[A little known segment of the cardiac wall: the muscular atrioventricular septum].
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Biomedical subjects
Publications and source records attributed to T L Nguyen.
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A method for the simultaneous quantitation of imipramine and its N-demethylated metabolite desipramine at the nanogram level in a single gas chromatograph peak is presented, utilizing gas chromatography-mass spectrometry with selected ion recording. The assay is specific and quantitation is achieved using [2H4]imipramine as the internal standard. The method involves the in situ methylation of desipramine with [2H2]formaldehyde and sodium borohydride to give [2H2]imipramine. Quantitation is then achieved by selected ion recording at m/z 280, 282 and 284, whence the ratio of the ion currents at 280/284 and at 282/284 gives the quantities of imipramine and desipramine respectively.
The urinary excretion of ORG NC 45 (Vecuronium) and of pancuronium was studied in unanesthetized rats and the biliary excretion was studied in anesthetized rats. Urine and bile were analyzed for unchanged drug by a new and specific mass spectrometric assay. Pancuronium was eliminated primarily in the urine (85% +/- 6% of the dose in 12 hours), but little ORG NC 45 appeared in the urine (3.5% +/- 1.1% in 12 hours). Biliary excretion accounted for 46% +/- 4% of the ORG NC 45 dose in 7 hours, but only 7.5% +/- 5.3% of an injected dose of pancuronium appeared in the bile. Thus, it appears that ORG NC 45 (a monoquaternary ammonium compound) has a higher biliary clearance than pancuronium (a bisquaternary ammonium compound). The different biodisposition of these two compounds may be due to the greater lipophilicity and concomitant enhanced permeability into the hepatocyte of ORG NC 45. We conclude that in the rat elimination of pancuronium is primarily via the kidney whereas elimination of ORG NC 45 is dependent on nonrenal mechanisms.
To determine the influence of renal failure on the pharmacokinetics and neuromuscular blockade of Org NC 45 (Norcuron), a new monoquaternary homologue of pancuronium, 13 patients under halothane and nitrous oxide anesthesia were studied. Org NC 45 was administered by 2-min infusion in doses of 0.28 mg kg-1 (normal renal function group, n = 4) and 0.14 mg kg-1 (renal failure group, n = 5). Four additional patients with normal renal function were given Org NC 45 0.14 mg kg-1 to determine the onset, duration and recovery rate of neuromuscular blockade. The serum concentration of Org NC 45 was determined by normal-phase high performance liquid chromatography (sensitivity 50 ng ml-1), and a two-compartment open pharmacokinetic model was fitted to resulting data. Estimates of distribution half-life (T 1/2 alpha), elimination half-life (T 1/2 beta), volume of distribution at steady state (Vss) and clearance of Org NC 45 did not differ significantly between patients with normal renal function and those with renal failure. The onset, duration and recovery rate times of the neuromuscular blockade by Org NC 45 0.14 mg kg-1 in patients with normal renal function and those with renal failure did not differ significantly.
The morpho-biochemical characteristics were studied on 115 wild strains of Cryptococcus albidus: 61 isolates of the variety albidus and 54 of the variety diffluens. The mucous aspect of the colony, the pigmentation, the development on liquid medium, the cells' form and the filamentation were the morphological characters observed. As for the physiology, were reported the results concerning: the fermentation, the assimilation of 24 carbohydrates and the potassium nitrate, the development according: the temperature, two rates of actidione (cycloheximide) and four rates of tetrazolium. Were discussed: the atypicity and the intra-specific variations, the differenciation of the varieties and the taxonomic value of the two entities.
Cannabidiol (CBD), 600 mg/day orally for 5 to 12 days, inhibited hexobarbital metabolism in ten subjects. Hexobarbital oral clearance was 36% lower and apparent volume of distribution was 35% smaller, with no change in half-life during CBD. In four subjects who received intravenous and oral hexobarbital, systemic clearance was 36% lower while bioavailability was 10% greater during CBD. Hexobarbital increased fatigue and tremor, impaired eye-tracking performance, and altered the electroencephalogram. Hexobarbital effects were not affected by CBD. Inhibition of metabolism of other drugs should be considered when large amounts of CBD are taken or when CBD is used for therapy.
The maximal temperature for growth was investigated on 208 Cryptococcus, 2 type cultures and 206 wild strains, belonging to 11 species or varieties. According to the results, which spread from 25 degrees to 42 degrees, the Cryptococcus were separated in three groups. The differentiation of C. neoformans from other Cryptococcus developing at 37 degrees, and particularly from two species with near bio-chemical characteristics, was discussed.
Studies on the metabolism of nicotine by rabbit liver microsomal fractions in the presence of 0.01 M sodium cyanide have led to the characterization of two isomeric cyanonicotine compounds. The locations of the cyano groups were established by GC--EIMS analyses of the deuterium-labeled products obtained from the specifically deuterium-labeled substrates (S)-nicotine-5',5'-d2, (R,S)-nicotine-2',5',5'-d3, and (R,S)-nicotine-N-methyl-d3. One cyano adduct was shown to be 5'-cyanonicotine, a product previously isolated from similar microsomal preparations. The second cyano adduct was shown to be N-cyanomethyl)nornicotine; this structure assignment was confirmed by synthesis. Formation of N-cyanomethyl)nornicotine appears to occur, at least in part, without prior nitrogen--carbon bond cleavage, implicating the in situ generation of the N-methyleniminium species during the course of metabolic oxidative N-demethylation of nicotine.
Osseous cells in culture synthesize and excrete glycosaminoglycans, collagen and alkaline phosphatases, revealed by the classical histochemical reactions. Observation of the living cells iwth the polarizing microscope, after a five day-culture, reveals the presence of micro-crystals of mineral salts only at the level of cells and cellular groupings.
A technique of osseous cells culture has been perfected through discontinuous enzymatic digestion of young Mice prietal bones and using a chemically defined medium buffered by means of hepes. The cultural characteristics observed seem to correspond to those of osteogenic cells.
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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.
The impact of dengue haemorrhagic fever (DHF) on liver function was studied by measuring serum transaminase levels on 45 patients with DHF confirmed by virus isolation and serodiagnosis in 1995. Abnormal levels of AST and ALT were observed in 97.7 and 37.3% of the patients, respectively. The fact that the level of AST was higher than that of ALT and that the elevation of transaminases was mild to moderate in most cases (< 5-fold greater than the normal upper limit for AST and ALT) showed that liver involvement was also mild to moderate in most cases of DHF. The results of transaminases did not differ significantly between cases with and without hepatitis B or hepatitis C virus infection, nor between primary and secondary cases of infection, but a significantly higher elevation of AST and ALT was observed in DHF patients with gastrointestinal haemorrhage. Two patients with dengue encephalopathy (in 1992) and one patient with dengue encephalopathy who died of massive gastrointestinal haemorrhage (in 1995) had unusually high transaminase levels as a sign of acute liver failure. It is concluded that DHF may cause mild to moderate liver dysfunction in most cases; only some patients may suffer from acute liver failure leading to encephalopathy and death.
The liver is one of the organs in which hypoxia helps to regulate gene expression under normal physiological conditions and in diseases such as cirrhosis and cancer. We postulated that the expression/activity of some of the 'liver-enriched' transcription factors, which control liver-specific genes, was sensitive to hypoxia. We tested hepatocyte nuclear factor-1 (HNF-1), HNF-3 and HNF-4, which play key roles in differentiation, development and hepatic gene expression, using HepG2 human hepatoma cells cultured under hypoxic conditions. Severe hypoxia/anoxia downregulated HNF-4 DNA-binding activity while DNA-binding activity of HNF-1 and HNF-3 remained unaffected. These hypoxic conditions also strongly and specifically decreased cell contents of HNF-4 protein, indicating that the decrease in HNF-4 DNA-binding activity was due to the lower amount of protein and not to decreased DNA-binding affinity. Northern analysis indicated that the expression of the hnf-4 gene was also downregulated in HepG2 cells cultured under hypoxic conditions. These results provide evidence that hypoxic stress triggers a cascade of events that inhibits the transactivation potential of HNF-4 in HepG2 cells. This step may be crucial in modulating the expression of a subset of liver genes that are targets for this nuclear receptor. This relationship provides a new route for the investigation of the effects of hypoxia on the liver cell.
The study was performed in the area of distribution of tropical malaria resistant to 4-aminoquinolines (Vietnam) on 30 patients receiving lariam (mefloquine). The results were compared to the standard therapy with quinine and fansidar. They indicate a high efficacy of and a good tolerance to the drug tested. The use of lariam leads to a more rapid (as compared to the standard treatment) elimination of parasitemia and complete eradication of the disease relapses. The findings make it possible to recommend lariam for the prevention and treatment of tropical malaria.