A cooling jacket to reduce tubular damage during kidney transplantation: evaluation of a prototype in the pig model.
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Biomedical subjects
Publications and source records attributed to F Muller.
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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.
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%.
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Fetal urinary concentrations of insulin-like growth factor I (UIGF-I) and binding protein 3 (UIGFBP-3) were determined in patients with prenatal diagnosis of bilateral obstructive uropathy. Patients were retrospectively assigned to three groups, on the basis of outcome: group 1, termination of pregnancies (n = 11) with sonographic evidence of severe oligohydramnios or renal dysplasia, confirmed at histological examination; group 2, patients (n = 10) with postnatal plasma creatinine > 50 mumol/l at the age of 1 year (1 yr-pCreat); and group 3, patients (n = 16) with 1 yr-pCreat < or = mumol/l. The results show a significant increase in UIGF-I and UIGFBP-3 in groups 1 (18,159 +/- 9083 pg/ml; 2657 +/- 669 ng/ml) and 2 (1574 +/- 847 pg/ml; 176 +/- 50 ng/ml) in comparison with group 3 (35 +/- 6 pg/ml; 21 +/- 2 ng/ml). UIGF-I and UIGFBP-3 were significantly correlated with postnatal plasma creatinine, and were both sensitive (90 per cent; 80 per cent) and specific (88 per cent; 88 per cent) for prediction of elevated 1 yr-pCreat (> 50 mumol/l). Fetal urinary IGF-I and IGFBP-3 are increased in severe fetal bilateral obstructive uropathy, possibly reflecting tubular dysfunction or/and increased synthesis consequent upon fetal kidney injury. Their predictive value for postnatal renal function needs further assessment.
OBJECTIVE: Fetal hyperchogenic bowel is associated with a variety of conditions, the incidence of which has yet to be studied. STUDY DESIGN: The outcomes of 182 cases of fetal hyperechogenic bowel were reviewed. Screening for maternal toxoplasmosis, fetal karyotyping, and amniotic fluid digestive enzyme assays were performed in all cases. Eight mutations associated with cystic fibrosis were analyzed in 116 cases. RESULTS: Of 135 newborns, 121 were normal, but nine underwent surgery for gastrointestinal obstruction, three had cytomegalovirus or parvovirus infection, one had a triple X chromosome, and one died from sudden infant death syndrome. In utero fetal death was observed in 24 cases. Elective termination of pregnancy was performed in 23 cases for associated anomalies. CONCLUSIONS: Hyperechogenic fetal bowel was associated with increased risk for adverse outcome. Prenatal management should include ultrasonographic surveillance, fetal karyotyping, amniotic digestive enzyme assays, and screening for cystic fibrosis and infectious disease.
The object of this study was to explore the role of folate in the pathophysiology of neural tube defects (NTD). Maternal and fetal serum and red blood cell folate were assayed in 14 cases of NTDs and compared with 14 controls with other malformations and matched for gestational age (range 18-36 weeks). In mothers of NTD fetuses, serum folate (5.2 ng/ml), red blood cell folate (294 ng/ml) and the folate methylation rate (65%) were significantly lower than in controls (6.6 and 399 ng/ml, respectively, and 77%). However, the fetal folate status was similar in cases and controls. In the NTD group, folate metabolism was altered in the mothers but not in the fetuses. Therefore, a normal folate placental transfer can be assumed in this group. In addition, it could be speculated that decreased maternal folate methylation might be involved in the pathogenesis of NTDs.
The median maternal serum free beta human chorionic gonadotropin (hCG) multiple of the median (MOM) of 480 Down syndrome cases in the second trimester was 2.64, significantly greater than the reported median MOM of intact hCG (p < 0.0001). In 234 of these cases from retrospective and prospective studies, the effectiveness of maternal serum free beta hCG was evaluated in combination with alpha-fetoprotein (AFP) and maternal age in second-trimester Down syndrome screening. Down syndrome detection in the gestational age range of 14-16 weeks was 82 per cent. In all gestational weeks (14-22), a 77.7 per cent Down syndrome detection rate was achieved. In prospective screening of 44,272 patients under the age of 35 years, 69 per cent of Down syndrome cases were detected (73 per cent in gestational weeks 14-16). The false-positive rate for the prospective study was 3.8 per cent. The use of free beta hCG combined with maternal serum AFP and maternal age-related risk for Down syndrome in a screening population (i.e., women under 35 years) yields an improved detection efficiency over other protocols.
Maternal serum levels of human chorionic gonadotrophin and its subunits (intact, alpha, and free beta h CG) and pregnancy-associated plasma protein A (PAPP-A) were measured in 279 women between 8 and 14 weeks' gestation. This group included 23 pregnancies in which the fetus had Down syndrome (DS), diagnosed either at birth or during the second trimester (n = 17) or from chorionic villus sampling (CVS) (n = 6). Normal medians were determined from the 258 apparently normal pregnancies. The median levels of intact hCG (1.4 MOM) and free beta hCG (2.1 MOM) were significantly raised, whereas the median level of PAPP-A (0.39 MOM) was significantly lower in the DS pregnancies when compared with the control group. Levels of alpha hCG were similar in both the control and the DS pregnancies. Analysis of samples taken prior to 14 weeks' gestation demonstrated that only PAPP-A (0.34 MOM) was significantly altered in DS pregnancies. However, after the exclusion of DS cases diagnosed at CVS, the median intact hCG (1.56 MOM), free beta hCG (2.27 MOM), and alpha hCG (1.8 MOM) were all raised in DS pregnancies. This emphasizes the problem of the interpretation of biochemical markers when DS cases are diagnosed at CVS.
Second-trimester distributions of the free beta human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) levels in 420 twin and 19 triplet pregnancies were measured and compared with the distributions in 6661 singleton pregnancies. On average, the levels of both analytes were twice as high and over three times as high in triplets. Eight sets of twins discordant for Down's syndrome showed elevated levels of free beta hCG and reduced levels of AFP after correction of the multiple of the median for the presence of a twin pregnancy. Screening for Down's syndrome using the twin correction of the multiple of the median is expected to achieve a 51 per cent detection rate at a 5 per cent false-positive rate using these two markers.
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.
The diagnostic value of amniotic fluid gamma-glutamyl-transpeptidase (GGTP) and intestinal alkaline phosphatase (iALP) was evaluated in 55 patients who underwent amniocentesis for karyotyping because fetal gastric or small bowel dilatation had been detected by ultrasound. Gastrointestinal malformation was confirmed in 46 cases and there was no gastrointestinal anomaly in nine cases. Prenatal ultrasound was suggestive of gastroduodenal dilatation in 34 cases (group I) and small bowel dilatation in 21 cases (group II). In group I, amniotic fluid GGTP above the 99th percentile was 71 per cent sensitive and 100 per cent specific for a true anatomical defect of the digestive tract (mainly duodenal atresia). In group II, high levels of GGTP and/or iALP were 69 per cent sensitive and 83 per cent specific for a fetal digestive tract anomaly. In other words, when digestive tract dilatations were diagnosed by prenatal sonography, abnormal amniotic fluid enzyme activities were strongly suggestive of such an anomaly, the possibility of which was not precluded by normal amniotic fluid iALP and GGTP activities. But amniotic fluid digestive enzyme activities do not help in defining the prognosis.
Low digestive enzyme activities in human amniotic fluid can be observed in normal and disease-affected pregnancies: cystic fibrosis, trisomy 21, intestinal atresia. Amniotic fluids were analyzed by proton nuclear magnetic resonance (NMR) spectroscopy in order to specify prenatally the etiology of low digestive enzyme activities observed at 17-18 weeks of amenorrhea. A total of 114 amniotic fluid samples were collected at 17-18 weeks of amenorrhea. Karyotyping and assays of digestive enzyme activities were performed in all cases. Samples were divided into six groups according to enzyme activities and pathology. Proton spectra were retrospectively recorded. Many compounds, such as amino acids and carboxylic acids, were detected by NMR. The same resonance intensities (normalized to creatinine) were observed in the six groups. Nevertheless, an unidentified resonance at 1.05 ppm was detected in seven out of 13 cases of cystic fibrosis affected fetuses. The NMR spectra demonstrated the stability of the amniotic fluid composition at 17-18 weeks of amenorrhea, even when the fetus was affected by a disease such as trisomy 21 or intestinal atresia. The resonance associated with most cases of cystic fibrosis should be further investigated.
This paper concerns the prediction of fetal Down's syndrome in pregnant women. Down's syndrome is the most common congenital cause of severe mental retardation. We elaborate two predictive functions of trisomy 21, combining maternal age and a maternal serum marker. We evaluated them by means of receiver operating characteristic (ROC) curves which give a representation of sensitivity and specificity of a prediction model when varying the cutoff of the predictor on the whole spectrum. Since normal statistical methods for comparison of ROC curves rely on distributional assumptions which were not verified, we used bootstrapping of ROC curves as a check for the statistical significance of differences between the areas under the curves.
OBJECTIVES: To precisely evaluate fetal renal function in cases of bilateral fetal urinary tract obstruction, we analyzed fetal urine metabolites by nuclear magnetic resonance spectroscopy. STUDY DESIGN: Fifty-six specimens of fetal urine samples in utero were retrospectively analyzed by proton nuclear magnetic resonance. Group 1 (n = 21) consisted of survivors for > or = 1 year with normal serum creatinine (< 50 mumol/L), for group 2 (n = 17) of survivors with abnormal serum creatinine (> 50 mumol/L), and group 3 (n = 18) of those with bilateral histologic dysplasia associated with fetal (termination of pregnancy) or neonatal death. RESULTS: A specific nuclear magnetic resonance profile was obtained for each of the three groups of renal function. A two-dimensional representation of alanine-valine and valine-threonine concentrations allows clear differentiation between the three degrees of renal function, with a sensitivity and specificity of 88% and 86%, respectively. CONCLUSIONS: In fetal bilateral urinary tract obstruction a fetal urine nuclear magnetic resonance profile allows an accurate identification of renal function at birth.
In order to evaluate renal function, fetal urine was sampled in 27 fetuses with urinary tract obstruction diagnosed by ultrasonography. Amino acid concentrations were measured retrospectively. On histological examination performed after termination of pregnancy, five fetuses were found to have bilateral renal dysplasia (group 1). Eleven fetuses developed renal failure after birth: at one year, plasma creatinine concentration was over 50 mumol/l (group 2). Renal function was normal in the 11 other infants (group 3, plasma creatinine concentration at one year < 50 mumol-1). Statistically significant between-group differences were seen in fetal urine amino acids concentrations. However, there was an overlap of values in the three groups and individual amino acid concentrations could not be used predictively.
The development of ultrasonography has allowed the antenatal diagnosis of various forms of obstructive uropathy. The diagnosis of urinary tract dilatation is now possible by the 15th week of pregnancy. More recently, the study of foetal urine biochemistry has defined the prognostic factors of the course of postnatal renal function. The authors define and limit the current indications for the various antenatal interventions on the basis of the combination of antenatal ultrasonography and foetal urine biochemistry.