
PubMed2000

Dorsal and intermediate neuronal cell types of the spinal cord are established by a BMP signaling pathway.

We have studied the role of Bmp signaling in patterning neural tissue through the use of mutants in the zebrafish that disrupt three different components of a Bmp signaling pathway: swirl/bmp2b, snailhouse/bmp7 and somitabun/smad5. We demonstrate that Bmp signaling is essential for the establishment of the prospective neural crest and dorsal sensory Rohon-Beard neurons of the spinal cord. Moreover, Bmp signaling is necessary to limit the number of intermediate-positioned lim1+ interneurons of the spinal cord, as observed by the dramatic expansion of these prospective interneurons in many mutant embryos. Our analysis also suggests a positive role for Bmp signaling in the specification of these interneurons, which is independent of Bmp2b/Swirl activity. We found that a presumptive ventral signal, Hh signaling, acts to restrict the amount of dorsal sensory neurons and trunk neural crest. This restriction appears to occur very early in neural tissue development, likely prior to notochord or floor plate formation. A similar early role for Bmp signaling is suggested in the specification of dorsal neural cell types, since the bmp2b/swirl and bmp7/snailhouse genes are only coexpressed during gastrulation and within the tail bud, and are not found in the dorsal neural tube or overlying epidermal ectoderm. Thus, a gastrula Bmp2b/Swirl and Bmp7/Snailhouse-dependent activity gradient may not only act in the specification of the embryonic dorsoventral axis, but may also function in establishing dorsal and intermediate neuronal cell types of the spinal cord.

Animals↗
PubMed2000

Economic evaluations of influenza vaccination in healthy working-age adults. Employer and society perspective.

OBJECTIVE: To determine what benefits to the employer and to society are associated with influenza (flu) vaccination in healthy adults. DESIGN AND METHODS: We performed a literature review concerning cost-benefit and cost-effectiveness evaluations of influenza vaccination in healthy, working-age adults. Up to the end of 1999, we found 6 published economic evaluations on the use of influenza vaccine in healthy, working-age adults: 3 prospective studies, 1 retrospective evaluation and 2 model-based simulations. Evaluations were performed from the perspective of an employer or society. Costs were reported in the local currency used in the published evaluation, with conversions into US dollars (when not provided in the article), for comparative purposes only, according to the exchange rates of June 8 1998. MAIN OUTCOME MEASURES AND RESULTS: Estimations of the cost-benefit of vaccination, compared with a no vaccination strategy, varied widely from a net loss of $US106.59 per infection averted in one study to savings of varying sizes in the 5 others (savings ranged from $US2.58 per dollar invested to $US46.85 per vaccinee). Studies differed in the definition of illness and the measurement of costs associated with vaccination or illness. CONCLUSIONS: Decision makers have not yet extended existing vaccine recommendations to cover healthy, working-age adults, partly because of the disparity among economic studies in their methods of estimating costs and measuring effects. However, the published studies seem to suggest that influenza vaccination in the healthy, working adult would be a cost-effective health intervention, at least from the perspective of an employer.

Adult↗
PubMed1999

In vitro and in vivo characterisation of [3H]ANSTO-14 binding to the sigma 1 binding sites.

N-(4-phenylbutyl)-3-hydroxy-4-azahexacyclo[5.4.1.0(2,6).0(3, 10).0(5,9) .0(8,11)]dodecane (ANSTO-14) showed the highest activity for the sigma 1 site (Ki = 9.4 nM) and 19-fold sigma 1/sigma 2 selectivity. The present study showed that [3H]ANSTO-14 binds to a single high-affinity site in guinea pig brain membranes with an equilibrium Ki of 8.0 +/- 0.3 nM, in good agreement with the kinetic studies (Kd = 13.3 +/- 5.4 nM, n = 4), and a Bmax of 3.199 +/- 105 fmol/mg protein (n = 4). The in vivo biodistribution of [3H]ANSTO-14 showed a high uptake in the diencephalon. Pretreatment of rats with sigma ligands including (+)-pentazocine (sigma 1), ANSTO-14 (sigma 1), and DTG (sigma 1 and sigma 2) did not significantly reduce radiotracer uptake in the brain, but did in the spleen. A labelled metabolite was found in the liver and brain. Due to its insensitivity to sigma ligands, the accumulation of [3H]ANSTO-14 in the brain indicates high nonspecific binding. Therefore, [3H]ANSTO-14 is a suitable ligand for labelling sigma 1 sites in vitro but is not suitable for brain imaging of sigma binding sites in vivo.

Animals↗
PubMed1999

Combined measurements of hippocampal N-acetyl-aspartate and T2 relaxation time in the evaluation of mesial temporal lobe epilepsy: correlation with clinical severity and memory performances.

PURPOSE: In this study we tried to find a correlation between the clinical severity and memory performances, by comparing proton magnetic resonance (MR) spectroscopy and T2 relaxation time measurements in the hippocampi, in a homogeneous group of 27 patients with unilateral mesial temporal lobe epilepsy with ipsilateral hippocampal sclerosis on MR imaging, with a view to answer the following questions: (a) how sensitive is this approach for the assessment of the apparently normal contralateral hippocampus, (b) do the results relate to the clinical severity, and (c) does it allow evaluation of the degree of hippocampal dysfunction. METHODS: Volume-selective proton MR spectroscopy of the head of both hippocampi was performed at 3 T, by using the PRESS sequence, with an echo time of 135 ms, to estimate NAA/(Cho + Cr) ratios. The relaxation times were measured at 0.28 T, by using a conventional Carr-Purcell-Meiboom-Gill sequence, with a repetition time of 2,000 ms, an echo time of 15 ms, and 48 echoes. RESULTS: The combination of NAA/(Cho + Cr) ratio and T2 relaxation time values was allowed to classify contralateral hippocampus abnormalities in two groups: first, decreased NAA/(Cho + Cr) ratio with strongly increased T2 relaxation time values corresponding to abnormalities observed in sclerotic ipsilateral hippocampi; and second, decreased NAA/(Cho + Cr) ratio with normal or slightly increased T2 relaxation time values. Whereas the NAA/(Cho + Cr) ratio or T2 relaxation time value alone was not correlated with memory performances, their association shows that left hippocampal injury evaluated both by NAA and T2 relaxation time measurements was clearly correlated with verbal memory scores, and right hippocampal injury, with visual memory scores. On the other hand, the maximal seizure frequency reported by the patients was correlated with ipsilateral NAA/(Cho + Cr) ratio and T2 relaxation time values but not with contralateral results. CONCLUSIONS: We showed that the combination of NAA and T2 relaxation time measurements can be used to examine the degree of ipsi- and contralateral hippocampal dysfunction or injuries and their relations with memory performances in the presurgical evaluation of patients.

Adult↗
PubMed1998

Sigma-binding site ligands inhibit K+ currents in rat locus coeruleus neurons in vitro.

Biological actions of novel sigma1- and sigma2-selective binding site ligands (trishomocubanes: 4-azahexacyclo [5.4.1.0.(2,6).0(3,10).0(5,).0(8,11)]dodecanes), and the reference ligands, 1,3-di(2-tolyl)-guanidine (DTG), haloperidol, (+)-pentazocine and dextromethorphan, were studied in rat locus coeruleus neurons using intracellular and whole-cell patch clamp recordings. High concentrations of trishomocubanes produced small inward currents and affected some parameters of action potential waveforms suggesting modest potency to inhibit ionic conductances underlying action potentials. Sigma-ligands produced large inward currents in the presence of mu-opioid, alpha2-adrenoceptor and ORL1 receptor agonists. These reversed polarity near the K+ equilibrium potential, suggesting that sigma-ligands act as ligand activated K+-channel blockers or interfere with the coupling between these receptors and K+-channels. However, no correlation was found between binding affinities at sigma1- or sigma2-binding sites and potency to inhibit K+-currents, suggesting that these effects on K+-channels are not directly related to occupancy of sigma binding sites.

Action Potentials↗
PubMed1998

Ventral and lateral regions of the zebrafish gastrula, including the neural crest progenitors, are established by a bmp2b/swirl pathway of genes.

A bone morphogenetic protein (BMP) signaling pathway is implicated in dorsoventral patterning in Xenopus. Here we show that three genes in the zebrafish, swirl, snailhouse, and somitabun, function as critical components within a BMP pathway to pattern ventral regions of the embryo. The dorsalized mutant phenotypes of these genes can be rescued by overexpression of bmp4, bmp2b, an activated BMP type I receptor, and the downstream functioning Smad1 gene. Consistent with a function as a BMP ligand, swirl functions cell nonautonomously to specify ventral cell fates. Chromosomal mapping of swirl and cDNA sequence analysis demonstrate that swirl is a mutation in the zebrafish bmp2b gene. Interestingly, our analysis suggests that the previously described nonneural/neural ectodermal interaction specifying the neural crest occurs through a patterning function of swirl/bmp2b during gastrulation. We observe a loss in neural crest progenitors in swirl/bmp2b mutant embryos, while somitabun mutants display an opposite, dramatic expansion of the prospective neural crest. Examination of dorsally and ventrally restricted markers during gastrulation reveals a successive reduction and reciprocal expansion in nonneural and neural ectoderm, respectively, in snailhouse, somitabun, and swirl mutant embryos, with swirl/bmp2b mutants exhibiting almost no nonneural ectoderm. Based on the alterations in tissue-specific gene expression, we propose a model whereby swirl/bmp2b acts as a morphogen to specify different cell types along the dorsoventral axis.

Animals↗
PubMed1998

Artemisinin pharmacokinetics in healthy adults after 250, 500 and 1000 mg single oral doses.

Eight healthy male, Vietnamese subjects were administered 1 x 250, 2 x 250, and 4 x 250 mg artemisinin capsules in a cross-over design with randomized sequence with a 7-day washout period between administrations. The inter-individual variability in artemisinin pharmacokinetics was large with parameter coefficient of variation (CV) typically between 50-70%. The parameter with the smallest variability was the elimination half-life (CV approximately equal to 30-40%). Analysis of variance indicated also a large intra-subject variability. (CV, or = 24%) for the dose-normalized area under the plasma concentration-time curve (AUC/dose). The pharmacokinetic results suggested artemisinin to be subject to high pre-systemic extraction. Artemisinin half-life could not predict the extent of in vivo exposure to the drug, there being no correlation between half-life and oral clearance. Artemisinin oral plasma clearance was about 400 L h-1 exhibiting a slight decrease with dose, although the effect was weak. Thus results from studies using different artemisinin doses may, within the studied dose range, be compared without the complication of disproportionate changes in drug exposure with varying dose levels. Half-lives appeared to increase with dose. An observed period effect in the analysis of variance was tentatively associated with time-dependency in artemisinin pharmacokinetics. There was a high correlation between artemisinin plasma concentrations determined at various time-points after drug administration and the AUCs after the 500 and 1000 mg doses, but less so after the 250 mg dose. This may show a tentative approach to assess the systemic exposure of the patients to artemisinin from the determination of artemisinin plasma concentrations in one or two plasma samples only. Artemisinin was well tolerated with no apparent dose or time dependent effects on blood pressure, heart rate or body temperature.

Administration, Oral↗
PubMed1998

Artemisinin kinetics and dynamics during oral and rectal treatment of uncomplicated malaria.

OBJECTIVE: To compare parasite clearance times after oral and rectal administration of artemisinin in adults with uncomplicated malaria and to relate pharmacodynamics with artemisinin kinetics and to disclose any pharmacokinetic changes during treatment. METHODS: Thirty male Vietnamese patients with falciparum malaria were randomized to treatment with 500 mg artemisinin daily by either the oral or rectal route of administration. Parasite densities in capillary blood were determined by microscopy every 4 to 6 hours. Artemisinin plasma concentrations on the first and last day of treatment were determined by HPLC and unbound fractions in plasma were determined by ultrafiltration. RESULTS: Mean parasite clearance times and 95% confidence intervals (95% CI) were 25 (95% CI, 16 to 33) and 29 (95% CI, 23 to 35) hours during oral and rectal treatment, respectively. The bioavailability after rectal relative to oral artemisinin was 30%. Artemisinin areas under the plasma concentration-time curve (AUC) on the fifth (last) day of oral or rectal treatment were 30% (95% CI, 4% to 56%) and 40% (95% CI, -6% to 91%), respectively, of those after the first dose. The fraction unbound in plasma was 15% (95% CI, 12% to 19%), increasing marginally during treatment. No relationship was found between main clinical end points and drug exposure, although indices for the rapidity of response onset were lower after oral treatment and correlated to unbound AUC values (rS = -0.7; p < 0.001). CONCLUSIONS: The similarity in parasite clearance times despite lower drug levels during rectal treatment suggests that initial oral doses may be unnecessarily high. The singular time dependency of artemisinin pharmacokinetics, attributed to autoinduction of drug elimination, has possible implications for combination chemotherapy. Decreasing artemisinin concentrations during treatment may partly explain recrudescences and increase the risk for resistance development.

Administration, Oral↗
PubMed1998

Artemisinin induces omeprazole metabolism in human beings.

OBJECTIVE: This study investigated whether time-dependent artemisinin pharmacokinetics correlated to CYP3A4 or CYP2C19 activity in vivo. METHODS: Artemisinin (two oral doses per day of 250 mg) was given to nine healthy Vietnamese subjects for 7 days (day 1 to day 7). Single 20 mg doses of omeprazole were given orally on day -7, day 1, and day 7. Single doses of artemisinin and omeprazole were given in combination on day 14 after a 6-day washout period. The pharmacokinetics of artemisinin, omeprazole, hydroxyomeprazole, and omeprazole sulfone were evaluated on days -7, 1, 7, and 14. On the same days urine was collected for the determination of 6beta-hydroxycortisol and cortisol excretion. RESULTS: Areas under plasma concentration-time curves (AUC) for artemisinin and omeprazole decreased on day 7 to 20% (95% confidence intervals, 13%, 28%) and 35% (25%, 46%), respectively, compared with values on day 1. AUC ratios for hydroxyomeprazole/omeprazole increased 2.2-fold (1.7, 2.7) on day 7 compared with values on day 1. All values were normalized at day 14. There were no significant changes in the omeprazole sulfone/omeprazole ratio or in the 6beta-hydroxycortisol/cortisol ratio between the study days. In one subject found to have poor CYP2C19 metabolization, the elimination of omeprazole increased after artemisinin exposure, with no change in the hydroxyomeprazole/omeprazole AUC ratio. CONCLUSION: Artemisinin did not alter CYP3A4 activity, whereas an increase in CYP2C19 activity was observed. The increased elimination of omeprazole in both poor and extensive CYP2C19 metabolizers suggests artemisinin induces both CYP2C19 and another enzyme.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Carbamazepine intoxication with negative myoclonus after the addition of clobazam.

We report a case a carbamazepine (CBZ) intoxication with negative myoclonus that occurred 4 weeks after clobazam (CLB) had been added to a stable regimen of CBZ and topiramate (TPM). Both CBZ and CBZ-epoxide (CBZ-E) blood levels were elevated, and the symptoms resolved quickly when CBZ dosage was reduced and CLB discontinued. CLB was reintroduced a year later with the patient's consent, and the time course of the interaction was studied: CBZ and CBZ-E levels increased slowly over 12 days. The interaction is thus probably related to the progressive increase in Nor-CLB.

Aged↗