Biomedical subjects
Publications and source records attributed to M H Nguyen.
Sterilization by tubal occlusive methods has a small but definite incidence of failure which is not well recognized among general surgeons. As a result of the failure to appreciate the possibility of ectopic pregnancy after tubal ligation, right-sided abdominal pain in this patient population is commonly misdiagnosed as appendicitis. One such case is presented, and the literature is reviewed and discussed.
The (-) enantiomers of 2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC] and 2',3'-dideoxy-3'-thiacytidine [(-)-BCH-189] were recently shown to inhibit selectively human immunodeficiency viruses (HIV) and hepatitis B virus in vitro. In the current study, the potential for HIV type 1 (HIV-1) resistance to these compounds was evaluated by serial passage of the virus in human peripheral blood mononuclear cells and MT-2 cells in the presence of increasing drug concentrations. Highly drug-resistant HIV-1 variants dominated the replicating virus population after two or more cycles of infection. The resistant variants were cross-resistant to (-)-FTC, (-)-BCH-189, and their (+) congeners but remained susceptible to 2',3'-dideoxycytidine, 3'-azido-3'-deoxythymidine, 3'-fluoro-3'-deoxythymidine, 2',3'-dideoxyinosine, phosphonoformate, the TIBO compound R82150, and the bis(heteroaryl)piperazine derivative U-87201E. Reverse transcriptase derived from drug-resistant viral particles was 15- to 50-fold less susceptible to the 5'-triphosphates of FTC and BCH-189 compared with enzyme from parental drug-susceptible virus. DNA sequence analysis of the reverse transcriptase gene amplified from resistant viruses consistently identified mutations at codon 184 from Met (ATG) to Val (GTG or GTA) or Ile (ATA). Sequence analysis of amplified reverse transcriptase from a patient who had received (-)-BCH-189 therapy for 4 months demonstrated a mixture of the Met-184-to-Val (GTG) mutation and the parental genotype, indicating that the Met-184 mutation can occur in vivo.
Anionic surfactants, especially alkylbenzene sulfonates, are discharged into marine areas in great quantities. Because of their poor biodegradability, linear alkylbenzene sulfonates accumulate in seawater and sediments. Bacterial communities that can degrade surfactants were selected from coastal seawater contaminated by urban sewage. All the isolated strains consisted of gram-negative, strictly aerobic rods or helical bacteria. Some of these, though isolated from coastal seawater, did not need sodium for growth and appeared to be related to the genera Alcaligenes and Pseudomonas. Complete surfactant biodegradation was achieved by three important steps: terminal oxidation of the alkyl chain, desulfonation, and aromatic-ring cleavage. Only a few strains were able to carry out the first two steps. The aromatic ring was then cleaved by other strains that possess very specific enzymatic activities. Finally, a number of strains grew on short acids that were end-of-metabolism products of the others.
Legionella is a common cause of community- and hospital-acquired pneumonia. New information on the pathogenesis of infection and the host immune response is reviewed. Specialized laboratory tests, especially culture, are necessary for diagnosis since the clinical presentation is nonspecific. New antimicrobial agents and innovative approaches to disinfection of water distribution systems are presented.
The synthesis of products of the 5-lipoxygenase pathway by synovial fluid (SF) and peripheral blood neutrophils of 12 patients with rheumatoid arthritis was compared in 3 experimental conditions using high performance liquid chromatographic analysis. Major differences were observed when blood and SF neutrophils were incubated with ionophore A23187, the formation of all 5-lipoxygenase products being lower (p less than 0.0005) in the SF neutrophils. Addition of exogenous arachidonic acid to the A23187 stimulated cells partially overcame the difference in 5-lipoxygenase product synthesis between the 2 neutrophil populations. In contrast, upon incubation with arachidonic acid alone, SF neutrophils produced significantly larger amounts of 5-lipoxygenase products. The increased reactivity of the SF neutrophil 5-lipoxygenase to arachidonic acid and the decreased 5-lipoxygenase product synthesis upon A23187 stimulation may be the consequence of the previous activation of the cells and 5-lipoxygenase product synthesis in situ.
Human granulocyte-macrophage colony-stimulating factor (GM-CSF) is an in vitro and in vivo stimulator of human bone marrow myelomonocytic precursor cells and mature granulocyte and macrophage effector cells. We have compared the effect of GM-CSF on the synthesis of 5-lipoxygenase products induced by the chemotactic peptide fMet-Leu-Phe and the calcium ionophore A23187 in human neutrophils. Although GM-CSF alone did not stimulate detectable synthesis of products of the 5-lipoxygenase pathway, pre-incubation of neutrophils with 200 pM GM-CSF for 1 hour at 23 degrees C enhanced synthesis of leukotriene B4, its all-trans isomers and omega-oxidation products, and 5-hydroxyeicosatetraenoic acid in response to both the calcium ionophore A23187 (1.5 microM), and the chemotactic peptide fMet-Leu-Phe (0.1 microM). This priming effect of GM-CSF was maximal after a 60 min incubation at 23 degrees C, or after a 30 min preincubation at 37 degrees C. The effect of GM-CSF was maximal using a concentration of 1 nM. Enhancement of the leukotriene synthesis stimulated by A23187 was only observed when the cells were stimulated by the ionophore for periods of 3 minutes or less. In contrast, the enhancing effect of GM-CSF was still apparent when cells were exposed to fMet-Leu-Phe for as long as 15 minutes. Furthermore, the enhancing effect of GM-CSF was ablated when neutrophils were stimulated with A23187 and exogenous arachidonic acid. However, co-addition of exogenous arachidonic acid with fMet-Leu-Phe did not entirely mask the effect of GM-CSF. Possible mechanisms of action of GM-CSF are discussed.
The carboxyl methylation of secretory proteins in vivo was investigated in bovine adrenal medullary cells in culture. Chromogranin A, the major intragranular secretory protein in adrenal medullary cells, and other secretory proteins were found to be carboxyl-methylated within secretory vesicles. The in vivo labeling pattern using [methyl-3H]methionine and the in vitro labeling pattern using S-adenosyl-[methyl-14C]methionine of intravesicular secretory proteins were similar. The detection of methylated chromogranin A in mature secretory vesicles required 3-6 h, a time consistent with the synthesis and storage of secretory proteins in this tissue. Carboxyl-methylated chromogranin A was secreted from medullary cells by exocytosis via activation of nicotinic cholinergic receptor and recovered still under the methylated form in the incubation medium. Since protein-carboxyl-methylase is cytosolic, these results suggest that methylation of secretory proteins is a cotranslational phenomenon.
Bacterial communities that can degrade surfactants have been selected from coastal seawaters contaminated by urban sewages. Only the linear fraction of commercial anionic surfactants was quickly degraded, and a residual fraction representing 10% of the initial concentration always remained. The highest concentrations of surfactant tolerated by these communities depend on the nature of the co-substrate and on the degree of adaptation of the selected bacteria.
This study was designed to examine the influence of physical training on the norepinephrine turnover rate in heart, pancreas, liver, and gastrocnemius muscles of normal and diabetic male rats at rest. Diabetes was induced with the IV injection of streptozotocin (45 mg/kg) and physical training was done on a treadmill according to a ten-week program. Norepinephrine turnover rate of tissues was estimated by following over time the decay in the specific activity of norepinephrine after a single IV bolus of tritiated norepinephrine (30 microCi/kg). Plasma glucose, insulin, and glucagon levels were also measured at the time of death. Although training caused a reduction in the plasma glucose values of diabetic rats, no changes in norepinephrine turnover rate were observed after the conditioning program. On the other hand, diabetes was associated with a significant 30% to 40% decrease in the pancreatic norepinephrine turnover rate. It is concluded that the beneficial effects of physical training on diabetes mellitus cannot be explained by adaptive changes in the sympathetic nervous system activity and that further work will be necessary to elucidate the mechanism whereby streptozotocin diabetes diminishes the pancreatic norepinephrine turnover.
This study was designed to evaluate the possibility that the enhanced insulin sensitivity of physically trained normal and diabetic rats is due to adaptive changes in the adrenergic system. Mild diabetes mellitus was induced in male Wistar rats with streptozocin (STZ, 45 mg/kg i.v.) and a 10-wk conditioning program was conducted by having the animals run on a treadmill. Rats were cannulated 16 h after the last period of exercise and blood sampling was obtained 48 h later for basal plasma glucose, insulin, epinephrine, and norepinephrine determination. Catecholamine measurements were also made in adrenals, atria, and ventricles from sedentary control, trained control, sedentary diabetic, and trained diabetic rats. The previously reported beneficial effect of physical training on diabetes mellitus was reproduced. While diabetes mellitus did not modify the catecholamine levels, the training program provoked an increase in plasma epinephrine concentrations, with a concomitant significant rise in adrenal epinephrine content. In heart tissue, the epinephrine values also tended to be increased by training although statistical significance was not reached. These data suggest that basal secretion of epinephrine is somewhat increased in trained rats. Whether this may trigger adaptive changes that could be involved in the beneficial effect of physical training on experimental diabetes mellitus remains to be elucidated.
Muscarinic receptor activation on the AtT-20 clonal line of mouse pituitary corticotrophs, inhibits forskolin-stimulated cyclic AMP formation and adrenocorticotropin secretion. In this study, the effect of prolonged receptor stimulation with the muscarinic agonist oxotremorine was found to reduce, in a time-dependent manner, the ability of oxotremorine to inhibit the AtT-20 cell response to forskolin. Pretreatment with oxotremorine also reduced the density of muscarinic receptors without affecting the affinity of these sites for [3H]quinuclidinyl benzilate. In addition to desensitizing the muscarinic receptor, oxotremorine pretreatment also enhanced the ability of forskolin to stimulate cyclic AMP formation and adrenocorticotropin secretion. The apparent sensitizing effect on cyclic AMP synthesis, extended to other muscarinic agents as well as other secretory agonists, was dependent on the oxotremorine concentration used during pretreatment and required at least 2 hr of pretreatment. Enhancement of forskolin-stimulated cyclic AMP accumulation by oxotremorine pretreatment was blocked by cycloheximide and reversed by the muscarinic antagonist, (-)-scopolamine, or by a 5-hr recovery period after pretreatment. The data suggest that prolonged muscarinic receptor activation (rather than simple occupancy) leads to an enhancement of adenylate cyclase activity in AtT-20 cells; whether this effect is coupled to the progressive loss of the inhibitory function of the muscarinic receptor and the receptor down-regulation is unknown.
A diminished sympathetic activity has been related to training bradycardia seen at rest and during exercise. In order to evaluate if changes in heart adrenergic receptors can be one of the mechanisms by which the sympathetic responsiveness could be decreased by physical training, the number and affinity of beta-adrenergic receptors were determined in heart ventricular tissue of rats submitted to a 10-week running programme. Binding studies were done at different concentrations of (-)[3H] dihydroalprenolol (DHA) (0.5 to 14.4 nmol X litre-1) with ventricular membrane preparations from control and trained rats. Direct linear plot analysis revealed that physical training reduced the total number (1933 +/- 192 vs 2922 +/- 211 fmol X ventricles-1; P less than 0.01) density of beta-adrenergic receptors expressed either as fmol X mg-1 of membrane protein (34 +/- 3 vs 43 +/- 3; P less than 0.05) or as fmol X g-1 ventricle (1740 +/- 170 vs 2308 +/- 155; P less than 0.05). There was no significant change in the dissociation constant (3.11 +/- 0.14 vs 4.08 +/- 0.51 nmol X litre-1; P greater than 0.05). Basal plasma noradrenaline levels were not affected by training (116 +/- 18 vs 101 +/- 14 pg X cm-3; P greater than 0.10); however the adrenaline values were significantly higher in trained rats (91 +/- 16 vs 47 +/- 7 pg X cm-3; P less than 0.05). These data indicate that physical training induces changes at the level of beta-adrenergic receptors and this may partly explain the bradycardia seen in trained subjects and animals.
The effects of acetaldehyde (1 mM) and two known sulfhydryl reagents, diamide (0.25 mM) and cystamine (0.5 mM), on the perfused guinea pig heart were compared and were found to be markedly similar. All compounds increased heart rate and coronary flow. Dichloroisoproterenol blocked the increase in heart rate but not the increase in coronary flow. It is concluded that acetaldehyde may produce its effects by reaction with cellular thiols.
The action of a number of compounds able to react with thiols was tested on guinea-pig hearts perfused at constant pressure. The SH reagents used were NaNO2, oxidized glutathione, cystamine, diamide, 1,5-difluoro-2,4-dinitrobenzene, nitroglycerol, sodium nitroferricyanide and HgCl2. 6,6'-Dithiodinicotinic acid, an SH reagent that does not penetrate the cell, produced no effect. All the other SH reagents produced an increase in coronary flow. All except oxidized glutathione and nitroglycerol increased the heart rate. The increase in heart rate and oxygen consumption could be completely blocked by dichloroisoproterenol; the increase in coronary flow was not affected. Difluorodinitrobenzene, diamide, cystamine and NaNO2 significantly decreased the acid-soluble thiol content of the heart. For these compounds, there was a significant correlation between the decrease in coronary flow and the decrease in thiols. We conclude that in the isolated heart, most SH reagents, if used at the appropriate concentration, will increase the heart rate, probably by relaasing catecholamines. They will also decrease the coronary resistance, probably by a direct effect on the coronary vessels.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A bacterial community degrading branched alkylphenol ethoxylate (APE) was selected from coastal sea water intermittently polluted by urban sewage. This community degraded more than 99% of a standard surfactant, TRITON X 100, but I.R. analysis of the remaining compound showed the accumulation of APE2 (alkylphenol with a two units length ethoxylated chain) which seemed very recalcitrant to further biodegradation. Twenty-five strains were isolated from this community, essentially Gram negative and were related to Pseudomonas, Oceanospirillum or Deleya genera. Among these strains, only four were able to degrade APE9-10 (TRITON X 100). They were related to the Pseudomonas genus and were of marine origin. Pure cultures performed with these strains on TRITON X 100 gave APE5 and APE4 as end products. These products were further degraded to APE2 by two other strains unable to degrade the initial surfactant.
OBJECTIVES: To evaluate the morbidity and mortality of Candida fungemia and to assess the efficacy of low- vs high-dose amphotericin B and fluconazole vs amphotericin B in patients with candidemia. METHODS: Multicenter, prospective, observational study of 427 consecutive patients with candidemia. RESULTS: The mortality rate for patients with candidemia was 34%. The mortality rate for patients with catheter-related candidemia in whom the catheters were retained was significantly higher than that of patients in whom the catheters were removed (41% vs 21%, P < .001). We found no overall difference in mortality in patients treated with low-dose (total amphotericin B dose of < or = 500 mg) (13%) vs high-dose amphotericin B (total amphotericin B dose of > 500 mg) (15%), but the group treated with a low dose had fewer side effects (40%) than those treated with a high dose (55%) (P = .03). Fluconazole was as efficacious as amphotericin B in the therapy of candidemia, even when stratified by risk factors for mortality. Fewer side effects were seen with fluconazole (12%) compared with amphotericin B (44%) (P < .001). CONCLUSIONS: In selected patients with candidemia, low-dose amphotericin B was as efficacious as high-dose amphotericin B. Based on other studies and ours, fluconazole seems to be an alternative therapeutic option to amphotericin B in selected patients.