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Biomedical subjects

T H Nguyen

Publications and source records attributed to T H Nguyen.

At least 73 records · Page 4Linked to original sources
PubMed1997

Overexpression of endothelin-1 mRNA and protein in portal hypertensive gastric mucosa of rats: a key to increased susceptibility to damage?

BACKGROUND: Portal hypertension predisposes gastric mucosa to increased injury by various noxious factors. Because endothelin-1 (ET-1) is a potent vasoconstrictor that enhances gastric mucosal injury, we examined ET-1 expression in the portal hypertensive (PHT) gastric mucosa and its possible role in increased mucosal susceptibility to damage. METHODS: In gastric specimens of PHT or sham-operated rats, ET-1 mRNA expression was studied by S1-nuclease protection assay and ET-1 protein by enzyme immunoassay and immunostaining. We also determined the extent of ethanol-induced gastric mucosal necrosis in PHT and sham-operated rats after administering either a placebo or FR 139317, a selective ETA receptor antagonist. RESULTS: In PHT stomachs ET-1 mRNA expression and protein concentration were significantly increased compared with sham-operated controls: mRNA expression (ET-1/glyceraldehyde-3-phosphate-dehydrogenase ratio), 0.54 +/- 0.18 versus 0.30 +/- 0.08; protein concentration, 7.36 +/- 2.21 pg/mg versus 3.93 +/- 0.40 pg/mg, respectively; both p < 0.01. Immunofluorescence signal of ET-1 protein was predominantly localized to endothelia of gastric mucosal and submucosal vessels. In PHT stomachs FR 139317 significantly reduced mucosal necrosis (percentage of necrotic area, from 24.9 +/- 5.9% to 10.8 +/- 4.0%; p < 0.01), although it had no effect on sham-operated controls. CONCLUSIONS: Portal hypertension activates the ET-1 gene with overexpression of ET-1 protein in the gastric mucosa. Protection of PHT gastric mucosa by ETA receptor antagonist against damage indicates that overexpression of ET-1 plays an important role in increased susceptibility of PHT gastric mucosa to injury.

Animals↗
PubMed1997

The effect of benzyl alcohol on recombinant human interferon-gamma.

PURPOSE: The goal of this study was to investigate the conformational change and aggregation of recombinant human interferon-gamma (rhIFN-gamma) as a result of interaction between benzyl alcohol and the protein. The effects of buffer concentration, buffer species, ionic strength, rhIFN-gamma and benzyl alcohol concentrations on the dynamics of the interaction in liquid formulations were also examined. METHODS: The effect of benzyl alcohol on the secondary and tertiary structure of rhIFN-gamma in succinate and acetate buffers was studied using far-UV and near-UV circular dichroism spectrophotometry, respectively. Dynamic light scattering was employed to detect aggregate formation due to the interaction of benzyl alcohol with rhIFN-gamma. RESULTS: The addition of benzyl alcohol at 0.9% (w/v) in various liquid rhIFN-gamma formulations induced changes in circular dichroism (CD) spectra of the protein in the near-UV region, while the CD spectra in the far-UV region remained unaltered. There were gradual decreases in ellipticity with time throughout the near-UV CD spectra. The decreases in near-UV ellipticity induced by benzyl alcohol were accompanied by the formation of high molecular weight aggregates as measured by dynamic light scattering. Loss in near-UV ellipticity was accelerated at lower protein concentration and by increasing buffer or benzyl alcohol concentration. It was also faster in succinate than in acetate buffer. Formulation ionic strength did not affect the CD spectral changes in both the near- and far-UV regions. CONCLUSIONS: Interaction between benzyl alcohol and rhIFN-gamma is formulation dependent. Protein concentration, buffer species, buffer concentration, and preservative concentration play a significant role in determining the extent of the interaction and consequently the stability of the product.

Benzyl Alcohol↗
PubMed1997

Two major strains of type 1 wild poliovirus circulating in Indochina.

Two hundred ninety-four isolates from 329 patients with acute flaccid paralysis in Cambodia and Vietnam during 1992-1995 were identified as type 1 wild polioviruses. Among these isolates, 85 were selected as geographic representatives and were examined by determining the nucleotide sequences of their genome in the VP1 region. The phylogenic analysis revealed that all of the isolates examined were classified into groups A and B. Isolates belonging to group A had been found only in northern Vietnam until 1993 but not in 1994 and 1995. Group B isolates were located in both northern and southern Vietnam and Cambodia. In 1994 and 1995, however, only group B isolates were found in the Mekong Delta area in southern Vietnam and Cambodia. Isolates of groups A and B were genetically different from strains previously isolated in other Asian countries. One of the two indigenous wild polioviruses still remains to be eliminated in this area.

Antigens, Viral↗
PubMed1997

Nucleotide sequence variation of human T-lymphotropic virus type II in Vietnam.

A high rate of human T-lymphotropic virus type II (HTLV-II) infection has been documented in intravenous drug abusers (IVDAs) in South Vietnam. We have investigated the molecular characteristics of the virus and have shown that one HTLV-II subtype is predominant in Ho Chi Minh City. This molecular subtype, HTLV-IIb, was identified in a number of South Vietnamese by nucleotide sequence analysis of the long terminal repeat (LTR) region. HTLV-IIa was not found. These findings suggest that HTLV-IIb is endemic in IVDAs in South Vietnam, although IVDAs in urban areas in North America are predominantly infected with HTLV-IIa.

Adult↗
PubMed1997

Impact of prenatal care on perinatal mortality.

This study aimed to estimate the perinatal mortality rate (PMR) in Ho Chi Minh City, Vietnam, and to assess the association between perinatal death (PD) and prenatal care (PC). During January 1st to December 31st, 1992, among 4,809 births ascertained from 22 communes randomly selected in two areas, urban and rural, of Ho Chi Minh City, 48 still births and 66 early neonatal deaths were recorded, resulting in a weighted PMR of 25 (95% confidence interval: 20-29) per thousand. Major causes of PD were prematurity 33%, congenital malformation 15%, perinatal asphyxia 12%, perinatal infection 11%, birth injury 4%, others 8% and unknown 16%. From the whole sample, a nested case-control study was conducted on 103 cases (all the mothers whose infants died) and 309 controls (selected among the mothers of surviving infants) to assess the relationship between PD and prenatal care (PC). During unconditional logistic regression, starting prenatal care (PC) within the 1st trimester was associated with a lower risk of PD, giving an odds ratio of 0.11 (95% CI: 0.02-0.61), whereas having 4 to 8 visits gave an odds ration of 0.15 (95% CI: 0.03-0.67). It is concluded that early onset of prenatal care and having four to eight visits provide significant protection against perinatal mortality.

Adolescent↗
PubMed1997

[Neovascularization of pre-formed tissue flaps in relation to arteriovenous blood flow of the implanted vascular pedicle. Experimental study in the rabbit].

In 45 Chinchilla-Bastard rabbits, a skeletonised arterio-venous pedicle was implanted on the subsurface of a 15 x 8 cm abdominal skinflap to create a neovascularised axial prefabricated flap. In order to evaluate the potency of neovascularisation in relation to the blood flow of the pedicle, we compared minimal blood flow by distal ligation (model 1) with maximal blood flow by distal microvascular arteriovenous shunt anastomoses (model 2) of the implanted vascular pedicle. The results show that 8 and 12 days after pedicle implantation, tissue flap perfusion in model 2 is significantly earlier and better in comparison to model 1.

Anastomosis, Surgical↗
PubMed1996

Clearance kinetics of parasites and pigment-containing leukocytes in severe malaria.

In tropical areas, where unsupervised use of antimalarial drugs is common, patients with an illness consistent clinically with severe malaria but with negative blood smears pose a management dilemma. Malaria pigment is evident in peripheral blood leukocytes in greater than 90% of patients with severe malaria. To characterize the clearance kinetics of parasitized erythrocytes and malaria pigment-containing leukocytes, sequential peripheral blood and intradermal smears were assessed in 27 adult Vietnamese patients with severe falciparum malaria. The clearance of parasitized erythrocytes and pigment-containing monocytes (PCMs) followed first order kinetics. The elimination of pigment-containing neutrophils (PCNs) was first order initially, but deviated from this when counts were low. Clearance of peripheral blood PCMs (median clearance time, 216 hours; range, 84 to 492 hours) was significantly slower than that of parasitized erythrocytes (median, 96 hours; range, 36 to 168 hours) or PCNs (median, 72 hours; range, 0 to 168 hours; P < .0001). Intradermal PCM clearance times were the longest of all (median, 12 days; range, 6 to 23 days; significantly longer than peripheral blood PCM clearance, P < .001). Twenty-one (88%) patients still had signs, symptoms, or laboratory features of severe malaria after parasite clearance but before phagocyte pigment clearance. Sixteen of the 23 surviving patients (70%; 95% confidence interval, 50% to 87%) still had intraleukocytic malaria pigment on peripheral blood films 72 hours after parasite clearance. Thus, by determining the distribution of malaria pigment in peripheral blood and intradermal phagocytes, the time since effective antimalarial treatment started can be estimated. Microscopy for intraleukocytic pigment is valuable in the differential diagnosis of severe febrile illnesses in malarious areas where uncontrolled use of antimalarial drugs is widespread.

Adult↗
PubMed1996

Time-resolved immunofluorometric assay of pregnancy-associated plasma protein A in maternal serum screening for Down's syndrome in first trimester of pregnancy.

A low maternal serum concentration of pregnancy associated plasma protein-A (MS-PAPP-A) in the first trimester has been suggested as a marker for the presence of a Down's syndrome (DS) fetus. We developed a time-resolved immunofluorometric assay (TrIFMA) for PAPP-A with a sensitivity < 3.9 mIU/l. In the 7-12 gestational weeks interval the median multiples of the median (MoM) was 0.57 (95%-confidence interval; 0.47-0.99) in DS pregnancies (n = 29) and lower than in controls (n = 223) (P < 0.005). The efficiency of MS-PAPP-A alone was evaluated using empirical receiver-operator-characteristics (ROC) and a sensitivity of about 25% was found for a false-positive rate of about 10% in the 7-12 gestational weeks interval. In parameterized ROC analysis a sensitivity of 9% was found for a false-positive rate of 5%. The TrIFMA PAPP-A assay seems to fulfil the quality criteria for an assay to be used in large-scale serum screening for Down's syndrome.

Down Syndrome↗
PubMed1996

Post-malaria neurological syndrome.

BACKGROUND: Neurological signs and symptoms are common in malaria, but observations in Vietnam and Thailand have pointed to a discrete transient neurological syndrome after recovery from severe infections. METHODS: A prospective study of the post-malaria neurological syndrome (PMNS) was conducted at two centres in Vietnam over four years. Criteria for inclusion were recent symptomatic malaria infection with parasites cleared from blood (and in cases of cerebral malaria full recovery of consciousness), and development of neurological or psychiatric symptoms within two months after the acute illness. Half of the patients with severe falciparum malaria had been taking part in a randomised trial of antimalarials. FINDINGS: Of 18,124 patients with falciparum malaria treated (1176 of whom had severe infections) 19 adults and three children had subsequent PMNS; in one patient it followed uncomplicated malaria and in 21 it followed severe malaria. The overall incidence (95% confidence interval) of PMNS after falciparum malaria at the main study centre was 1.2 per 1000 (0.7 to 1.8 per 1000) and relative risk (95% CI) for developing PMNS after severe versus uncomplicated falciparum malaria was 299 (40 to 2223). 13 patients had an acute confusional state or psychosis, six had one or more generalised convulsions, two had generalised convulsions followed by a long period of acute confusion, and one developed a fine tremor. At the time of PMNS diagnosis all patients were aparasitaemic. The syndrome was self-limiting, median duration 60 h (range 24-240). PMNS was associated with the use of oral mefloquine. In the randomised trial 4.4% (10/228) of patients with severe malaria who received mefloquine after parenteral treatment developed PMNS compared with 0.5% (1/210) of those who received quinine; relative risk 9.2 (95% CI 1.2 to 71.3, p = 0.012). INTERPRETATION: Mefloquine is not the only risk factor for PMNS but it is a strong one. Where an effective alternative drug is available, mefloquine should not be used after treatment of severe malaria.

Adolescent↗
PubMed1996

[Vesico-amniotic shunt-therapy in fetal obstructive uropathy].

Due to the widespread use of obstetric ultrasound an increasing number of congenital malformations are diagnosed prenatally. Some of these can be treated in utero. A 17 week-old fetus with a posterior urethral valve was diagnosed due to a dilated bladder, bilateral hydronephrosis and oligohydramnios. An ultrasonically guided vesicoamniotic shunt was successfully placed in utero at 24 weeks of gestation in order to prevent development of dysplastic kidneys and hypoplastic lungs. Transurethral valve resection was performed five months postnatally. The one year-old infant is now well and has one normally functioning kidney.

Abnormalities, Multiple↗
PubMed1996

A controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria.

BACKGROUND: Artemisinin (qinghaosu) and its derivatives are rapidly effective antimalarial drugs derived from a Chinese plant. Preliminary studies suggest that these drugs may be more effective than quinine in the treatment of severe malaria. We studied artemether in Vietnam, where Plasmodium falciparum has reduced sensitivity to quinine. METHODS: We conducted a randomized, double-blind trial in 560 adults with severe falciparum malaria. Two hundred seventy-six received intramuscular quinine dihydrochloride (20 mg per kilogram of body weight followed by 10 mg per kilogram every eight hours), and 284 received intramuscular artemether (4 mg per kilogram followed by 2 mg per kilogram every eight hours). Both drugs were given for a minimum of 72 hours. RESULTS: There were 36 deaths in the artemether group (13 percent) and 47 in the quinine group (17 percent; P = 0.16; relative risk of death in the patients given artemether, 0.74; 95 percent confidence interval, 0.5 to 1.11). The parasites were cleared more quickly from the blood in the artemether group (mean, 72 vs. 90 hours; P < 0.001); however, in this group fever resolved more slowly (127 vs. 90 hours, P < 0.001), the time to recovery from coma was longer (66 vs. 48 hours, P = 0.003), and the hospitalization was longer (288 vs. 240 hours, P = 0.005). Quinine treatment was associated with a higher risk of hypoglycemia (relative risk, 2.7; 95 percent confidence interval, 1.7 to 4.4; P < 0.001), but there were no other serious side effects in either group. CONCLUSIONS: Artemether is a satisfactory alternative to quinine for the treatment of severe malaria in adults.

Adolescent↗
PubMed1996

Flux measurements across Caco-2 monolayers may predict transport in human large intestinal tissue.

Confluent monolayers of Caco-2 cells, a human colonic carcinoma cell line, have been used extensively to predict intestinal absorption. A direct comparison of uptake characteristics, however, between cell monolayers and human tissue is missing in the literature. We have determined the flux for a series of small organic molecules, peptide and protein therapeutics, across Caco-2 monolayers and normal human colonic and rectal tissue in vitro to assess whether or not a predictive correlation of transport exists. Caco-2 cells were grown to confluency of Snapwells, and human tissue was obtained from patients undergoing surgery for localized tumors. Mucosa-serosa fluxes were measured by HPLC for small molecules and peptides, and proteins were analyzed by ELISA or RIA. Permeability coefficients were calculated from flux data and compared with previously published coefficients where possible. The permeability coefficients for the examined molecules were of a similar magnitude across Caco-2 cell monolayers and human tissues, ranging from 10(-7) to 10(-5) cm/s. A best-fit analysis of a log-log plot of transport measurements obtained in these two systems gave a good correlation (R2 = 0.991). From this limited data set it appears that uptake characteristics for human colon and rectum are similar to those of Caco-2 cell monolayers. Thus, flux measurements across Caco-2 monolayers may be predictive for permeabilities of human colon and rectum for different classes of therapeutics.

Atenolol↗
PubMed1996

Inhibitory effect of sugars and polyols on the metal-catalyzed oxidation of human relaxin.

Previously, our laboratory (Li, S.; et al. Biochemistry 1995, 34, 5762-5772) showed that the oxidation of recombinant human relaxin (Rix) could be induced by ascorbic acid (AsA)/Cu(II), a system used for the metal-catalyzed generation of reactive oxygen species. In this study, we observed that this oxidation could be inhibited by high concentrations of mannitol and other sugars and polyols, such as ethylene glycol, glycerol, glucose, and dextran. Similar protective effects with high concentrations of mannitol were also observed in the AsA/CuCl2-induced oxidation of Gly-Met-Gly and Gly-His-Gly. In contrast, (carboxymethyl)cellulose had no protective effect on the metal-catalyzed oxidation of Rix. These results, together with results from deuterium isotope experiments and spectroscopic experiments, suggest that the inhibitory effect of polyols and sugars is probably due to the complexation of transition metal ions rather than a hydroxyl radical scavenging mechanism. However, dextran, a high molecular weight polysaccharide, might function as a hydroxyl radical scavenger to protect Rix from the metal-catalyzed oxidation.

Ascorbic Acid↗
PubMed1996

Effects of reducing sugars on the chemical stability of human relaxin in the lyophilized state.

Sugars and polyols have been used routinely with lyophilized proteins and peptides as bulking agents, cryoprotectants, and lyoprotectants. However, reducing sugars may present a problem as excipients since they are potentially reactive with proteins. In this stability study of recombinant human relaxin (Rix) with various sugars as excipients in lyophilized formulations, we observed rapid covalent modifications of the protein in the presence of glucose. Analysis of the protein by LC/MS and tryptic mapping indicated two major degradation pathways. Covalent adducts of glucose with amino groups on the side chains of the protein (i.e., Lys and Arg) formed via the Maillard reaction. In addition, a significant amount of Ser cleavage from the C-terminal of the B-chain of relaxin was also identified when glucose was used as the excipient. It was observed that the latter reaction occurred to a greater extent in the solid state than in solution. We proposed a mechanism for this reaction involving an initial reaction of the Ser hydroxyl group with glucose followed by subsequent hydrolysis of the Trp-Ser amide bond via a cyclic intermediate. In contrast to glucose, mannitol (polyhydric alcohol) and trehalose (nonreducing sugar) produced stable, lyophilized formulations of Rix.

Amino Acid Sequence↗
PubMed1996

Isolated amyloidosis of the colon.

A 46-year-old man was seen with a 2-month history of crampy abdominal pain and recent onset of hematochezia. Colonoscopic examination revealed a semiannular mass lesion in the descending colon which was thought to represent a near-obstructing neoplasm. A partial colon resection was performed. Gross inspection revealed a segment of bowel with focally necrotic mucosa but no mass lesion. Microscopic examination revealed deposits of amyloid infiltrating the muscularis propria, submucosal vessel walls, and lamina propria, with focal ischemic necrosis of mucosa. Special stains were positive for light chains, indicating primary amyloidosis. Follow-up studies for multiple myeloma and inflammatory disorders gave negative results. A diagnosis of isolated amyloidosis of the colon was rendered. Two months after surgery, the patient had a recurrence of symptoms and colon biopsy specimens revealed amyloidosis. The patient was given colchicine, with subjective and objective improvement. The various types of amyloidosis are discussed.

Abdominal Pain↗
PubMed1996

Limited value of routine followup CT scans in nonoperative management of blunt liver and splenic injuries.

The objective was to determine the utility of a second CT scan in nonoperative management of blunt liver and splenic trauma. The design was a retrospective review of consecutive cases over a 2-year period in two trauma centers. Subjects were 152 patients with blunt abdominal trauma and isolated injuries to liver and/or spleen. Thirty patients received immediate laparotomy, whereas 122 patients (80%) underwent CT scanning that showed splenic (n = 64), liver (n = 44), or combined (n = 14) injuries. Nonoperative management was undertaken in 99 of the 122 (81% of the patients who received CT scans; 65% of the overall series) and was ultimately successful in 94 (95%). Second CT scans were used in 26 patients (26%), one of whom received laparotomy for drainage of a bile leak and three for ongoing bleeding. None of the followup scans showed major progression of injury, and scan findings did not influence decisions for operation in any patients. Routine followup CT scanning is not a justifiable component of nonoperative management protocols for blunt liver and splenic injuries.

Adolescent↗