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Biomedical subjects

T T Nguyen

Publications and source records attributed to T T Nguyen.

270 records · Page 15Linked to original sources
PubMedDate not supplied

Comparison of artemisinin suppositories, intramuscular artesunate and intravenous quinine for the treatment of severe childhood malaria.

Severe malaria remains a major cause of mortality and morbidity for children living in many tropical regions. With the emergence of strains of Plasmodium falciparum resistant to both chloroquine and quinine, alternative antimalarial agents are required. The artemisinin group of compounds are rapidly effective in severe disease when given by intramuscular or intravenous injection. However, these routes of administration are not always available in rural areas. In an open, randomized comparison 109 Vietnamese children, aged between 3 months and 14 years, with severe P.falciparum malaria, were allocated at random to receive artemisinin suppositories followed by mefloquine (n = 37), intramuscular artesunate followed by mefloquine (n = 37), or intravenous quinine followed by pyrimethamine/sulfadoxine (n = 35). There were 9 deaths: 2 artemisinin, 4 artesunate and 5 quinine-treated children. There was no difference in fever clearance time, coma recovery, or length of hospital stay among the 3 groups. However, parasite clearance times were significantly faster in artemisinin and artesunate-treated patients than in those who received quinine (P < 0.0001). Both artemisinin and artesunate were very well tolerated, but children receiving these drugs had lower peripheral reticulocyte counts by day 5 of treatment than those in the quinine group (P = 0.011). No other adverse effect or toxicity was found. There was no treatment failure in these 2 groups, but 4 patients in the quinine group failed to clear their parasites within 7 d of starting treatment and required alternative antimalarial therapy. Artemisinin suppositories are easy to administer, cheap, and very effective for treating children with severe malaria. In rural areas where medical facilities are lacking these drugs will allow antimalarial therapy to be instituted earlier in the course of the disease and may therefore save lives.

Adolescent↗
PubMedDate not supplied

Short courses of ofloxacin for the treatment of enteric fever.

Typhoid fever continues to be a major public health problem in tropical countries, exacerbated in recent years by the spread of multi-drug resistant strains of Salmonella typhi. Short treatment courses of fluoroquinolones are effective, and have the advantage of reduced cost and increased compliance, but the optimal length of treatment is unknown. In an open, randomized comparison, 107 adults with uncomplicated enteric fever (95 of whom had positive blood cultures for S. typhi and 5 for S. paratyphi) were treated with oral ofloxacin, 15 mg/kg/d for 2 d or 10 mg/kg/d for 3 d. Mean fever clearance times were the same in the 2 treatment groups (97 h). There were 7 treatment failures, one in the 2 d group and 6 in the 3 d group (P = 0.07). Three of the 5 patients infected with nalidixic acid resistant strains of S. typhi had treatment failures, compared with 4 of 90 with nalidixic acid sensitive isolates (P < 0.0001; relative risk 13.5, 95% confidence interval 4.1-43%). Treatment with ofloxacin for 2 or 3 d is equally effective in adults with uncomplicated enteric fever caused by nalidixic acid sensitive strains of S. typhi. The epidemiology and management of nalidixic acid resistent typhoid needs further investigation.

Adult↗
PubMedDate not supplied

Pharmacokinetics of oral artesunate in children with moderately severe Plasmodium falciparum malaria.

The pharmacokinetic properties of oral artesunate (3 mg/kg) were determined in 10 Vietnamese children, aged from 6 to 15 years, with acute falciparum malaria of moderate severity. Plasma concentrations were measured using a bioassay and expressed in terms of antimalarial activity equivalent to dihydroartemisinin, the principal biologically active metabolite. Oral artesunate was absorbed rapidly with a mean time to peak plasma bioactivity of 1.7 h (95% confidence interval [95% CI] 0.8-2.6). There was wide variation in peak plasma concentrations with a mean value equivalent to 664 ng of dihydroartemisinin/mL (95% CI 387-9410, range 179-1395) and a four-fold variation in the area under the plasma concentration-time curves. Elimination from plasma was rapid with a mean (95% CI) half-life of 1.0 h (95% CI 0.8-1.4). Plasma antimalarial levels were below the limit of detection in all cases by 12 h, despite the relatively high dose of artesunate used. Oral artesunate is rapidly absorbed and rapidly eliminated in children with moderately severe malaria but there is considerable variation between individuals.

Administration, Oral↗
PubMedDate not supplied

Epidural anesthesia for extracorporeal shock wave lithotripsy in an achondroplastic dwarf.

BACKGROUND AND OBJECTIVES: A 66-year-old achondroplastic male dwarf with right ureteral stones presented for outpatient extracorporeal shock wave lithotripsy under epidural anesthesia. METHODS: The patient had marked lumbar lordosis and mild thoracic kyphosis. Although the epidural space was located easily at the L2-3 interspace on the first attempt, the catheter could not be advanced beyond the Tuohy needle. On the second attempt, the epidural space was located easily at the L1-2 interspace, and the catheter was advanced without difficulty. RESULTS: A sensory block to the T2 level developed after administration of 2 mL of lidocaine 1.5% with epinephrine 1:200,000 and 9 mL of lidocaine 2.0% with epinephrine 1:200,000. Aside from a short period of mild, asymptomatic hypotension, the patient's intraoperative and postoperative courses were unremarkable. CONCLUSIONS: This case report and the available literature support the feasibility of epidural anesthesia in achondroplastic patients. Careful titration of the local anesthetic dose is recommended since achondroplastic patients may have extensive spread of epidural anesthesia.

Achondroplasia↗
PubMedDate not supplied

Fluoranthene metabolism: human and rat liver microsomes display different stereoselective formation of the trans-2,3-dihydrodiol.

The metabolism of the environmental carcinogen fluoroanthene by human liver microsomes was compared to that by liver microsomes from rats treated with Aroclor 1254. Although the human-derived system gave primarily one product, similar metabolites were noted from each system. Enantiomers of the major metabolic product, in both cases the trans-2,3-dihydrodiol, were separated by chiral stationary-phase chromatography. Absolute configurations were assigned by application of the benzoate exciton chirality rules to the CD spectra of the 4-(dimethylamino)benzoyl esters. Liver microsomes from Aroclor 1254-treated rats produced the R,R enantiomer of the diol in 75-78% enantiomeric excess, while human liver microsomes produced this enantiomer in only 6-12% excess. The activities of these enantiomers were compared in Salmonella typhimurium strain TM677 mutagenicity assays employing the 9000g supernatant of Aroclor 1254-induced rat liver homogenates. Both the syn- and anti-2,3-dihydrodiol 1,10b-epoxides, which had only been inferred to be metabolites in previous studies, were isolated from the microsomal incubations by preparative reverse-phase HPLC. The evident exceptional aqueous stabilities of these diol epoxides were further examined by half-life determination experiments. Their tetrahydrotetrol hydrolysis products were also noted in the metabolite HPLC profiles. The structures of the tetrahydrotetrols were confirmed by total synthesis.

Animals↗
PubMedDate not supplied

Mutagenic decomposition products of nitrosated 4-chloroindoles.

4-Chloro-6-methoxyindole, a constituent of fava beans, forms a potent direct-acting mutagen, 4-chloro-6-methoxy-2-hydroxy-1-nitrosoindolin-3-one oxime, when nitrosated. In order to better understand the properties of this mutagen, we have studied a readily-available analog, 4-chloro-2-hydroxy-1-nitrosoindolin-3-one oxime, prepared by nitrosation of 4-chloroindole. This analog is also mutagenic, and both mutagens decompose rapidly at neutral or higher pH to yield in each case a new, less potent mutagen which then reacts further to form a nonmutagenic final product. The two products arising from 4-chloro-2-hydroxy-1-nitrosoindolin-3-one oxime, on the basis of comparison of spectroscopic and chromatographic evidence with that from authentic standards, are 4-chloro-N-nitrosodioxindole and 4-chloroisatin; those arising from 4-chloro-6-methoxy-2-hydroxy-1-nitrosoindolin-3-one oxime appear to be the corresponding 6-methoxy analogs. The interplay of these pathways with respect to net biological activity, especially under gastric conditions, remains to be described.

Chromatography, Gas↗
PubMedDate not supplied

Free radical activity and loss of plasma antioxidants, vitamin E, and sulfhydryl groups in patients with burns: the 1993 Moyer Award.

This study examines the relationship of burn injury and plasma levels of conjugated dienes, total sulfhydryl groups, and vitamin E in patients with thermal injuries. Plasma neopterin levels were determined as an index of macrophage activity and serine elastase as an index of polymorphonuclear cell activation. Thirteen patients with burns, six survivors and seven nonsurvivors, were studied for the first 4 days, then every other day until postburn day 14. Twelve healthy volunteers served as the control group. Survivors had 56% +/- 4% total body surface area burned, and nonsurvivors had 63.9% +/- % total body surface area burned. The patients with burns, compared with the control group, showed elevated plasma levels of the lipid peroxidation products conjugated dienes (0.767 +/- 0.045 vs 0.269 +/- 0.013 Abs at 233 nm) and reduced levels of the natural scavengers of free radicals, vitamin E (196.2 +/- 12.6 vs 841.1 +/- 22.7 micrograms/dl) and total sulfhydryl groups (54.0 +/- 0.4 vs 15.8 +/- 1.0 mumol/dl). The total sulfhydryl groups/conjugated dienes ratio fell at a greater rate (9.8% +/- 3.2% vs 3.2% +/- 0.7%/day) in nonsurvivors than in survivors (p < 0.05 by Mann-Whitney). The levels of elastase were slightly elevated in the patients with burns, but there was no difference between survivors and nonsurvivors. Normal neopterin levels are 3 to 10 nm/L; peak levels were 119 +/- 48 nm/L in nonsurvivors and 37.4 +/- 10 nm/L in survivors. Patients with burns demonstrated evidence of increased oxygen free radical activity and activation of polymorphonuclear cell and macrophages. Nonsurvivors demonstrated increased consumption of antioxidants compared with survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Risk stratification prior to vascular surgery: does the location of a dipyridamole thallium scintigram defect provide prognostic information?

BACKGROUND: While the value of myocardial scintigraphy using dipyridamole thallium is accepted for risk assessment prior to vascular surgery, it is unknown whether the location of the thallium abnormalities provides prognostic information. METHODS: Records from 435 consecutive patients scheduled for vascular surgery were reviewed and patients with dipyridamole thallium abnormalities involving the anterior distribution (ANTERIOR n = 62), or inferior or inferolateral distribution (INFERIOR n = 105) were assessed for cardiac complications of surgery (death, myocardial infarction, unstable angina or ischemic congestive heart failure). RESULTS: Patients with a normal dipyridamole thallium scintigraphy had few surgical cardiac complications: 2/86 (2%). Patients with an ANTERIOR dipyridamole thallium defect had a 12% incidence of surgical cardiac complications (7/57) without any cardiac deaths, while patients with an INFERIOR dipyridamole thallium defect had a similar incidence of surgical cardiac complications, 18% (18/100; p = 0.65 vs. ANTERIOR) including 4 cardiac deaths. CONCLUSIONS: Significant inferior or inferolateral dipyridamole thallium scintigraphy abnormalities are not associated with a lower risk of cardiac complications following vascular surgery than anterior abnormalities. Rather, any clearly abnormal dipyridamole thallium study is a marker for increased risk of perioperative events and may warrant further evaluation and treatment.

Aged↗
PubMedDate not supplied

Overview of lipoprotein metabolism: mechanisms involved and conveying this information to patients.

The major classes of lipoprotein particles are chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and high-density lipoproteins. Each of these particles has distinct characteristics, including a distinct apolipoprotein composition. The basic functions of these major apolipoproteins are briefly summarized for clinicians, and disorders of lipoprotein metabolism are discussed. For the effective management of lipid disorders, the therapy should be tailored to the specific defect. Compliance may be improved if the patient understands the nature of the particular lipid problem. To that end, we have developed an analogy in which the various classes of lipoprotein particles are equated to different trucking systems, and the liver is considered a warehouse for storage and distribution of fat. With use of this explanation, patients may understand the rationale for selection of various therapeutic strategies, and treatment of the hyper-lipoproteinemia is likely to be more successful.

Journal Article↗
PubMedDate not supplied

Interleukin-10 expression: is there a neglected contribution of CD8+ T cells in rheumatoid arthritis joints?

OBJECTIVE: To search for RA specific processes among T cell accumulation, T cell activation, or cytokine expression in CD4+ and CD8+ synovial fluid (SF) T cells. METHODS: Flow cytometry of CD4+, CD8+, CD45RA+, CD45RO+, CD69 double or triple stained peripheral blood (PB) and SF T cells. IL-2, IL-10, and IFN-gamma expression was determined in PMA + ionomycin stimulated T cells on the single cell level. Concentrations of secreted IL-2, IL-4, IL-10, and IFN-gamma were quantified in the sera and synovial fluids by enzyme linked immunosorbent assay (ELISA). RESULTS: A preferential recruitment of CD45RO+ memory T cells was found for CD4+ helper T cells, and in similar also for CD8+ suppressor T cells. An elevated CD69 expression was detected in memory, but also in CD45RA+ naive CD4+ and CD8+ SF T cells, whilst IL-2 expression was only demonstrable in a minor proportion of T cells populations. Preferential recruitment of memory T cells, but incomplete activation of naive and memory, CD4+ and CD8+ T cells were in similar found in RA and control patients. In RA but not in the control patients, a relevant proportion of CD4+ and CD8+ PB and SF T cells expressed IL-10 and IFN-gamma. High concentrations of IL-10, that were correlated with the amounts of secreted TNF-alpha, were only detected in RA joints. CONCLUSION: Memory and naive T cell state of CD4+ and CD8+ T cell accumulates in the joints, and early T cell activation occur in similar patterns in RA and control patients. High IL-10 SF concentrations in contrast, and elevated percentages of IFN-gamma and IL-10 expressing CD4+ and CD8+ T cells in the PB and SF were characteristic for RA. Here, CD8+ T cells may contribute to high IL-10 concentrations in RA joints.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Role of the endopeptidase 24.11 in the disposition and metabolism of endogenous atrial natriuretic factor in the rabbit.

The neutral endopeptidase 24.11 (NEP) has been shown to inactivate the atrial natriuretic factor (ANF) by opening the ring structure. To document the role of NEP in the metabolic fate of ANF in vivo, the effects of an infusion of thiorphan (25 micrograms/min/kg), a specific NEP inhibitor, on the kinetics and metabolism of endogenous ANF were studied in conscious rabbits. A bolus of [125I]ANF(99-126) was injected 50 min after the beginning of the infusion of thiorphan. Plasma samples containing the radioactive peptides were separated by reverse-phase HPLC. The parent compound could be separated from at least two other minor metabolites, corresponding to the elution position of [125I]ANF(99-105/106-126), the inactive ring-opened metabolite, and of [125I]ANF(103-126), an N-truncated analog. The generation of the N-truncated metabolite was increased by thiorphan. Thiorphan also induced an increase in plasma ANF (29%) that was closely associated with a 32% reduction in the systemic clearance of [125I]ANF(99-126), whereas no modification in the estimated secretion rate was detected. These results support a role for NEP in the regulation of endogenous ANF plasma levels. These results also suggest that specific inhibition of NEP may result in an increase in the apparent activity of alternative metabolic pathways.

Animals↗
PubMedDate not supplied

[The effect of the cerebrospinal fluid from rats subjected to picrotoxin-induced kindling on the motor activity and seizure susceptibility of recipient animals].

Experiments on rats have shown that repeated administration of primarily subthreshold dose of picrotoxin leads to the occurrence and progressive enhancement of seizure manifestations. During picrotoxin kindling the decrease of locomotor activity in interictal periods was recorded. Microinjection of cerebrospinal fluid (CSF) of kindled rats into lateral brain ventriculi of recipients resulted in decrease of locomotor activity and acute primarily generalized picrotoxin induced seizures. These effects of CSF were blocked by naloxone administration and were observed only if injecting CSF which was preliminarily treated with protease inhibitors. It is concluded that endogenous opioid substances accumulate in CNS during kindling and evoke a decrease in the locomotor activity. These substances act as anticonvulsant factors which control the development of epileptic activity.

Animals↗
PubMedDate not supplied

Angiotensin II receptor subtypes and their selective nonpeptide ligands.

Two types of angiotensin II (AII) receptor (AII-1 and AII-2) have been identified in rat adrenal cortex by means of two highly specific, but structurally dissimilar, nonpeptide AII receptor antagonists, DuP753 and EXP655, and by the discriminatory effect of dithiothreitol (DTT). Using radioligand-receptor binding techniques, DuP753 was found to be highly specific for AII-1 sites, displaying an inhibitory potency value of 1.2 x 10(-8) M. This type of AII receptor was particularly sensitive to inactivation by DTT. EXP655 possessed no affinity for the AII-1 sites, but was highly selective for the AII-2 sites exhibiting an inhibitory potency value of approx 10(-7). The AII-2 receptors were found resistant to DTT inactivation. A limited survey of the tissue distribution of these receptor subtypes indicates that AII-1 sites are exclusively found in vascular tissues, whereas AII-2 sites are highly enriched in adrenal medulla and brain.

Adrenal Cortex↗
PubMedDate not supplied

Liquid chromatographic determination of flavor enhancers and chloride in food.

A liquid chromatographic method is described for the simultaneous determination of flavor enhancers (glutamate, inosine-5'-monophosphate, and guanosine-5'-monophosphate) and chloride (salt) added to food. This rapid method exhibits excellent recoveries, and does not require derivatization or gradient elution by refractive index and UV detection in series.

Chlorides↗
PubMedDate not supplied

Significant enhancement of carbon dioxide removal by a new prototype IVOX.

The intravenacaval blood gas exchanger (IVOX) developed by Cardiopulmonics, Inc. has been tested in animals and in human clinical trials for partial support of gas exchange (25-30%) to allow reduction in mechanical ventilatory support and barotrauma during acute respiratory failure. After recognizing the limitations of the device and limited clinical utility of removing only 25-30% of CO2 production, the authors have made design changes in the IVOX (prototypes IIA and IIB), including increased fiber number, decreased fiber length, decreased fiber diameter, and increased crimping. Nine ewes underwent placement of the IVOX prototypes in an ovine model of severe smoke inhalation injury. A modification of the original insertion technique was used to implant the prototypes. CO2 removal was directly measured from the outlet gas. O2 exchange was calculated from IVOX on/off measurements. Neither IVOX IIA nor IIB significantly changed hemodynamics when a fluid bolus (15 ml/kg) was infused before insertion. There were no significant differences between prototypes regarding thrombosis, emboli, or incidence of bleeding complications. Both prototypes significantly improved CO2 removal (60-80%) compared with that reported for an older IVOX model. The improved gas transfer by these prototypes would serve to decrease mechanical ventilatory requirements and barotrauma in the treatment of severe respiratory failure.

Animals↗