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Biomedical subjects

L Bussières

Publications and source records attributed to L Bussières.

At least 19 recordsLinked to original sources

[First trimester Down syndrome screening program using nuchal translucency and maternal serum markers: the Echo PAPP-A.78 study].

Successive development of different methods to screen down syndrome (DS) have had unexpected effects, leading to an inflation in the number of karyotypes ordered and the number of induced abortions. In our district (Yvelines, France), DS screening leads to perform 16% karyotypes rate. Rapid progress in biology and ultrasonography has enabled us to correct this overprescription by conducting an early screening program using a combination of ultrasound graphic and new biochemical markers (Pregnancy-associated plasma protein A and the free fraction of ss-hCG) which allow an overall evaluation of risk. This method has high sensitivity (85%) and leads to a false positive rate karyotypes in about 5% of pregnancies. The purpose of the study conducted between January 1, 2001 and December 31, 2002 in the Yvelines was to confirm the validity of this method and determine its reproducibility in routine practice. Five partners contributed to the study: the Regional delegation for clinical research of the Paris-public assistance hospitals (AP-HP), the district health insurance fund (CPAM 78), the Yvelines maternity network which includes all ten maternity wards in the district, and the Echo 78 association which includes all ultrasoundgraphists working in the district who accepted to participate as investigators, as well as five biology laboratories where DS screening was performed.

Adult↗

Recovery after relief of fetal urinary obstruction: morphological, functional and molecular aspects.

The effects of obstruction [urinary tract obstruction (UTO)] and relief on renal development were examined in an experimental model in the fetal lamb. Bladder outlet obstruction was performed at 60 days of gestation; relief was performed by vesicoamniotic shunting at 90 days of gestation. Studies were carried out in obstructed (OF60; n = 11), shunted (SF; n = 5), and control fetuses (CF; n = 11) at 120 days of gestation. Fetal UTO produced either hydronephrosis (64%) or dysplasia (36%); dysplasia was always associated with a reduction in the number of glomeruli [950 +/- 99 (dysplasia) vs. 1,852 +/- 249 (CF) glomeruli/section]. Obstructed fetuses had lower creatinine clearance [0.76 +/- 0.41 (OF60) vs. 0.96 +/- 0.21 (CF) ml x min(-1) x kg(-1)], higher sodium fractional excretion [17.2 +/- 20.3 (OF60) vs. 2.4 +/- 3.7% (CF)], and higher urinary concentration [80 +/- 30 (OF60) vs. 43 +/- 22 (CF) micromol/l] than controls. In SF, the number of glomeruli was increased at 120 days of gestation (1,643 +/- 106 glomeruli/section) compared with nondiverted fetuses (1,379 +/- 502 glomeruli/section), and the temporal pattern of PAX2, disrupted after obstruction, was restored. In conclusion, early fetal UTO leads to either renal hydronephrosis with normal glomerular development or dysplasia with a decreased number of glomeruli; in utero urine diversion performed before the end of nephrogenesis may allow a reversal of the glomerulogenesis arrest observed.

Animals↗

Growth, puberty and hypothalamic-pituitary function in children with suprasellar arachnoid cyst.

UNLABELLED: A suprasellar arachnoid cyst may cause disorders of growth, puberty and hypothalamic-pituitary function, due to the proximity of the cyst to the hypothalamic-pituitary area. A total of 30 patients (17 boys) with cyst diagnosed at 4.3 +/- 1 years were routinely evaluated at 5.4 +/- 1 years; 24 of them had one or multiple cyst derivations. Some 23 cases had an abnormal height, weight or puberty: short (< -2SD, 5 cases) or tall ( > 2SD, 10 cases) stature, overweight (body mass index, BMI, > 2SD, 6 cases), central precocious puberty (10 cases) and/or no progression of pubertal development (3 cases). The growth hormone (GH) peaks after pharmacological stimulation test were low (< 10 MICROg/L) in 16 patients, confirmed by a second evaluation in 8/11 of them. The plasma free thyroxine was low in five patients, prolactin was high in two and the cortisol and concomitant plasma and urinary osmolalities were normal. BMI was correlated negatively with the GH peaks (r = -0.37, P < 0.01) and positively with the plasma leptin concentrations (r = 0.55, P < 0.01). The plasma fasting insulin concentrations were also correlated negatively with the GH peaks (r = -0.55, P < 0.02) and positively with the plasma insulin-like growth factor I concentrations (r = 0.64, P < 0.002). The adult height (12 cases) was at 4SD in 1 and < -2SD in 4 patients, two of whom had precocious puberty untreated with gonadotropin releasing hormone (GnRH) analogue, and two had untreated GH deficiency. The adult height of those treated was normal. One girl had primary amenorrhoea and two boys had low plasma testosterone, despite a normal gonadotropin response to a GnRH test. CONCLUSION: Suprasellar arachnoid cysts may cause deficiencies of growth hormone and thyrotropin, stimulation of the hypothalamic-pituitary-gonadal axis, tall stature and/or overweight. These last two disorders may be due to hyperinsulinism, itself due to suprasellar arachnoid cyst.

Adolescent↗

The use of insulin-like growth factor 1 reference values for the diagnosis of growth hormone deficiency in prepubertal children.

OBJECTIVE: This study was done to determine whether the use of reference values obtained in children with idiopathic short stature (ISS) improved the clinical value of serum insulin-like growth factor I (IGF-1) as a tool for diagnosing GH deficiency (GHD) in prepubertal children. PATIENTS AND METHODS: Serum IGF-1 was measured with a new IRMA kit (IGFI-RIA CT, Cis Bio, Gif sur Yvette, France) in 168 prepubertal normal children and in prepubertal children with ISS (n = 68), organic GHD due to a craniopharyngioma (oGHD, n = 15) and permanent idiopathic GHD (iGHD, n = 28). RESULTS: IGF-1 was lower (P < 0.001) in iGHD than in either ISS or oGHD and was below the fifth percentile of the normal range in 29/68 ISS (43%), 8/15 oGHD (53%) and 28/28 (100%) iGHD patients. Three oGHD (20%) and two iGHD (7%) patients had a serum IGF-1 below the fifth percentile of the normal group but above the fifth percentile of the ISS group. Thus, a serum IGF-1 below the fifth percentile of the normal group distinguished between normal children and iGHD with 100% sensitivity, between normal and oGHD with 53% sensitivity and between normal and all GHD (idiopathic + organic) with 84% sensitivity; the overall specificity was only 57%. Conversely, a serum IGF-1 below the fifth percentile of the ISS population distinguished between ISS and iGHD with 93% sensitivity, between ISS and oGHD with 33% sensitivity and between ISS and all GHD with 72% sensitivity; the overall specificity was then 95%. CONCLUSIONS: A serum IGF-1 within the normal range virtually excludes idiopathic GHD but does not rule out organic GHD, whereas an IGF-1 below the ISS range is strongly in favour of GHD, after exclusion of poor nutritional status and/or liver disease. An IGF-1 below the normal range but in the idiopathic short stature range gives no definitive conclusion even when it is associated with a low GH peak. Thus, whereas reference values obtained in normal children must be used to interpret serum IGF-1 in short prepubertal children, reference data obtained in idiopathic short stature children should also be taken into account.

Child↗

Hormonal factors influencing weight and growth pattern in craniopharyngioma.

Patients operated on for craniopharyngioma frequently suffer from hyperphagia and are obese, but their statural growth is normal despite growth hormone (GH) deficiency. We have evaluated the hormonal factors influencing changes in weight and growth in 17 children before and 1, 3-6, 12, and/or 24 months after surgical resection of a craniopharyngioma performed at 7.7 +/- (SE) 1 years of age. Of these, 15 patients had a GH deficiency before surgery, and all had complete pituitary deficiency after it. The plasma fasting insulin concentrations before surgery were positively correlated with body mass index (BMI, kg/m(2); p < 0.05), plasma insulin-like growth factors (IGFI, p = 0.03, and IGFII, p = 0.04), and leptin (p = 0.03). They increased significantly 1 month after surgery and continued to increase thereafter, whereas leptin increased significantly only 3-6 months after surgery, paralleling changes in BMI. The plasma fasting insulin concentrations before surgery were also positively correlated with the weight changes (12.3 +/- 2.3 kg, p < 0.01) during the 12 months after surgery, but not with changes in BMI SDS (3.1 +/- 0.5, p = 0.07). Both expressions of weight change were correlated with the concomitant growth rates (4.8 +/- 0.7 cm, p < 0.01). IGFI was above the 10th percentile for children with idiopathic short stature in 10 of 15 patients with craniopharyngioma-induced GH deficiency and IGF-binding protein 3 in 14 of 15 patients. Craniopharyngioma itself modified the control of insulin secretion, and surgery increased the insulin secretion which continued in the same way in a given patient after surgery. The increased insulin secretion in turn increases weight and keeps IGFI nearly normal. This may explain the normal growth rate despite the complete lack of GH.

Body Mass Index↗

Effect of short-term testosterone treatment on leptin concentrations in boys with pubertal delay.

Testosterone administration increases growth hormone (GH) secretion and decreases the plasma leptin concentration in men. We evaluated the effect of increased GH secretion due to short-term testosterone treatment on leptin concentrations. Ten boys aged 14.8 +/- 0.2 (mean +/- SE) years with transient GH deficiency caused by pubertal delay were evaluated before and after (3 months) 4 intramuscular injections of 100 mg testosterone heptylate, given at 15-day intervals. The leptin concentration decreased from 5.4 +/- 1.3 to 3. 6 +/- 1.1 microgram/l (p < 0.001), despite a weight gain of 3.4 +/- 0.5 kg. There were significant increases in body mass index (BMI), from -0.2 +/- 0.5 to 0.2 +/- 0.5 SD, p < 0.005, in GH peak after stimulation test, from 6.3 +/- 0.5 to 21.7 +/- 2.9 microgram/l, p < 0. 0003, in plasma testosterone, from 0.6 +/- 0.1 to 6.5 +/- 1.3 microgram/l, p < 0.001, in insulin-like growth factor-I (IGF-I), from 152 +/- 21 to 330 +/- 30 microgram/l, p < 0.0001, and in IGF-binding protein-3 (IGFBP-3), from 4.2 +/- 0.5 to 5.4 +/- 0.4 mg/l, p < 0.01. But there were no changes in blood glucose (4.7 +/- 0.1 and 4.8 +/- 0.1 mmol/l), or plasma fasting insulin (9.0 +/- 1.2 and 8.1 +/- 1.3 mIU/l). The leptin concentrations were positively correlated with the BMI before (p < 0.03) and after (p < 0.04) testosterone, but not with the GH peak after stimulation, or with plasma testosterone, IGF-I or IGFBP-3. The leptin and insulin concentrations after testosterone treatment were positively correlated (p < 0.04). Thus, short-term testosterone treatment of boys with pubertal delay decreases their leptin concentrations. The lack of correlation with GH secretion or with its changes, despite the dramatic increase in GH secretion, and the lack of change in insulin are additional features suggesting that testosterone increases the leptin concentration mainly by an effect on adipose tissue.

Adolescent↗

Impaired endothelin-1 release in tilt-induced syncope.

The neurohumoral events associated with neurocardiogenic syncope remain unclear. The simultaneous assessment of changes in endothelium-dependent and independent hormones and in autonomic balance in patients with tilt-induced syncope has been incompletely studied. Forty-six healthy subjects aged between 21 and 83 years (mean +/- SEM 47 +/- 3) underwent a 30-minute head-up tilt test at 60 degrees. Fourteen subjects (10 females and 4 male subjects) exhibited syncope at 16 +/- 2 minutes into the tilt. Hemodynamics were recorded every 5 minutes and blood samples for the measure of catecholamines, endothelin-1 (ET-1), and angiotensin-II (AT-II), were drawn at baseline, and 5, 10, 15, and 30 minutes into the tilt and immediately before syncope. Heart rate variability was analyzed by 5-minute segments during the test. Both catecholamines and ET-1 levels increased consistently in response to head-up tilt in subjects able to tolerate the test. Epinephrine increased to a greater extent before syncope. In contrast, ET-1 failed to increase at any time during the tilt and just before syncope. AT-II increased at 30 minutes into the tilt only in the control group. Finally, power in high-frequency bands decreased less in the group with syncope. Thus, compared with subjects able to tolerate a head-up tilt test, patients with syncope exhibit a greater increase in adrenomedullary activation, no significant increase in ET-1 levels, and a blunting in the decrease of vagal tone before syncope. The lack of increase in ET-1 during tilt may play a role in the inability to support orthostatic stress.

Adult↗

Age- and gender-related changes in endothelin and catecholamine release, and in autonomic balance in response to head-up tilt.

1. There is an increase in circulating levels of vasoconstrictive hormones and an alteration in baroreceptor responsiveness with aging. The role of changes in endothelium-dependent and -independent vasoconstrictive hormones in relation to age and gender, with simultaneous assessment of autonomic balance in response to head-up tilt, has been incompletely studied. 2. Sixteen young [25 +/- 3 years (mean +/- SEM)] and 16 older normal volunteers (68 +/- 7 years) underwent a 30 min head-up tilt test at 60 degrees. Haemodynamics were measured every 5 min and blood samples for neurohormone measurement were drawn at baseline, 5, 10, 15 and 30 min into the test. Heart rate variability was analysed in 5 min segments at the baseline, and during the test. The younger subjects exhibited a greater increase in heart rate and diastolic blood pressure, despite lower absolute levels of noradrenaline (norepinephrine) and endothelin-1. Analysis of heart rate variability yielded a decrease in both high- and low-frequency bands in the aged; power at low-frequency decreased only in the young subjects. The age-related differences in blood pressure and noradrenaline levels were markedly attenuated in the female subjects. In addition, endothelin-1 levels and power spectral measurements at low frequency were the lowest in younger females throughout the tilt. 3. Despite attenuated cardiovascular response to tilt, both systemic adrenergic 'drive' and endothelin-1 levels increase in parallel with aging. Thus, endothelium-dependent and -independent vasoconstrictive hormone levels increase with age in the resting state and in response to neurohumoral stimulation in humans.

Adult↗

Maternal serum markers for fetal trisomy 21 screening.

A population at increased risk for fetal trisomy 21 can be defined by means of maternal serum markers. Various markers have been used since 1984, and the following have proved most valuable: hCG, free beta hCG, AFP, and estriol. Two prenatal screening periods should be distinguished: first trimester (8-14 weeks) and second trimester (14-18 weeks). Only the latter has been prospectively evaluated. In a prospective study, we assayed hCG in second trimester serum. A risk factor combining maternal age and hCG was defined and amniocentesis was offered to patients at increased risk for fetal trisomy 21. Out of 51,048 patients under 38 years of age, 135 had a trisomy 21-affected fetus. In 36,697 patients under 35, we observed 70 cases of trisomy 21, of which 41 (59%) were in the group at risk. Karyotyping was performed in 7.1% of these patients. In 11,351 patients aged 35-37 years, there were 65 cases of trisomy 21, of which 52 (80%) were in the group at risk. Karyotyping was performed in 26.8% of these patients. In our experience, parallel assaying of maternal serum AFP only detects a further 1% of trisomy 21 pregnancies for the same number of amniocenteses. These results confirm the findings of all previous prospective studies: maternal hCG screening is the most effective method of detecting trisomy 21 in the general population.

Biomarkers↗

Maternal serum human chorionic gonadotropin level at fifteen weeks is a predictor for preeclampsia.

OBJECTIVE: Our purpose was to study the correlation between maternal serum human chorionic gonadotropin levels measured at 15 to 18 weeks of amenorrhea and pregnancy-induced hypertension, preeclampsia, and small-for-gestational-age neonates. STUDY DESIGN: Prospective trisomy 21 human chorionic gonadotropin screening data from 5776 patients were examined in a retrospective investigation of the relationship between human chorionic gonadotropin and pregnancy-induced hypertension (234 cases), preeclampsia (34 cases), and small-for-gestational-age neonates (238 cases). RESULTS: Maternal serum human chorionic gonadotropin (multiples of the median) was higher in the three populations with pathologic disorders. This difference was statistically significant in patients with small-for-gestational-age neonates (p < 0.0163) and preeclampsia (p < 0.0001) but not in those with pregnancy-induced hypertension. In the preeclampsia subgroup, with a cutoff value of 2 multiples of the median, specificity was 32% and sensitivity was 10%; with a cutoff value of 1 multiples of the median, specificity was 100% and sensitivity was 50%. CONCLUSION: High maternal serum human chorionic gonadotropin levels at 15 weeks are related to a risk for preeclampsia. Depending on the human chorionic gonadotropin cutoff value, 32% or 100% of preeclampsia patients would be selected. The usefulness of preventive aspirin treatment from the fifteenth week needs more investigation in a larger multicenter study of preeclampsia.

Biomarkers↗

Development of human renal function: reference intervals for 10 biochemical markers in fetal urine.

Evaluation of fetal renal function by analysis of fetal urine sampled in utero may improve perinatal care after a prenatal diagnosis of bilateral obstructive uropathy. We provide reference intervals for 10 fetal urinary compounds and examine their variation with gestational age. Forty-one fetuses with bilateral obstructive uropathy (urine sampled between 20 and 38 weeks of gestational age) had normal, healthy values for serum creatinine (< or = 50 mumol/L) at ages 1-2 years. These cases were thus assumed to represent a reasonable approximation to healthy values. Sodium and beta 2-microglobulin concentrations significantly decreased with gestational age; calcium, ammonia, and creatinine significantly increased; glucose, phosphorus, chloride, urea, and total protein concentrations did not vary. Our results provide reference values for prenatal evaluation of fetal renal function and suggest that glomerular filtration of macromolecules and tubular reabsorption of glucose and phosphorus are mature by 20 weeks of gestation, whereas tubular reabsorption of sodium and beta 2-microglobulin increases progressively during the second half of gestation.

Biomarkers↗

[Maternal serum markers of fetal trisomy 21].

Down's syndrome is the most frequent genetic disease. Each year, in France, there are 1,100 trisomy 21-affected newborns. this chromosomal disease is the most frequent cause of mental retardation raising an important public health problem. Prenatal diagnosis of chromosomal anomalies is based on fetal karyotyping, but cannot be proposed in all situations because of the cost and the risk of fetal death due to amniocentesis. The aim of screening is to define patients at increased risk for trisomy 21. Three criteria are currently used to define an at risk-population: maternal age, ultrasound anomalies, and maternal serum markers. In France, amniocentesis is proposed to patients over 38 years of age. Ultrasound signs for trisomy 21 are often difficult to identify at routine echography. Based on a prospective study of 51,048 women under 38 years of age, we observed that maternal serum hCG at 15 weeks can detect 59% of all trisomy 21 cases while the yield for amniocentesis is 6.1%.

Adult↗

Do racial differences exist in second-trimester maternal hCG levels? A study of 23,369 patients.

In Down syndrome screening by maternal serum human chorionic gonadotropin (hCG) determination at 15, 16, 17, and 18 weeks of gestation, we prospectively examined 23,369 sera from white (21,549), North African (970), black African (525), and Asian (325) patients. When expressed as multiples of the median (MOM), no difference was observed between white, North African, and black African patients. However, higher serum hCG concentrations were noted in Asians, for whom we therefore recommend correction of hCG values before calculation of the risk of Down syndrome.

Asian People↗

Creation of experimental urethral obstruction in utero: evaluation of fetal renal function.

Management of obstructive uropathy diagnosed in utero would be markedly enhanced by the availability of a simple, safe and quantitative fetal renal function test to predict postnatal renal function. In order to allow experimental evaluation of such a parameter, we adjusted a model of complete urethral obstruction with urachal ligation in 30 fetal lambs at 79 or 99 days of gestation. The method described allows obstruction in male and female fetuses as early as 79 days of gestation, with an overall high survival rate (control: 12/14; obstructed: 23/29), although lower (6/12) when obstruction is performed early (79 days) during gestation. Consequences of obstruction were examined on the 121st day of gestation. Severe hydronephrosis, ureteral and calyceal dilatation, with or without ascites and pulmonary hypoplasia were observed in all fetuses; creatinine clearance determined in utero was decreased in both groups with obstruction (early and late) vs control group: 1.15 +/- 0.5, NS, and 0.58 +/- 0.4, p < 0.01 vs 1.61 +/- 0.8 ml/min/kg respectively. In both obstructed groups, fetuses with ascites displayed lower plasma creatinine concentration and higher creatinine clearance values when compared to fetuses without ascites. In conclusion, the experimental model of obstructive uropathy described appears efficient and easily reproducible, allowing therefore the evaluation of a predictive parameter of postnatal renal function. Our preliminary results suggest that renal fetal function is more dependent on the degree of obstruction than on the term of its creation.

Animals↗

Acute and early effects of aldosterone on Na-K-ATPase activity in Madin-Darby canine kidney epithelial cells.

The time course and mechanism of early effects of aldosterone on renal Na-K-adenosinetriphosphatase (Na-K-ATPase) activity and number of units were studied in MDCK cells. Aldosterone induced a time- and dose-dependent stimulation of Na-K-ATPase activity. The stimulatory effect of aldosterone on activity and number of pump units increased progressively and was inhibited by spironolactone. In presence of cycloheximide, the stimulatory effect of aldosterone on activity and number of catalytic sites persisted to the same extent until 30 min and decreased by 20% after 60 min. In these cells, dimethylamiloride addition during preincubation abolished the aldosterone-induced stimulation in Na-K-ATPase activity up to 60 min. In contrast, furosemide addition did not alter the effect of aldosterone on Na-K-ATPase activity. The present study demonstrates an early effect of aldosterone on Na-K-ATPase activity that can be separated into the following two successive periods: 1) increase in pump number due to insertion of presynthetized units secondary to Na entry through an amiloride-sensitive apical pathway; and 2) an increase in pump number by de novo protein synthesis.

Aldosterone↗

Protein kinase C activation causes inhibition of Na/K-ATPase activity in Madin-Darby canine kidney epithelial (MDCK) cells.

To evaluate the influence of protein kinase C (PKC) activation on Na/K-ATPase activity in MDCK cells, we studied the effect of phorbol myristate acetate (PMA) and two diacylglycerol analogues, oleoylacetylglycerol and dioctanoylglycerol, on the enzyme activity. Na/K-ATPase activity was determined by cytochemistry. PMA induced a time- and dose-dependent inhibition of Na/K-ATPase activity and at 100 ng/ml decreased the enzyme activity by 55% of the initial value. These effects were mimicked by oleoylacetylglycerol and dioctanoylglycerol, and were abolished by two inhibitors of PKC, 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7) and sphingosine. A phorbol ester that does not activate PKC, 4 alpha-phorbol 12,13-didecanoate, did not inhibit Na/K-ATPase activity. PMA inhibition persisted in the presence of cycloheximide and actinomycin D but not in the presence of amiloride. Dopamine (10 microM) inhibition of Na/K-ATPase activity was abolished in a dose-dependent manner by sphingosine. Results suggest that in MDCK cells Na/K-ATPase is an effector protein for PKC and that dopamine inhibition of its activity may be mediated by PKC.

Amiloride↗

Effects of acute cisplatin administration on renal ATPase activities and magnesium excretion of rats.

Male Wistar rats were killed 1, 2, or 4 days after a single intraperitoneal injection of cisplatin (5 mg/kg). Functional renal indices, enzymatic activities, and morphological variables were studied. One day after the injection, the treated group showed an increase in the magnesium and phosphate fractional urinary excretion (FE) vs the control group (FE Mg = 5.2 +/- SEM 0.5% vs 13.0 +/- 1.7%; P less than 0.01; and FE P = 4.7 +/- 0.7% vs 14.0 +/- 1.9%; P less than 0.01). Two days after cisplatin administration, a decrease in creatinine clearance of treated animals was found, to 0.33 +/- 0.03 vs 0.51 +/- 0.03 ml/min; P less than 0.05. Na-K-ATPase and ouabain-insensitive ATPase activities were studied in the proximal convoluted tubule, the medullary thick ascending limb of the Henle's loop (mTAL), and the distal convoluted tubule. Only in mTAL one day after the cisplatin injection was there a decrease in Na-K-ATPase activity in the treated group vs controls (1103 +/- 145 vs 1734 +/- 189 pmol Pi/mm.h; P less than 0.05). Morphological studies showed a decrease in mTAL diameters on day 1, and an increase in proximal convoluted tuble diameters at day 2 of treated rats vs controls, at 27.8 +/- 0.6 vs 31.4 +/- 0.7 microns; P less than 0.05, and 50.4 +/- 1.2 vs 47.4 +/- 0.2 microns; P less than 0.05 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗