Papers by Thao Nguyen-khoa
The Journal of Immunology
ABSTRACT
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Revue des Maladies Respiratoires
Cystic fibrosis is a genetic recessive disorder caused by mutations in the gene that encodes the ... more Cystic fibrosis is a genetic recessive disorder caused by mutations in the gene that encodes the CFTR protein. The diagnosis of cystic fibrosis is usually established in early childhood but it is now being made in an increasing number of adults. Many of them present with mild or atypical cystic fibrosis clinical features, mostly lung disease. In addition, some adults with congenital bilateral absence of vas deferens or idiopathic chronic pancreatitis may be assigned a diagnosis of cystic fibrosis. The diagnosis of cystic fibrosis in adults should be based on the presence of one or more characteristic clinical features, a history of cystic fibrosis in a sibling, plus evidence of defective CFTR function as documented by elevated sweat chloride concentrations or abnormal ion transport across the nasal epithelium, or identification of mutations on both CFTR genes.
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Néphrologie
An abnormally high mortality from atherosclerotic cardiovascular (CV) accidents has long been rep... more An abnormally high mortality from atherosclerotic cardiovascular (CV) accidents has long been reported in patients on maintenance hemodialysis (HD). However, incidence of such complications had not been so far evaluated in chronic renal failure (CRF) patients not yet on dialysis. In a cohort study bearing on 232 predialysis CRF patients, followed as out-patients at Necker hospital, incidence of first myocardial infarction (MI) was three times higher than in the French general population in every age group and in both genders, with a mean (+/- SEM) age at onset of MI of 62.9 +/- 1.2 years. In a retrospective cooperative study involving 748 patients treated in 9 hemodialysis centers in the Ile-de-France area, incidence of first MI episodes did not differ before and after start of HD therapy and was similar to that observed in the cohort study. Mean age of patients at first MI, before and after start of HD, was respectively 62.4 +/- 1.6 and 63.7 +/- 1.5 years, a not significant difference. In conclusion, two epidemiologic studies confirm the existence of accelerated atherosclerosis in CRF patients, the incidence of MI being 3 times higher in uremic patients than in the general population in every age group and in both genders. The fact that incidence of first MI episodes and age at onset was similar in predialysis and in dialyzed patients suggests that the uremic state per se is a main determinant of such accelerated atherosclerosis. It results that therapeutic measures aimed at preventing development of atherosclerosis should be initiated from the early stage of CRF, long before start of renal replacement therapy.
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Asaio Journal, 1996
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Advances in nephrology from the Necker Hospital
UK PubMed Central (UKPMC) is an archive of life sciences journal literature.
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Annales de biologie clinique
Sweat test measuring the chloride ion (Cl(-)) concentration in sweat is a tool for the cystic fib... more Sweat test measuring the chloride ion (Cl(-)) concentration in sweat is a tool for the cystic fibrosis (CF) diagnosis. We evaluated analytical criteria of different available methods and compared them into five hospitals and throught a national quality control program. Sweat tests were performed by stimulation using pilocarpine iontophoresis, sweat collection and measurement of sweat Cl(-) (mmol/L) by titration (colorimetric or coulometric end-point) or by in situ direct potentiometry using a chloride-selective electrode. Indirect determination by sweat conductivity measurement was expressed in mmol/L sodium chloride (NaCl) equivalents (Eq). Linearity range was demonstrated for all measurement procedures in the range 10 to 120 mmol/L. Intra-laboratory coefficients of variation (CVs) were <5% for values between 10 and 100 mmol/L. Inter-laboratory CVs were <3% only for conductivity measurement whatever the range. The comparison of results obtained for a same sweat sample, simu...
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Journal of Cardiovascular Pharmacology, 1998
In 10 healthy normotensive volunteers on a normal sodium diet, we evaluated the renal effects of ... more In 10 healthy normotensive volunteers on a normal sodium diet, we evaluated the renal effects of a single oral dose of 50 mg of irbesartan (SR 47436, BMS 186295), an angiotensin II AT1-receptor antagonist, in baseline conditions and during an exogenous angiotensin II infusion (2.5 ng/kg/min). We used a double-blind, placebo-controlled, crossover design. Hormones, blood pressure, renal hemodynamics, and urinary electrolytes were measured during each phase. To examine further the determinants of glomerular filtration at the microcirculation level, fractional clearance of neutral dextran was performed, and sieving curves were applied on a hydrodynamic model of ultrafiltration. Irbesartan administration was followed by an increase in active renin and plasma angiotensin II concentrations and renal plasma flow without change of systemic blood pressure, glomerular filtration rate, or plasma aldosterone concentration. Irbesartan did not affect either sieving curves or glomerular ultrafiltration determinants. Angiotensin II infusion at 2.5 ng/kg/min elicited a slight pressor response accompanied by a decrease in glomerular filtration rate and renal plasma flow and an enhancement of fractional dextran clearance over the radius range explored (3.4-5.4 nm). The transcapillary glomerular pressure gradient deltaP and the ultrafiltration coefficient kf were computed to increase by 9% and to decrease by 23%, respectively, without change in intrinsic membrane properties. Pretreatment with irbesartan prevented all these effects of angiotensin II.
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Hepatology, 2006
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Critical Care Medicine, 2007
To estimate the capacity of plasma from septic shock patients to induce in vitro reactive oxygen ... more To estimate the capacity of plasma from septic shock patients to induce in vitro reactive oxygen species (ROS) production by endothelial cells and to analyze whether ROS production is related to the severity of the septic shock. Prospective, observational study. Medical intensive care unit in a university hospital. Twenty-one patients with septic shock. The in vitro capacity of plasma from septic shock patients to induce ROS production by naive human umbilical vein endothelial cells (HUVEC) was quantified by using a fluorescent probe (2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;,7&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-dichlorodihydrofluorescein diacetate). Blood samples were collected on day 1, day 3, and day 5 from 21 consecutive septic shock adult patients and from ten healthy volunteers. Patients mean age was 58 yrs old, mean Sequential Organ Failure Assessment (SOFA) score at admission was 12, mean severity illness assessed by Simplified Acute Physiology Score (SAPS) II was 53, and the mortality rate was 47%. In addition to assessment of in vitro ROS generation by HUVEC, oxidative stress in blood was evaluated by measuring lipid peroxidation products and enzymatic and nonenzymatic antioxidants. Septic shock was associated with oxidative stress and an imbalance in antioxidant status. As compared with controls, plasma-induced ROS production by naive HUVEC was significantly higher in septic shock. Moreover ROS production was significantly correlated with SAPS II (p = .028) and SOFA values (p = .0012) and was higher in nonsurvivors than in survivors. In contrast, no correlation was found between the severity of the septic shock and any of the levels of lipid peroxidation products or enzymatic and nonenzymatic antioxidants. Plasma from septic shock patients induces ROS formation by naive HUVEC, and the extent of ROS formation correlates with mortality and with criteria of the severity of septic shock as SOFA score and SAPS II.
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Nephrology Dialysis Transplantation
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ASAIO Journal, 1996
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Néphrologie
Cardiovascular (CV) disease in uremic patients is a major concern to the nephrologist because it ... more Cardiovascular (CV) disease in uremic patients is a major concern to the nephrologist because it represents the main cause of morbidity and mortality in chronic renal failure patients, both predialysis and while on dialysis therapy. CV mortality is 3 to 20 times higher in dialysis patients than in the general population at similar age. Of note, a high prevalence of CV comorbidity is already present at start of maintenance dialysis, and is predictive of subsequent mortality on dialysis. CV disease progresses over years prior to the onset of ESRD, because risk factors develop from the early stage of chronic renal insufficiency. However, CV disease may be prevented or attenuated in patients who benefit from early, regular care of CV risk factors. Mechanisms of uremic cardiopathy, the major cause of mortality in uremic patients, are multifactorial and their effects are cumulative. Risk factors for left ventricular hypertrophy are hypertension, anemia, fluid overload and arteriosclosis, all of which are amendable by therapy. Risk factors for accelerated atherosclerosis, responsible for ischemic cardiopathy and myocardial infarction, are both common factors (e.g., hypertension, tobacco smoking and diabetes) and factors more specific for the uremic state (e.g., dyslipidemia, hyperhomocysteinemia and oxidative stress), all of which also are amendable by proper therapy. As a result, mixed hypertensive and ischemic cardiomyopathy develops, ultimately leading to cardiac failure, together with accidents resulting from valvular and arterial calcifications (favored by calcium-phosphate disorders), and from occlusion of coronary, cerebral and peripheral arteries. Cardioprotective therapy thus has become a cornerstone in the management of chronic renal failure patients, in conjunction with renoprotective therapy. Cardioprotective strategy involves optimal treatment of hypertension, anemia, fluid overload, dyslipidemia, hyperhomocysteinemia and calcium-phosphate disorders, and smoking cessation. To achieve a maximal efficacy, such treatment has to be initiated as early as possible in the course of renal failure. Because of its complexity, the integrated combined nephrotective and cardioprotective therapy requires early and sustained guidance by a nephrologist throughout the whole predialysis period.
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Annales de biologie clinique
Incidence of cardiovascular events is higher in hemodialysis (HD) patients than in general popula... more Incidence of cardiovascular events is higher in hemodialysis (HD) patients than in general population. Oxidative stress represents a major specific risk factor of accelerated atheroma particularly in association with inflammation and malnutrition. The aim of our study is to evaluate a simple test of lipid peroxidation measurement using the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Free Oxygen Radical Monitor&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; (FORM) (Callegari, Italy). The results obtained in HD patients were compared to standard oxidative stress markers, such as thiobarbituric acid reacting substances, carbonyls and vitamin E in plasma, and glutathione, oxidized to reduced form ratio, in erythrocytes. In conclusion, the FORM system presents no sufficient sensibility and specificity to determine oxidative stress in HD patients.
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Journal of nephrology
New reliable oxidative stress markers are present in chronic renal failure (CRF) patients, indica... more New reliable oxidative stress markers are present in chronic renal failure (CRF) patients, indicating that CRF is a pro-oxidant state. However, the pathogenesis of oxidative stress in CRF patients remains poorly defined. Moreover, the limited data available provide no clear-cut evidence in favor of the clinical benefit of antioxidant manoeuvres aimed at reducing cardiovascular disease in CRF patients or in the general population as well. Therefore, no practical recommendations can be given at this stage, and further studies are clearly needed.
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La Presse Médicale
To determine the degree of anaemia corresponding to the decreasing levels of renal function in pa... more To determine the degree of anaemia corresponding to the decreasing levels of renal function in patients with chronic renal failure (CRF) and not yet on dialysis, and to assess the indications for treatment with recombinant erythropoeitin (epoetin). We studied the relationship between haemoglobin (Hb) concentration and creatinine clearance (Ccr) in 403 consecutive patients with CRF regularly monitored in nephrology consultations between January 1 and June 30, 1999, and who received appropriate iron and vitamin supplementation. These patients were then followed-up until June 30, 2000 or until maintenance dialysis was initiated. There was a significant and close correlation between the degree of anaemia and renal dysfunction. An Hb value&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;11 g/dl (corresponding to the present threshold for the indication of epoetin) was observed in 62% of patients with creatinine levels&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;400 micromol/l and in 58% when Ccr was&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;20 ml/mn/1.73 m2. Whatever the level of CRF, the degree of anaemia was higher in the women than in the men. Among the 123 patients who had to start maintenance dialysis during the observation period, 85 (69%) were treated with epoetin before dialysis was started. In patients with CRF, clinically symptomatic anaemia is more frequent than imagined, and early treatment is required. Regular monitoring of Hb and iron levels is mandatory in order to allow patients to benefit from timely initiation of epoetin and thus prevent the development of disabling asthenia and other deleterious consequences of anaemia.
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Advances in nephrology from the Necker Hospital
1. Adv Nephrol Necker Hosp. 2000;30:177-99. Atherosclerotic complications in chronic renal failur... more 1. Adv Nephrol Necker Hosp. 2000;30:177-99. Atherosclerotic complications in chronic renal failure: epidemiology and predictive factors. Jungers P, Nguyen Khoa T, Joly D, Choukroun G, Witko-Sarsat V, Massy ZA. University René-Descartes, Paris, France. ...
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Néphrologie
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