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Biomedical subjects

F Muller

Publications and source records attributed to F Muller.

At least 109 records · Page 6Linked to original sources

[Strategies for selection of pregnancies with increased risk of fetal trisomy 21].

The main indications for cytogenetic prenatal diagnosis have been based on pregnancies with an increased risk of chromosomal anomaly. Advanced maternal age has been the most important criterion and presently 60% of women of 38 yr and over undergo prenatal diagnosis. Fetal malformations detected by ultrasound resulted in the selection of a group in which approximately 10% chromosomal anomalies were detected. An effort has been made to describe sonographic signs indicative of Down's syndrome. Maternal serum biochemical markers constitute another approach for screening. Human chorionic gonadotropin is the most discriminant test. Combining maternal and hCG cut-off levels, it is possible to detect approximately 70% of trisomy 21% in women aged between 30-38 yr.

Adult↗

[Fortuitous discovery in echography of an isolated fetal intra-abdominal hyperechogenic mass. 87 cases].

Having seen 87 cases we will now attempt to refine the management to be carried out when intra-abdominal hyperechogenic masses are found in the fetus. Before the 20th week of amenorrhoea (47 cases) amniocentesis can be used to study the digestive enzymes to determine the fetal karyotype. The normal results for intestinal enzymes makes it possible to rule out fetal cystic fibrosis. Three karyotype abnormalities were found in this series. After the 20th week (40 cases) intestinal enzymes cannot be interpreted. The diagnosis of cystic fibrosis then must rely on Delta F 508 mutation; but the absence of this mutation does not exclude cystic fibrosis. When ultrasound signs of intra-abdominal hyper-echogenicity are found the diagnosis of cystic fibrosis should not be thought of first, because in this series the majority of fetuses who had this sign were born without any malformation. Four cases of cystic fibrosis that were confirmed have been found but equally there were other serious malformations, three chromosome abnormalities, four intestinal atresias, ten unexplained intra-uterine deaths and one case of biliary duct atresia.

Amniocentesis↗

Angiotensin II stimulates angiotensinogen synthesis in hepatocytes by a pertussis toxin-sensitive mechanism.

The role of intracellular messengers in the stimulatory effect of angiotensin II on angiotensinogen synthesis and secretion in hepatocytes was examined. Angiotensinogen secretion was not influenced by modulators of intracellular calcium (calmidazolium, A 23187, Bay K 8644, methoxamine). In contrast, agents decreasing intracellular cAMP (angiotensin II, guanfacine) stimulated, and those increasing cAMP (isoproterenol, glucagon, forskolin) depressed angiotensinogen secretion. An inverse relationship was also observed between cAMP and angiotensinogen mRNA. Pretreatment of hepatocytes with pertussis toxin abolished the stimulation by angiotensin II. It is concluded that angiotensin II-induced stimulation of angiotensinogen synthesis is initiated by inhibition of adenylate cyclase.

Adenylate Cyclase Toxin↗

A single chorionic gonadotropin assay for maternal serum screening for Down's syndrome.

A simple enzyme immunoassay measuring human chorionic gonadotropin in undiluted maternal serum has been developed in order to be used as a prenatal screening test for Down's syndrome. A retrospective study of maternal serum sampled during pregnancies associated with trisomy 21 shows that with a 5% amniocentesis rate determined on a single test, the detection rate of trisomy 21 would be around two-thirds of the affected pregnancies. A prospective study of 9040 pregnant women under 38 years has confirmed the usefulness of the assay.

Adult↗

Chronic treatment with the angiotensin I converting enzyme inhibitor, perindopril, restores the lower limit of autoregulation of cerebral blood flow in the awake renovascular hypertensive rat.

Chronic hypertension shifts the lower limit of cerebral blood flow autoregulation to a higher pressure level. Although acute administration of angiotensin converting enzyme inhibitors restores the lower limit of cerebral blood flow autoregulation the chronic effects have not received much attention. We studied the effect of the angiotensin converting enzyme inhibitor, perindopril, on mean arterial pressure, basal cerebral blood flow and cerebral blood flow autoregulation in renovascular hypertensive (two-kidney, one clip model) and normotensive male Wistar rats. Seven weeks after renal artery clipping or sham operation rats received daily intraperitoneal injections of perindopril. The dose was increased from 1 to 8 mg/kg over the first 4 weeks until blood pressure was normalized. Chronic renovascular hypertension caused a marked shift in the lower limit of cerebral blood flow autoregulation but did not alter basal cerebral blood flow. Treatment of hypertensive rats with perindopril normalized blood pressure and restored cerebral blood flow autoregulation. Chronic treatment of normotensive rats with perindopril increased basal cerebral blood flow. In conclusion, chronic treatment of renovascular hypertensive rats with perindopril causes a shift in the lower limit of cerebral blood flow autoregulation towards the value observed in normotensive rats.

Angiotensin-Converting Enzyme Inhibitors↗

[Antenatal diagnosis and management of congenital chylothorax].

A case of congenital chylothorax diagnosed with prenatal ultrasonography is described. Thoracocentesis was performed at 33 weeks of gestational age but recurrence of chylothorax, increasing hydramnios and subcutaneous oedema made cesarean section necessary at 37 weeks. Mechanisms of chylothorax during the fetal life and its management before and after delivery are discussed.

Adult↗

[Antenatal diagnosis of obstructive uropathies].

Many cases of low or bilateral obstructive uropathy due to malformations lead to death, either in utero or at birth, as the absence of diuresis leads to oligoamnios, which in turn causes hypoplasia of the lungs that does not allow neonatal survival. The associated chromosomal anomalies or multiple malformations also have harmful effects. These severe prenatal forms had not been taken into account for pediatric statistics, and were previously not studied. Thus it proved essential for prenatal medicine not to be content with arriving at diagnoses, but rather to try and foresee the prognosis of the abnormalities revealed by assessing the renal function of the fetus in each case. A number of data on fetal urine, such as the sodium, 2-microglobulin or calcium levels, make this assessment possible. Correlations between the fetal urinary parameters and the renal function in the child at age one have been established. These criteria now allow distinguishing the fetuses that will not survive from those that will have renal insufficiency and, finally, from those whose renal function will be normal at age 1.

Constriction, Pathologic↗

[Digestive physiopathology of the fetus].

The evolution en enzymatic activity in the amniotic fluid follows the various stages of development of the gastrointestinal tract during pregnancy. Before 12 weeks of amenorrhea, no enzymatic activity can be detected, as this period corresponds to the persistence of the pharyngeal and anal membranes. At 13-14 weeks, a very high level of enzymatic activity is suddenly observed in the amniotic fluid, reaching its peak at 16-18 weeks. This phase corresponds to the opening of the pharyngeal membrane, the appearance of swallowing and the opening of the anal membrane. After 18 weeks, the digestive enzyme level progressively decreases until 22-24 weeks, after which date no gastrointestinal enzymatic activity can be evidenced in normal fetuses (probably because of functional anorectal obstruction). We have determined the enzymatic anomalies related to some gastrointestinal deformations (duodenal atresia, cystic fibrosis, atresia of the bile ducts, anorectal atresia).

Amniotic Fluid↗

First-trimester amniotic fluid acetylcholinesterase electrophoresis.

Acetylcholinesterase (AChE) gel electrophoresis was performed on normal amniotic fluids obtained at 4-15 weeks of pregnancy. Until 8 weeks, all the fluids were AChE-positive; the percentage of positive specimens decreased from 9 until 11 weeks and no positive specimen was found after 12 weeks. This method may allow early prenatal diagnosis of neural tube defects after the 12th week.

Acetylcholinesterase↗

Genetic heterogeneity between two clinical forms of cystic fibrosis evidenced by familial analysis and linked DNA probes.

CF heterogeneity has been evidenced from both clinical and genetic observations. At least two clinical forms of CF are easily distinguishable: CF with meconium ileus and CF without meconium ileus. The results of prenatal diagnosis have shown that the recurrence rates of CF are different in these two clinical forms. Molecular analysis of Restriction Fragment Length Polymorphisms (RFLPs) tightly linked to the cystic fibrosis (CF) gene defined several types of CF and normal chromosomes in a French sample of 64 families with CF. The CF mutation is tightly linked to one XV-2C and KM19 RFLPs haplotype but is differently linked to J3.11 RFLP alleles, depending on whether or not the clinical form of CF is associated with ileus. A distortion of the segregation ratio observed between normal and CF haplotypes in the families with ileus could explain the high recurrence rate of CF in such families.

Alleles↗

Vasoactive intestinal peptide and its receptors in fetuses with cystic fibrosis.

Fetuses were investigated to establish whether vasoactive intestinal peptide (VIP) and its receptors are involved in the basic biochemical defect causing cystic fibrosis (CF). The intestine was used as a target for the disease and the liver as control. The immunoreactive and biologically active VIP contents of the colon and lower part of the small intestine were 1.5-2.5 times higher in CF fetuses than in controls. In control and CF intestinal mucosa, there was no change in the Scatchard parameters of the 125I-labeled VIP binding sites (Kd = 4.7-6.1 X 10(-11) M; Bmax = 268-280 fmol/mg protein for the high-affinity sites), in the two molecular components constituting the cross-linked 125I-VIP binding (Mr = 66,000 and 30,000), or in the pharmacological properties and functional characteristics of the VIP receptors activating the G proteins-adenylate cyclase system (Ka = 0.7 X 10(-9) M VIP). Similar results were obtained in liver. These findings suggest that neither VIP nor its receptors are involved in CF intestine. The possible involvement of other effectors related to the VIP pathway in CF intestine, including the release of VIP and adenosine 3',5'-cyclic monophosphate signal-transduction cascade, are presented.

Adenylyl Cyclases↗

Microvillar enzyme assays in amniotic fluid and fetal tissues at different stages of development.

A systematic study of microvillar enzyme activities in the amniotic fluid in correlation with their values in different fetal tissues during development has been undertaken. Microvillar enzymes appeared in the amniotic fluid at the time of disappearance of the anal membrane, 12-13 weeks, and declined from the 18th week until the 24th week. The study of fetal tissues and fluids has shown that gamma-glutamyltranspeptidase is mainly of liver origin. The significant decrease of the activities of these amniotic fluid enzymes has been the basis of prenatal diagnosis of cystic fibrosis. These assays may be useful for the diagnosis of certain digestive tract abnormalities at later stages of pregnancy.

Alkaline Phosphatase↗

Primary health care: on measuring participation.

This paper considers the problems of finding measurements for the two major principles of primary health care (PHC), equity and participation. Although both are of equal importance, the authors concentrate on the assessment of participation. A methodology is put forward to define indicators for participation in health care programmes as how wide participation is on a continuum developed for each of the five factors which influence community participation. These factors are: needs assessment leadership, organisation, resource mobilisation and management. By plotting a mark on a continuum which is defined as wide and narrow at the extremes and is connected with all other marks in a spoke arrangement, it is possible to describe a baseline for participation in any specific health programme. This baseline can be used to compare the same programme at a different point in time, to compare observations by different evaluators, and/or to compare perceptions of different participants in the same programmes. A case study provides an example of how the indicators might be used. These indicators focus on the breadth of participation and not its potential social impact, an area which is recognised to be critical for future research.

Community Participation↗

Interest of biology in the management of pregnancies where a fetal malformation has been detected by ultrasonography.

The results of two French collaborative studies are reported with respect to chromosomal and biochemical analyses following the ultrasonographic detection of a fetal anomaly. Overall, chromosomal anomalies were observed in 14.8%, ranging from 8.6% in isolated single malformations to 40.5% in multiple fetal malformations associated with intrauterine growth retardation. Acetylcholinesterase (AChE) electrophoresis was performed on the amniotic fluid of 64 cases of ultrasonographically diagnosed isolated hydrocephalus. 8 cases of previously unsuspected open neural tube defects were diagnosed by AChE. Digestive microvillar enzyme assays were useful in the precise diagnosis of suspected gastrointestinal anomaly. The correlation of the results of ultrasonography and chromosomal and biochemical analyses is the basis for the diagnosis and the prognosis of pregnancy.

Amniocentesis↗