Search PubMed⌕ Search

Biomedical subjects

A T Nguyen

Publications and source records attributed to A T Nguyen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Nitric oxide does not reverse pulmonary hypertension associated with end-stage liver disease: a preliminary report.

Pulmonary hypertension is a well known, though uncommon complication of end-stage liver disease (ESLD). Patients with severe pulmonary hypertension and ESLD undergoing orthotopic liver transplantation (OLT) may develop right ventricular failure and death. This study investigates the reversibility of pulmonary hypertension by the inhalation of nitric oxide in patients under evaluation for OLT. Ten patients with ESLD who were discovered to have moderate to severe pulmonary hypertension were administered nitric oxide via face mask in concentrations ranging from 0 to 80 ppm. Inhaled nitric oxide is a potent pulmonary vasodilator without apparent systemic effects. Nitric oxide had no demonstrable effect on mean pulmonary artery pressure (PAP) (37 vs. 37 mm Hg), transpulmonary gradient (TPG) (26 vs. 26 mm Hg), or pulmonary vascular resistance (PVR) (295 vs. 288 dynes x sec x cm (-5)). Two patients were discovered to have an elevated pulmonary artery occlusion pressure (PAOP) on baseline readings. The cause of pulmonary hypertension in these two patients was secondary to volume overload as a result of hepato-renal syndrome rather than primary pulmonary arteriolar pathology and was responsive to diuresis or dialysis but not to nitric oxide therapy. In conclusion nitric oxide does not reverse pulmonary hypertension associated with ESLD.

Administration, Inhalation↗
PubMed1997

Severe pulmonary hypertension in liver transplant candidates.

Advanced liver disease with portal hypertension may be associated with pulmonary hypertension. A review of 1,205 consecutive liver transplant patients was made to assess the incidence and severity of pulmonary hypertension in patients with end-stage liver disease. Postoperative data were reviewed to determine if outcome was influenced and, in patients with severe pulmonary hypertension, whether pulmonary hypertension was reversed after transplantation. The hemodynamic data of 5 patients who were found to have severe pulmonary hypertension before transplantation and did not receive transplants were also reviewed. The incidence of pulmonary hypertension in the patients who received transplants was 8.5% (n = 102; mean pulmonary artery pressure, > 25 mmHg). The incidence of mild pulmonary hypertension was 6.72% (n = 81; systolic pulmonary artery pressure, 30 to 44 mmHg); that of moderate pulmonary hypertension was 1.16% (n = 14; systolic pulmonary artery pressure, 45 to 59 mmHg); and that of severe pulmonary hypertension was 0.58% (n = 7; systolic pulmonary artery pressure, > 60 mmHg). Mild and moderate pulmonary hypertension did not influence the outcome of the procedure. Severe pulmonary hypertension was associated with mortality rates of 42% at 9 months posttransplantation and 71% at 36 months posttransplantation. Only 2 of 7 patients with severe pulmonary hypertension have survived liver transplantation with a good quality of life. The remaining 5 patients continued to deteriorate with progressive right heart failure with no evidence of amelioration of the pulmonary hypertension. This experience supports the view that in most patients who have severe pulmonary hypertension associated with advanced liver disease, it is caused by fixed pathological changes in the pulmonary vasculature, is not reversible with liver transplantation, and is associated with a very high perioperative mortality rate.

Adult↗
PubMed1997

Duration of rocuronium-induced neuromuscular block during liver transplantation: a predictor of primary allograft function.

The prolongation of vecuronium-induced neuromuscular block has been reported as a predictor of hepatic allograft dysfunction. This study investigates the duration of action of rocuronium, which also relies on hepatic clearance, to examine whether it also is prolonged with allograft dysfunction. Fifty-seven patients undergoing orthotopic liver transplant were given rocuronium (0.6 mg/kg) prior to allograft placement and the recovery of contraction of the orbicularis oculi muscle to a 2-Hz train-of-four stimulus was recorded. Fifteen minutes after reperfusion of the allograft, rocuronium (0.6 mg/kg) was administered and the time to recovery of muscle contraction to a train-of-four stimulus (train-of-four time) was again recorded. The patients were divided into two groups according to posttransplant liver function. Group I consisted of 50 patients with immediate normal liver function. Group II contained 7 patients with primary dysfunctional livers. Primary dysfunction was determined by peak serum aspartate aminotransferase and alanine aminotransferase levels > 2000 U/L, and prothrombin time > 16 s. The train-of-four time in Group II was prolonged compared with Group I (P < 0.05). Immediate graft function testing using the recovery time from rocuronium of > 150 min has a positive predictive value of 100% and a negative predictive value of 96%. The sensitivity and specificity is 71% and 100%, respectively. Receiver operating characteristic analysis supports this conclusion.

Adolescent↗
PubMed1997

Continuous small-dose tranexamic acid reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation.

Tranexamic acid (TA) is a synthetic drug that inhibits fibrinolysis. It has been administered to decrease the use of blood products during cardiac surgery and orthotopic liver transplantation when infused in larger doses. A small-dose infusion of aprotinin causes a reduction in fibrinolysis and blood product requirement during orthotopic liver transplantation without apparent risk of intravascular thrombosis. This prospective study was designed to investigate whether a small-dose infusion of TA would be equally effective in reducing fibrinolysis and blood product transfusions during orthotopic liver transplantation. A double-blind, controlled study was undertaken to compare the efficacy of a small-dose TA infusion with that of a placebo. Thirty-two consecutive patients were randomized either to the TA group (n = 16), which received an intravenous infusion of 2 mg x kg(-1) x h(-1), or to the control group (n = 16), which received an identical volume of normal saline. Coagulation values were measured, a field rating was made by the surgeon, and a thromboelastogram was produced at four predetermined intervals throughout the case-before TA infusion was started, after portal vein ligation, 10 min after reperfusion, and at the end of surgery. Intraoperative transfusion requirements were recorded during the procedure and for the first 24 h postoperatively. A record was kept of any intraoperative epsilon-aminocaproic acid administered for uncontrolled fibrinolysis. The thromboelastogram clot lysis index was significant for lysis in the control group during both the anhepatic and the neohepatic phases (P < 0.01 and P < 0.05, respectively) when compared with the TA group. Fibrin degradation products were significantly increased (>20 microg/mL) in the control group at reperfusion (P < 0.03) and at the end of surgery (P < 0.01). D-dimers were also significantly increased (>1 mg/L) in the control group at the end of surgery (P < 0.04). Nine of the 16 control patients versus 3 of the 16 TA patients required epsilon-aminocaproic acid rescue for fibrinolysis. There were no other significant differences between groups. Transfusion requirements during surgery and for the first 24 h postoperatively did not differ significantly between the two groups. We conclude that the use of small-dose TA reduces fibrinolysis but not transfusion requirements during orthotopic liver transplantation.

Aminocaproic Acid↗
PubMed1997

[Benefits of early nephrological management of chronic renal failure].

OBJECTIVES: We evaluated whether early nephrological referral of patients with chronic renal failure (CRF) resulted in improved condition of patients at initiation of maintenance dialysis and in better outcome on dialysis. PATIENTS AND METHODS: We prospectively recorded clinical status, laboratory parameters, length of hospital stay and outcome of 900 CRF patients who started maintenance dialysis at Necker hospital between January 1989 and December 1996. We compared patients who benefited regular nephrological follow-up, and patients who were referred in emergency conditions at the ultimate stage of CRF. RESULTS: Among the 900 patients, 731 (81.2%) had regular nephrological follow-up, including 632 (70.2%, group IA) with optimal preparation to dialysis and 99 (11%, group IB) whose clinical course was complicated due to heavy comorbidity, whereas 169 (18.8%, group II) had no previous nephrological management. Over the 8-year observation period, the proportion of the latter group did not decrease. Late referred patients had higher blood pressure level, more frequent fluid overload, higher serum levels of urea, creatinine, uric acid and phosphate, and lower levels of bicarbonate, calcium, albumin and creatinine clearance that did well-prepared patients. Mean (+/- SD) hospital stay was 29.7 +/- 15.8 days in the former compared to only 4.8 +/- 3.3 days (p < 0.001) in the latter. Early deaths within 3 months of dialysis initiation were more frequent (7.1 vs 1.6% p < 0.05) and less patients subsequently were able to be treated out-center (20.1 vs 40.7%, p < 0.05) in group II than in group IA. The overcost induced by late referral may be estimated at 0.25 million French francs per patient. CONCLUSION: An unjustified late nephrological referral of CRF patients still is observed in nearly 20% of cases. Such late referral is detrimental to both patients in terms of altered quality of life and long hospital stay, and to the collectivity due to heavy overcost. Closer cooperation between family physicians and nephrologists is needed to provide optimal management and allow timely preparation to maintenance dialysis of CRF patients.

Female↗
PubMed1996

Disturbed myeloperoxidase-dependent activity of neutrophils in cystic fibrosis homozygotes and heterozygotes, and its correction by amiloride.

The present study addresses the question of a possible linkage between the cystic fibrosis (CF) genetic autosomal recessive disorder and disturbance in neutrophil function. Neutrophil-dominated chronic airway inflammation is present at an early age in children with CF, even in the absence of detectable infection. As evidenced by extracellular superoxide anion release (measured by lucigenin luminescence) or intracellular hydrogen peroxide production (measured by 2',7'-dichlorofluorescein (DCF) fluorescence), no significant difference in the nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activity of isolated neutrophils was observed in noninfected CF children (homozygotes), their mothers or fathers (CF heterozygotes), and controls. In contrast, both myeloperoxidase (MPO)-dependent oxygenation activity (measured by luminol luminescence) and chloramine release were increased significantly in both CF homozygotes and heterozygotes as compared with controls. In the presence of either amiloride (a sodium channel inhibitor and sodium/proton antiport blocker) or EIPA (5-ethyl-N-isopropyl-amiloride, a specific inhibitor of the antiport), or choline buffer, intracellular MPO activity was decreased significantly in controls and in the CF homozygotes and heterozygotes, thus bringing intracellular MPO-dependent activity in CF subjects back to the level of controls. Extracellular release of MPO, measured by an ELISA to provide an activity-independent assessment of the enzyme, was increased only in CF homozygotes, and was decreased by amiloride and choline buffer, but not by EIPA. We conclude that a modification of intracellular pH and/or ionic concentrations may be related to the altered MPO enzymatic activity observed in CF neutrophils.

Adolescent↗
PubMed1996

Expression of functional HIV-1 integrase in the yeast Saccharomyces cerevisiae leads to the emergence of a lethal phenotype: potential use for inhibitor screening.

The integrase of the human immunodeficiency virus type 1 (HIV-1) has been expressed in yeast in order to investigate its potential lethal effect mediated by DNA damage. To this end, we have constructed an expression plasmid containing the retroviral integrase gene under the control of the inducible promotor ADH2/GAPDH which is regulated by the glucose concentration of the medium. Haploid yeast strain W303-1A did not appear to be clearly sensitive to HIV-1 integrase expression. However, disruption of the RAD 52 gene, which is involved in the repair of double-strand DNA breaks, strongly increased the deleterious effects of the retroviral enzyme in this yeast strain. The diploid strain constructed with W303-1A and an isogenic strain of the opposite mating type also showed a strong sensitivity to the HIV-1 integrase. Under yeast culture conditions allowing moderate integrase synthesis, the deleterious effect was totally abolished by missense integrase mutations, which are known to abolish HIV-1 integrase activities in vitro. We conclude that the lethal phenotype due to HIV-1 integrase expression in yeast may be closely related to the HIV-1 integration reaction in infected human cells, and that yeast may be a useful tool to study the HIV-1 integration process and to screen drugs capable of inhibiting HIV-1 integration in vivo.

Antiviral Agents↗
PubMed1996

Glutathione antioxidant system as a marker of oxidative stress in chronic renal failure.

A profound imbalance between oxidants and antioxidants has been suggested in uremic patients on maintenance hemodialysis. However, the respective influence of uremia and dialysis procedure has not been evaluated. Circulating levels of copper-zinc superoxide dismutase (CuZn SOD), glutathione peroxidase (GSH-Px), and reductase (GSSG-Rd), total GSH and GSSG were determined in a large cohort of 233 uremic patients including 185 undialyzed patients with mild to severe chronic renal failure, and 48 patients treated by peritoneal dialysis or hemodialysis. Compared to controls, erythrocyte GSH-Px and GSSG-Rd activities were significantly increased at the mild stage of chronic uremia (p < .001), whereas erythrocyte CuZn SOD activity was unchanged, total level of GSH and plasma GSH-Px activity were significantly decreased, and GSSG level and GSSG-Rd activity were unchanged. Positive Spearman rank correlations were observed between creatinine clearance and plasma levels of GSH-Px (r = .65, p < .001), selenium (r = .47, p < .001), and GSH (r = .41, p < .001). Alterations in antioxidant systems gradually increased with the degree of renal failure, further rose in patients on peritoneal dialysis and culminated in hemodialysis patients in whom an almost complete abolishment of GSH-Px activity was observed. In conclusion, such disturbances in antioxidant systems that occur from the early stage of chronic uremia and are exacerbated by dialysis provide additional evidence for a resulting oxidative stress that could contribute to the development of accelerated atherosclerosis and other long-term complications in uremic patients.

Antioxidants↗
PubMed1996

Role of endogenous cardiac glycosides in the spontaneously hypertensive rat--antagonism by active immunization.

The effects of simultaneous active immunization against two cardiac glycoside drugs, digoxin and proscillaridin, have been examined in young spontaneously hypertensive and Wistar-Kyoto rats. Control animals were immunized with protein carrier only. Animals were studied from 5 weeks to 13 weeks of age. Effectiveness of immunization to produce antibody responses was assessed at the end of the study by estimating the titer of antibodies in plasma against both of the antigens. Robust antibody responses were obtained. Immunization had no effect on the normal growth of these animals. Further, immunization against cardiac glycosides did not change blood pressure in either strain of animals. Blood pressure in the SHR increased as anticipated as the weanling animals grew to maturity. These studies indicate that active immunization against cardiac glycosides does not alter blood pressure in the SHR in spite of strong evidence for increased levels of endogenous cardiac glycosides in this strain.

Animals↗
PubMed1996

Advanced oxidation protein products as a novel marker of oxidative stress in uremia.

Evidence suggests an imbalance between antioxidant and oxidant-generating systems resulting in oxidative stress in uremic patients. As plasma proteins are critical targets for oxidants, we developed a novel spectrophotometric assay which allows to detect advanced oxidation protein products (AOPP) in uremic plasma. By size-exclusion chromatography AOPP are retrieved in two distinct peaks at 600 and below 80 kDa in uremic plasma, while no such peaks are found in control plasma. Further biochemical characterization revealed that AOPP are carried by oxidized plasma proteins, especially albumin and do not have oxidant properties. AOPP increased in a dose-dependent manner following in vitro exposure of plasma or purified human serum albumin (HSA) to hypochlorous acid. Advanced glycation end products of human serum albumin (AGE-HSA) also increased AOPP levels. In vivo, plasma level of AOPP was the highest in patients on hemodialysis, followed by those on peritoneal dialysis and by undialyzed patients with advanced chronic renal failure. AOPP levels correlated with plasma concentrations of dityrosine and AGE-pentosidine, as indices of oxidant-mediated protein damage, but not with thiobarbituric reactive substances as lipid peroxidation markers. A close correlation was also found between AOPP and neopterin levels, suggesting that AOPP could be part in the monocyte-mediated inflammatory disorders associated with uremia. In conclusion, we propose the measurement of AOPP as a reliable marker to estimate the degree of oxidant-mediated protein damage in uremic patients and to predict the potential efficacy of therapeutic strategies aimed at reducing such an oxidative stress.

Biomarkers↗
PubMed1996

The advanced glycation endproduct pentosidine and monocyte activation in uremia.

RATIONALE: Advanced glycation endproducts (AGEs) contribute to the pathogenesis of vascular complications in diabetes, aging and end-stage renal disease (ESRD). Immune abnormalities in patients with chronic renal failure and those treated by dialysis contribute to high rates of morbidity and mortality. We therefore sought a relationship between a circulating marker of immune dysfunction and plasma levels of the AGE pentosidine. METHOD: We studied non-diabetic patients with mild to advanced renal failure (n = 60), and with ESRD treated by hemodialysis (HD) (n = 44) and peritoneal dialysis (PD) (n = 19). The plasma protein content of the well characterized AGE, pentosidine was measured using HPLC. In the same samples the monocyte activation product neopterin was measured by RIA. RESULTS: Plasma levels of pentosidine and neopterin increased in parallel with the progression of renal failure. Pentosidine and neopterin were highly correlated in all patients even after adjustment for Ccr. This correlation was also present in patients with ESRD. CONCLUSION: These data suggest that the AGE pentosidine is associated with monocyte activation in renal failure, an interaction which may contribute to accelerated rates of complication and death by as yet unknown mechanisms.

Arginine↗
PubMed1996

Presumed ocular tuberculosis in an AIDS patient.

BACKGROUND: Prior to the advent of anti-tuberculosis medications, ocular manifestations of tuberculosis, including choroidal tubercles, were common. METHODS: A 46-year-old Hispanic male with a history of AIDS, tuberculosis and treated neurosyphilis presented for examination complaining of decreased vision in the left eye. Ophthalmoscopy revealed a large, elevated, juxtapapillary lesion consistent with a choroidal tubercle or an intraocular lymphoma. RESULTS: During follow-up, the lesion responded well to systemic anti-tuberculosis therapy. CONCLUSIONS: With the recent increase in incidence of tuberculosis in both th general population and AIDS patients, ocular manifestations of tuberculosis once thought to be rare may be increasing. Ocular tuberculosis should be considered in the differential diagnosis of patients presenting with intraocular masses, especially in individuals at high risk for exposure.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[Dysregulation of the immune system in chronic uremic and hemodialysed patients].

Concomitant immune deficiency and activation of immuno-competent cells, together with a disequilibrium between inflammation-inducing cytokines and their specific natural inhibitors is the basis of our current understanding of immune system dysregulation in patients with chronic uraemia. These anomalies may even be accentuated by dialysis. Clinically, bacterial infections, viral hepatitis and amyloidosis all play important roles. Humoral factors include abnormal immunoglobulin response to specific antibodies and complement activation. The response of T lymphocytes, long sought as the origin of the immunodeficiency associated with chronic uraemia, is also significantly decreased in these patients. The decreased antibody responses to specific stimuli may be related to B cell dysfunction. Monocyte and polymorphonuclear cell reactions are also perturbed. A deficiency in natural killer cells is observed although the mechanisms involved and the consequences are still debated. The factors determining the anomalies leading to immune system dysregulation in chronic uraemia and dialysis and their relationship with the reduction in active nephron mass as well as their metabolic and/or endocrine consequences remain to be fully described. A better understanding of the mechanisms involved should lead to new strategies for immuno-intervention in patients with chronic renal failure and help in optimizing haemodialysis.

Chronic Disease↗
PubMed1995

Balance between IL-1 beta, TNF-alpha, and their specific inhibitors in chronic renal failure and maintenance dialysis. Relationships with activation markers of T cells, B cells, and monocytes.

Patients with end-stage renal disease present an immunodeficiency that paradoxically coexists with activation of most immunocompetent cells, and the roles of chronic uremia and maintenance dialysis are poorly understood. We determined circulating levels of IL-1 beta and IL-1Ra, TNF-alpha and its soluble receptors (TNF-sR55 and TNF-sR75), and activation markers of T cells (soluble CD25), B cells (soluble CD23), and monocytes (neopterin) in a large cohort of undialyzed patients at various stages of chronic renal failure and in dialyzed patients on maintenance hemodialysis or chronic peritoneal dialysis. The progression of uremia was associated with a gradual increase in soluble CD25, CD23, and especially neopterin levels. Although IL-1 beta could not be detected, IL-1Ra levels were significantly increased from the earliest stage of renal failure. Plasma levels of TNF-alpha, TNF-sR55, and TNF-sR75 progressed with the severity of renal failure and correlated with soluble CD25, CD23, and neopterin levels, whereas IL-1Ra levels correlated exclusively with TNF-sR55 levels. Compared with undialyzed patients, levels of IL-1 beta were higher in patients on maintenance hemodialysis, whereas those of IL-1Ra were lower and decreased further at the end of dialysis sessions. In contrast, both TNF-sR55 and TNF-sR75 levels were significantly higher than in undialyzed patients and increased further at the end of dialysis sessions in the absence of an increase of TNF-alpha. Such an imbalance between cytokines and their inhibitors may play a pivotal role in the multifaceted process of immune dysfunction.

B-Lymphocytes↗
PubMed1995

Neutrophil-derived long-lived oxidants in cystic fibrosis sputum.

We evaluated long-lived oxidant potential in the sputum of patients with cystic fibrosis (CF) by quantitating the methionine-inhibitable, long-lived oxidant fraction of sputum, referred to as the chloramines. Taurine, the preferred amino acid substrate for chloramine formation, and myeloperoxidase (MPO), the chlorinated oxidant-generating enzyme, were also quantitated. As compared with the sputum of asthmatic subjects, the sputum of CF patients contained high concentrations of chloramines along with high levels of taurine and active MPO. A negative correlation between chloramine and taurine was found in the sputum of CF patients. No correlation was found between the density of Pseudomonas aeruginosa and the level of chloramines, taurine, or MPO. In contrast, respiratory parameters (%FEV or %FVC) and a nutritional index correlated positively with chloramine levels, whereas negative correlations were observed with taurine and MPO. In addition, the effect of antibiotic therapy, which significantly increased chloramine and decreased taurine levels, supported a beneficial effect of chloramines on overall clinical status. Our findings support a dual role of long-lived oxidants at the site of airway inflammation in CF, one component of which is their ability to mediate oxidative stress and the other a beneficial effect that may be partly explained by their inhibitory effect on antiprotease defense systems.

Adolescent↗
PubMed1995

Circumscribed choroidal hemangioma.

BACKGROUND: Circumscribed or solitary choroidal hemangioma is a relatively rare, benign vascular tumor. Because its appearance may mimic more serious intraocular lesions, eye care practitioners should be familiar with differential diagnosis and treatment options. METHODS: A patient presented with an asymptomatic, elevated, red-orange lesion above the macula in the right eye and a history of longstanding unexplained visual acuity loss in the eye. Intraocular lesions such as amelanotic melanoma, metastatic tumor, choroidal osteoma, disciform scar, serous detachment, and central serous chorioretinopathy can appear similar to circumscribed choroidal hemangioma (CCH) on ophthalmoscopy, but may be differentially diagnosed with fluorescein angiography, ultrasonography, and periodic observation. RESULTS: CCH requires various therapeutic options. Until the patient becomes symptomatic from visual loss secondary to serous macular detachment or subretinal neovascular membrane formation, no treatment is necessary. Laser photocoagulation is the preferred therapeutic intervention, and most patients will require a minimum of two sessions. A small percentage of individuals will progress to complete retinal detachment with profound visual loss regardless of therapy. Most CCHs remain stable in size and do not undergo malignant transformation. CONCLUSIONS: CCHs may be overlooked because of their initial subtle clinical appearance with no associated cutaneous or systemic anomaly. Even though CCH is a benign tumor, it may mimic more serious intraocular lesions and require a combination of ancillary tests for proper diagnosis. Depending on visual symptoms or potential threat to vision, management options include periodic observation, laser photocoagulation, cryotherapy, microwave therapy, and possible enucleation. CCH has little or no growth potential, but visual prognosis remains guarded due to significant secondary retinal changes that can occur over the tumor's surface. CCH must be considered in the differential diagnosis of an elevated intraocular lesion.

Aged↗
PubMed1994

In vitro and in vivo activities of reduced-size antagonists of luteinizing hormone-releasing hormone.

A novel series of octapeptide LHRH antagonists was designed on the basis of the structure of the (2-9) fragment of a LHRH agonist. By adopting a systematic SAR study, we were able to improve first the in vitro activity and then the in vivo LH suppression, raising them up to the range of the decapeptide antagonists NalGlu (51) and A-75998 (50), resulting in A-76154 (49). The octapeptide antagonist A-76154 is the most potent reduced-size LHRH antagonist reported. It suppresses LH in the castrated rat by over 80% for a period of 4 h following sc bolus administration of 30 micrograms/kg.

Amino Acid Sequence↗