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Biomedical subjects

P Nguyen

Publications and source records attributed to P Nguyen.

At least 145 records · Page 8Linked to original sources
PubMed1994

[Hemorheologic changes in preoperative hemodilution during total hip replacement. Randomized study comparing hydroxyethyl starch 200,000/0.62 (HES) and a dextran 60,000].

Hemodilution can be used to save blood transfusion during total hip replacement. We have carried out a randomized study to compare the hemorheological effects of two plasma substitutes: a hydroxyethylstarch 200,000/0.62 versus a dextran 60,000. Twenty-two patients were hemodiluted with 20 mk/kg of either substitute, just after the spinal anesthesia. Whereas the hematocrit have fallen by 30% in the two groups, significant differences are observed about hemorheological parameters. The plasma viscosity express a greater increase at hour 4 in the dextran group. The whole blood viscosities are more increased in the dextran group at hour 4 and 24. The erythrocyte aggregation is decreased in the HES group at hour 4 and 24, but is increased in the dextran group. The fibrinogen is more increased in the dextran group at day 7. In spite of similar hemodilutions, the two substitutes express different hemorheological effects with a favourable role of HES on erythrocyte aggregation and blood viscosities. This can improve the microcirculation and decrease the activation of the endothelial cells, reducing the inflammatory reaction.

Adult↗
PubMed1994

Binding of retinoid analogues to albumin and lipoproteins of human plasma.

The interactions of ten retinoid derivatives with human serum albumin (HSA) and lipoproteins have been investigated in vitro by an erythrocyte-partitioning technique that allows a quantitative estimation of the protein and erythrocyte binding. It was found that all these compounds were highly bound to HSA and lipoprotein. The binding to HSA was superior or similar to the binding to lipoprotein in the case of carboxylic acid derivatives. For the neutral derivatives, the binding to lipoproteins was generally higher than the binding to HSA. Retinoid binding to lipoproteins was strongly related to the computed octanol water partition coefficient (CLOGP).

Albumins↗
PubMed1994

Erythrocyte aggregation--determination of normal values. Influence of age, sex, hormonal state, oestroprogestative treatment, haematological parameters and cigarette smoking.

Erythrocyte aggregation is a physiological phenomenon and constitutes one of the most important factors accounting for the non-Newtonian properties of normal human blood. Pathological aspects have also been described and therapy aimed at reducing hyperaggregability has been proposed. The object of this study was to establish normal values of erythrocyte aggregation parameters as measured by laser light backscattering and to study the influence of various physiological factors. Normal values were determined from a reference population. Sex and age induce variations in erythrocyte aggregation which are neither fibrinogen nor haematocrit dependent and there is a general trend towards stronger aggregation in women, although neither hormonal state nor oestroprogestative treatment appear to influence the female aggregation parameters. In elderly people stronger aggregation is also observed but this effect is of lower magnitude. In vivo, the plasma fibrinogen level is the most important factor influencing erythrocyte aggregation, while variations in haematocrit play a lesser role and mean corpuscular volume, red cell distribution width and white blood cell and platelet counts have no effect. Finally, no difference is noted in cigarette smokers.

Adolescent↗
PubMed1994

Heparin-induced thrombocytopenia: a survey of tests employed and attitudes in haematology laboratories. Groupe d'Etude sur l'Hémostase et la Thrombose (GEHT) de la Société Française d'Hématologie.

A survey was carried out of the attitudes adopted in French laboratories with regard to the diagnosis of heparin-induced thrombocytopenia (HIT). The platelet aggregation assay is used in 100% of laboratories, aggregation being measured by light transmission in an aggregometer (3/4). Blood is drawn either in emergency (1/4) or after heparin discontinuation (1/4). The nature of the samples for testing is a fresh citrated plasma (100%) although frozen plasma is occasionally employed, while 40% of laboratories use less than 3 control platelet donors. Platelet response is verified in the presence of a non immune agonist (18%) or an immune challenge (known positive plasma or platelet activating monoclonal antibody) (13%). Heparin is of the same type as received by the patient and is tested at two or more concentrations of approximately 0.5 and 1.0 IU/ml, but rarely at high concentration (100 IU/ml). The platelet count is adjusted to 250-350 x 10(9)/l (18%), the ratio of patient plasma to PRP is 1:1 (59%), the time of observation is about 20 min (50%) and control platelets are tested with heparin to rule out any false positive results (9/10). Standardization is nevertheless required if the platelet aggregation assay is to be considered as a reference test.

Artifacts↗
PubMed1993

Variations of protein C in uremic hemodialysed patients.

Protein C has been measured by three different assays (antigenic, amidolytic and chronometric) in 27 end-stage renal insufficient patients before and after hemodialysis. Protein C levels have been compared with other coagulation inhibitors (antithrombin III, protein S) and fibrinolytic parameters. Baseline anticoagulant activity of protein C has been found impaired in eight cases whereas other inhibitors were normal. In four cases, both anticoagulant and antigenic levels were low. In one case, amidolytic method could also found a low activity. Hemodialysis leads to an increase of protein C activity and antigen level. Heparinemia after hemodialysis does not interfere with the chronometric measurement of protein C anticoagulant activity. Total protein level, hematocrit, protein S and antithrombin III are also elevated after hemodialysis. Baseline fibrinolytic parameters are normal and remain unchanged after hemodialysis. The clinical relevance of such modifications is discussed.

Adult↗
PubMed1993

Enantioselective detoxication of optical isomers of glycidyl ethers.

The detoxication of the enantiomers of glycidyl 4-nitrophenyl ether (GNPE), (-)-(R)- and (+)-(S)-GNPE, and glycidyl 1-naphthyl ether (GNE), (-)-(R)- and (+)-(S)-GNE, by rat liver glutathione transferase and epoxide hydrolase was studied. Enantioselectivity was observed with both enzymes favoring the (R)-isomers as determined by the formation of conjugate, diol, and remaining substrate measured by HPLC. Enantiomers of GNE were detoxified by cytosolic epoxide hydrolase but those of GNPE were not. Substantial nonenzymatically formed conjugates of enantiomers of GNPE were detected showing (S)-GNPE the more reactive of the pair.

Animals↗
PubMed1993

Human serum albumin conformational changes as induced by tenoxicam and modified by simultaneous diazepam binding.

The binding of tenoxicam to human serum albumin has been shown by affinity chromatography proton titration and equilibrium dialysis to be dependent on the neutral to basic conformational change of the protein. The influence of diazepam on the interaction was also investigated using the same techniques, suggesting that diazepam increases the association of tenoxicam to albumin. Affinity chromatography revealed that the reciprocal effect also occurs. Displacement studies indicated that diazepam causes a significant increase in the affinity of tenoxicam to its main binding site, albumin site I, which is different from the diazepam site (site II). Tenoxicam seemed to cause an allosteric change in the conformation of the protein during its own binding, as did warfarin. The mechanism of this effect was a pH-dependent conformational change of albumin induced by electrostatic forces within the protein. Diazepam induced a distant accommodation of the protein, an effect accompanied by an enhanced inhibition of the release of protons from albumin.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Growth and clinical course of children with Crohn's disease.

Growth impairment is a common complication of childhood Crohn's disease, but longitudinal data and follow up studies into adulthood are sparse. This study reviewed the records of 100 Tanner stages 1 and 2 children (66 males, 34 females) consecutively diagnosed with Crohn's disease at this hospital between January 1980 and June 1988. The influence of sex, anatomical location of disease, severity of symptoms, corticosteroids, and surgical intervention on growth were analysed by univariate and multivariate regression analysis. At diagnosis mean standard deviation score (SDS) for height was -1.11 (1.28) (males -1.14 (1.26), females -1.05 (1.33)). Twenty one children were below the third centile for height. During years one and two height velocity (cm/y) was 4.4 (2.3) and 5.1 (2.7), but 40% of children in year one and 33% of children in year two grew less than expected (< 4 cm). Forty nine children grew < 4 cm/y during two or more of the 4.9 (1.8) years of follow up. Severity of gastrointestinal symptoms was the major factor influencing linear growth velocity (p < 0.01 for years one and two). Despite the high prevalence of growth impairment, the subset of children who had reached maturity by the time of the study (n = 67) nevertheless maintained their height centile. The SDS for height at ultimate follow up was -0.82 (1.1). Compared with diagnosis, change in SDS was +0.35 (1.08). Growth increments were comparable for surgically treated patients v patients only treated medically and among patients stratified by location of disease. Females (n = 25) achieved greater catch up growth than males (n = 42). Ultimate SDS for height for females was -0.48 (0.91) v -1.02 (1.19) for males. Change in SDS for height was +0.66 (1.27) for females v +0.16 (0.90) for males (p=0.02). These data confirm the frequency of growth impairment in childhood Crohn's disease. After diagnosis, however, the prognosis for ultimate linear growth is good.

Adolescent↗
PubMed1993

Intraoperative versus interstitial radiotherapy: a comparison of morbidity in the head and neck.

Intraoperative radiation therapy (IORT) and interstitial radiotherapy (brachytherapy) are highly effective adjunctive treatments for head and neck cancer. The radiotolerance of the carotid artery, pharynx, and mandible to therapeutic doses of these modalities, however, has not been clearly established. To investigate the effects of IORT and interstitial iridium 192 (192Ir) on these structures in the canine, both sides of the neck of 12 mongrel dogs were operated on to expose 4-cm segments of the common carotid artery, pharynx, and mandible. One side of the neck was irradiated in each animal with the opposite side serving as the unirradiated control. The animals were divided into 3 groups of 4 dogs each. The first group received 40-Gy IORT and the second, 60-Gy IORT. In the third group of animals, afterloading catheters were implanted followed by placement of 60-Gy 192Ir. At 2 and 4 months after irradiation, 2 dogs in each treatment group were killed and histopathologic examination of the carotid artery, pharynx, and mandible was performed using hematoxylin-eosin staining. No statistically significant difference between treatment groups was found for carotid artery injury, but a trend for the proportion of fibrosis of the carotid on the irradiated side to increase with dose (P = .125) and time (P = .250) was noted. No apparent or statistically significant difference was found between treatment groups for pharyngeal injury. The greatest histologic changes noted following IORT and 192Ir brachytherapy were found in mandible specimens. The incidence of bone marrow suppression in irradiated mandible specimens versus controls approached statistical significance (P = .062). Osteoradionecrosis (ORN) was noted in the irradiated mandible specimens of two dogs, one of which received 60-Gy IORT and the other 60-Gy interstitial 192Ir. This manuscript reviews animal and clinical investigations relevant to the use of IORT and interstitial radiotherapy to the head and neck. Recommendations are made regarding further animal and clinical research as well as methods of treatment.

Animals↗
PubMed1993

Nimesulide binding to components within blood.

The binding of nimesulide within human serum to isolated proteins and to erythrocytes was studied by equilibrium dialysis. Within the range of therapeutic concentrations, nimesulide was 99% bound to serum involving a nonsaturated process (NKA = 91). This binding was almost identical to binding of nimesulide to serum albumin (NKA = 95). Physiological concentrations of free fatty acids did not affect binding of nimesulide to serum albumin. The retention of nimesulide by erythrocytes suspended in buffer was moderate (67%), although in whole blood no erythrocyte binding was observed because of the greater affinity of this drug for serum. Over the range of therapeutic concentrations (2.5 to 63 mumol/L), the free fraction of nimesulide in serum remains constant. Serum binding was decreased in samples obtained from patients with renal failure or hepatic cirrhosis associated with hypoalbuminaemia and hyperbilirubinaemia, respectively. At therapeutic concentrations, the binding of nimesulide was unaffected by warfarin, cefoperazone, furosemide (frusemide), glibenclamide, tamoxifen or digitoxin. However, valproic acid and fenofibrate (80 mumol/L) may displace nimesulide. 4-Hydroxy-nimesulide, the principal metabolite, significantly increased the free fraction of nimesulide. Although methotrexate had no effect on the free fraction of nimesulide, the free fraction of methotrexate was significantly increased in the presence of nimesulide. The present study also demonstrated 2 distinct nimesulide binding sites (site I and site II) on serum albumin (10 mumol/L) with different affinities: site II KA = 3.57 x 10(5) L/mol and site I KA = 1.24 x 10(5) L/mol. Interaction studies using markers that bind specifically to site I (warfarin and azapropazone) and site II (diazepam and ibuprofen) indicated that nimesulide binds to site II with higher affinity and to a lesser extent to site I.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Clinical pharmacology of oxicams: new insights into the mechanisms of their dose-dependent toxicity.

Six oxicams, sudoxicam, isoxicam, piroxicam, tenoxicam, meloxicam and lornoxicam, were compared in an attempt to understand why, despite close chemical structures, two of them were associated with an increased risk of toxicity in patients. Different factors have been revealed which may explain these differences. A weak association constant to human serum albumin (HSA), together with a high plasma concentration, favours a rapid increase in unbound concentration (Cu) when total plasma concentration rises (peak of absorption). Pathological states may enhance this increase when both HSA plasma concentration is decreased and free fatty acid concentrations are increased. However, the main cause of toxicity may be the existence in some subjects of HSA natural mutants whose ability to bind oxicams is markedly lower than normal.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Morphine place conditioning is differentially affected by CCKA and CCKB receptor antagonists.

In the present study we have examined the interaction between the selective cholecystokinin (CCK)A and CCKB receptor antagonists, devazepide and L365-260 on morphine conditioned place preference (CPP). Using an unbiased procedure, morphine (1.5 mg/kg) produced a reliable CPP which was observed irrespective of the conditioning compartment type. Pretreatment with devazepide (0.001-0.01 mg/kg s.c.) produced a dose related attenuation of this response. At higher doses (0.1-1 mg/kg) this antagonism became variable and dependent on the training compartment with blockade only observed when conditioning was to the white/rough textured environment. This profile has also been reported for the serotonin (5-HT)3 receptor antagonist ondansetron. The CCKB antagonist L365-260 (0.000001-0.01 mg/kg) failed to antagonize the morphine CPP, if anything a mild potentiation was observed. To study this further we examined the interaction between L365-260 (0.01 mg/kg) and a subthreshold dose of morphine (0.3 mg/kg). At these doses neither drug elicited CPP, however when co-administered a significant CPP was recorded. Finally, L365-260 at 1 mg/kg induced a mild but significant CPP when administered alone. These results suggest a differential role of CCK receptor subtypes on reward-related behaviour and complement previous studies suggesting bimodal effects of CCK systems on mesolimbic dopamine function.

Animals↗
PubMed1992

Effect of the 5-HT3 receptor antagonists, MDL72222 and ondansetron on morphine place conditioning.

The purpose of the present study was to reassess the original findings of Carboni et al. (1988) who suggested that 5-HT3 receptor antagonists may block morphine-induced place conditioning in rats. These workers used a biased protocol with treatments allocated to compartments based on initial preference. In the present study we have adopted an unbiased approach with treatments randomly assigned to conditioning compartment in a counter-balanced fashion. Thus treatments were equally paired between distinct environmental cues. Using this protocol, morphine produced a dose-related place preference (0.3-3 mg/kg SC). Thirty-minute pretreatment with the selective 5-HT3 antagonists, MDL72222 (1 mg/kg SC) and ondansetron (0.01 mg/kg SC) before morphine (1.5 mg/kg SC), significantly antagonized the place conditioning to this treatment. However, with higher doses of ondansetron (0.1-1 mg/kg SC), the antagonism of morphine-induced place preference became variable and dependent on the conditioning compartment. This was probably a reflection of the fact that ondansetron when administered alone also appeared to produce an environmentally dependent place conditioning at these doses. Therefore it is concluded that at certain doses, 5-HT3 receptor antagonists may antagonize morphine place conditioning in a manner consistent with a blockade of the appetitive effects of this drug. However, at higher doses, at least with ondansetron, this antagonism became non-specific and dependent on the training environment. It is suggested that other animal models of opioid reinforcement (e.g., self-administration) are now needed to validate the hypothesis that 5-HT3 receptor antagonists may modify opioid reward.

Animals↗
PubMed1992

The NMDA antagonist dizocilpine (MK801) attenuates motivational as well as somatic aspects of naloxone precipitated opioid withdrawal.

The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine has recently been reported to antagonize certain overt withdrawal signs in morphine dependent rats. The purpose of the present study was to reassess this response and examine the effect of this drug in a model presumably reflective of the motivational impact of withdrawal using the place conditioning technique. Rats were made opiate dependent by the subcutaneous implantation of a 75 mg morphine pellet. Three-4 days later withdrawal was precipitated by naloxone 0.5 mg/kg. Dizocilpine (0.1-0.5 mg/kg) attenuated many of the subsequent behaviours elicited by naloxone, notably diarrhoea, mouth movements, paw shakes and ptosis. In a separate group of morphine dependent rats, naloxone (0.05 mg/kg) precipitated withdrawal produced a clear place aversion. This place aversion was blocked by dizocilpine (0.02-0.1 mg/kg) pre-treatment prior to conditioning. Therefore dizocilpine may modify both motivational and somatic aspects of opioid withdrawal.

Animals↗
PubMed1992

SV40 small t deletion mutants preferentially transform mononuclear phagocytes and B lymphocytes in vivo.

Hamsters injected intracardiacally with wild-type SV40 developed diverse tumors, with no one type predominating. However, hamsters injected with small t deletion mutants of SV40 uniformly developed true histiocytic or B-cell lymphomas, both of which arise from rapidly dividing cell populations, with very few tumors of other types. Our results are consistent with in vitro studies which suggest a requirement for the small t function in SV40 transformation of nondividing cells.

Animals↗