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Biomedical subjects

F Muller

Publications and source records attributed to F Muller.

At least 55 records · Page 3Linked to original sources

Development of human fetal kidney in obstructive uropathy: correlations with ultrasonography and urine biochemistry.

In utero urethral obstruction results in bilateral hydronephrosis and severe fetal and post-natal morbidity and mortality. Obstetrical management depends on the indirect evaluation of fetal renal function by ultrasonography and biochemical analysis. No direct evaluation of the severity and possible reversibility of renal lesions is available. In this paper we analyzed kidneys from 34 fetuses (14 to 37 gestational weeks) in which (1) isolated bilateral urinary tract obstruction had been detected in utero by sonography, and (2) the severity of sonographic and biochemical prognostic indicators led to the indication of termination of pregnancy or to perinatal death. Pure hydronephrosis was observed in two young fetuses [14 and 20 gestational weeks (GW)] and was associated with regressive changes in two others. In contrast, a wide spectrum of dysplastic renal lesions was present in 30 fetuses and was classified into four subgroups according to the association of dysplasia, hypoplasia and cysts. They had the following characteristics in common: (1) premature cessation of nephrogenesis assessed by the medullary ray counting method; (2) early disappearance or myofibroblastic differentiation of metanephric blastema; (3) early increase in interstitial mesenchyme with widespread expression of alpha-smooth muscle actin by mesenchymal cells; (4) frequent absence of classical criteria of dysplasia (nests of cartilage were observed in only 5 fetuses); (5) an identification, based upon the detection of alpha-smooth muscle actin expression, of the muscular phenotype of mesenchymal cells encircling primitive ducts. In conclusion, (1) the value of prognostic markers in fetuses less than 20 GW should be reconsidered; (2) after 20 GW there is a good correlation between markers predicting poor prognosis and the severity of renal lesions; (3) hypoplasia with disappearance of blastema cells, dysplasia and early interstitial fibrosis are evidence of the irreversibility of renal lesions and preclude any possibility of new nephron formation; (4) these findings suggest that most surgical in utero procedures are performed when irreversible renal lesions have developed.

Actins↗

Prenatal diagnosis of neural tube defect before 12 weeks' gestation: direct and indirect ultrasonographic semeiology.

We describe the direct and indirect ultrasonographic features of a case of lumbar open spina bifida. The spinal defect was the prominent feature at 10 weeks + 5 days' gestation; however, cranial signs including narrowing of the frontal bones and flattening of the occiput were helpful at 12 weeks. This 'acorn' sign is likely to precede the 'lemon' sign, describing scalloping of the frontal bones at a later gestation. The diagnosis of spina bifida was confirmed by electrophoresis of the amniotic fluid, which showed an abnormal migration of acetylcholinesterase. Postmortem ultrasound examination of the same fetus proved useful in refining the diagnosis and also revealed the presence of the Arnold-Chiari malformation. Development of ultrasound screening in the first trimester of pregnancy should allow further evaluation of these findings. It seems reasonable to confirm such an early diagnosis by electrophoresis of the amniotic fluid as an alternative to ultrasonographic confirmation at 13-14 weeks.

Acetylcholinesterase↗

Biochemical markers of trisomy 21 in amniotic fluid.

In a study of amniotic fluid from 91 Down's syndrome cases and 240 controls, we have shown that the median values of four biochemical markers (AFP, total hCG, free beta hCG, and unconjugated oestriol) in the amniotic fluid of pregnancies affected by Down's syndrome on the whole reflect those observed in the maternal serum of affected cases. The median MOM for AFP was lower than average (0.56), as was that for unconjugated oestriol (0.55), whilst those for total hCG (1.82) and free beta hCG (2.10) were increased on average. The width of the distribution of marker levels in amniotic fluid is similar to that in serum for free beta hCG and total hCG but between 1.5 and 2 times wider for unconjugated oestriol and AFP. Analysis of data by fetal sex showed a significantly higher median MOM in female control cases compared with male controls for the analytes free beta hCG, total hCG, and unconjugated oestriol, but not for AFP. Amongst the Down's syndrome cases, this trend was not statistically significant and we cannot confirm a previous study which reported that elevated levels of amniotic fluid total and free beta hCG were associated only with female fetuses.

Adult↗

Stability of gamma-glutamyltransferase activity in calf sera after refrigerated or frozen storage.

OBJECTIVES: To examine stability of -glutamyltransferase (GGT) activity in stored serum from neonatal calves. ANIMALS: 10 commercial beef calves between 36 and 60 hours old. PROCEDURE: Serum samples were obtained from the calves, and each sample was divided into 8 aliquots. Serum GGT activity was measured on day 0 (fresh) and days 1, 2, 3, and 4 of refrigerated storage (4 C) and weeks 1, 2, and 3 of frozen storage (-20 C). RESULTS: Serum GGT activities for each of the refrigerated aliquots did not significantly differ from day zero, with serum GGT activity (expressed as a percentage of initial activity) > 99% on all 4 days. Serum GGT activity in frozen aliquots decreased significantly after 1 and 2 weeks of frozen storage, 97 and 98%, respectively; however, this decrease in GGT activity was not biologically significant. The observed GGT activity did not decrease significantly in the samples stored frozen for 3 weeks; these samples retained 99% of initial activity. CONCLUSION: The observed stability of serum GGT activity indicates that serum may be obtained, stored, and batch processed at a later time. This stability during storage is important to the success of a bovine passive transfer monitoring program based on GGT activity.

Animals↗

A search for interstellar oxiranecarbonitrile (C3H3NO).

We report a search in cold, quiescent and in 'hot core' type interstellar molecular clouds for the small cyclic molecule oxiranecarbonitrile (C3H3NO), which has been suggested as a precursor of important prebiotic molecules. We have determined upper limits to the column density and fractional abundance for the observed sources and find that, typically, the fractional abundance by number relative to molecular hydrogen of C3H3NO is less than a few times 10(-10). This limit is one to two orders of magnitude less than the measured abundance of such similarly complex species as CH3CH2CN and HCOOCH3 in well-studied hot cores. A number of astrochemical discoveries were made, including the first detection of the species CH3CH2CN in the massive star-forming clouds G34.3+0.2 and W51M and the first astronomical detections of some eight rotational transitions of CH3CH2CN, CH3CCH, and HCOOCH3. In addition, we found 8 emission lines in the 89 GHz region and 18 in the 102 GHz region which we were unable to assign.

Astronomy↗

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↗

[Cooling shell in renal transplantation. Thermometric evaluation of a prototype].

We have developed a cooling system for renal transplants designed to eliminate the second period of warm ischaemia corresponding to the vascular anastomosis phase of renal transplantation. This is an autonomous and independent system which forms a shell around the transplant. Following application of the system, cooling is achieved by refrigeration of a Multitherm sponge contained in the wall of the shell. The thermometric characteristics of a prototype were evaluated in vitro and in vivo in pigs. This system allows the kidney to be preserved at a temperature of less than 10 degrees C for 1 hour without inducing any risk of lesions of the renal surface. Human applications should be developed in the near future.

Anastomosis, Surgical↗

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↗

Fetal urinary insulin-like growth factor I and binding protein 3 in bilateral obstructive uropathies.

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.

Electrolytes↗

Hyperechogenic fetal bowel: an ultrasonographic marker for adverse fetal and neonatal outcome.

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.

Amniocentesis↗

Maternal-fetal folate status and neural tube defects: a case control study.

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.

Case-Control Studies↗