Voltage-controlled spectral shift of porous silicon electroluminescence.
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Biomedical subjects
Publications and source records attributed to F Muller.
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A prospective study of maternal serum human chorionic gonadotrophin (hCG) measurement for the selection of pregnancies with an increased risk of fetal trisomy 21 was undertaken in 24,000 pregnancies from 1 January 1989 to 31 December 1990. Maternal serum was sampled at 15-18 weeks of gestation. hCG was measured in one laboratory, with one technique. This 'hCG high level' technique was developed for this screening. Amniocentesis was offered to each woman with a maternal serum hCG level above the cut-off. The follow-up of the pregnancies is known in 92 per cent of cases. The combination of hCG values and maternal age gave a detection efficiency of 63 per cent for trisomy 21 with rates of amniocentesis of 30 per cent for patients aged 37 years. 20 per cent for patients aged 35 or 36 years, and 5 per cent for patients under 35 years of age. Based on this prospective study, an individual risk was calculated combining the serum hCG value and maternal age. Seventy-four per cent of trisomy 13, trisomy 18, triploidy, and 5p-deletion were detected either in the same selected group of women or in combination with ultrasonography performed when hCG values were very low. The follow-up study showed that women who had high or low hCG values represented a group at high risk for fetal or perinatal death.
The effectiveness and costs of prenatal screening programmes for Down's syndrome using maternal serum markers will vary significantly depending on the biological cut-off values chosen in order to select women, at each maternal age, who will be sent for amniocentesis. On the basis of the first French prospective study of human chorionic gonadotropin (hCG) measurement in maternal serum, this paper shows that the screening protocol currently used in France, where hCG cut-off values are defined in order to offer amniocentesis to women of all ages with a 1 per cent fetal risk of Down's syndrome, would detect 64.06 per cent of all cases of trisomy 21 at birth and would be highly profitable for the French social security system. On the basis of a representative sample of 100,000 pregnant women, the total costs of screening would reach $8,302,000 but would generate net potential savings of $32,186,000 in terms of life-long costs of care for trisomic 21 children which would be 'avoided' by termination of pregnancy following a positive diagnosis of Down's syndrome. Economic assessment shows that cost-benefit analysis would justify lower hCG cut-off values and a higher detection rate of fetal Down's syndrome (74.45 per cent) than the current French protocol. This paper concludes that it is ethical and value-laden issues, such as the consequences for women and couples of false positives and false negatives of screening, rather than economic and financial arguments that may set limits to the utilization of screening for Down's syndrome using maternal serum markers like hCG.
Maternal serum free beta (hCG) levels are elevated (median 2.20 MOM) in the first trimester of pregnancy in 38 Down syndrome cases as compared with appropriate controls. This observation may form the basis for its use as a marker in screening for Down syndrome in the first trimester. Altered levels of the free beta analyte are observed in pregnancy conditions or complications other than Down syndrome.
The value of maternal serum pregnancy-associated plasma protein (PAPP)-A in screening for Down syndrome in early pregnancy was assessed using stored samples. Seventeen cases of Down syndrome and 66 unaffected control pregnancies were studied. The median PAPP-A level in the cases was 0.42 multiples of the expected value in controls (p < 0.0001). Eleven cases (65 per cent) had levels less than half the expected value compared with only six controls (9 per cent). A commercial assay kit is now needed so that prospective screening with this marker can begin.
Serum human chorionic gonadotrophin (hCG) can be assayed in specimens obtained by percutaneous fetal blood sampling to check for the absence of maternal blood or amniotic fluid contamination. In order to assess the accuracy of this approach, we measured serum hCG in 44 pure fetal blood samples obtained by intracardiac puncture. The mean fetal serum hCG concentration was 52 IU/l, and the ratio of maternal to fetal serum hCG concentration never exceeded 1.1 per cent, which represents the smallest contamination rate detectable by this method.
OBJECTIVE: To investigate the ability of fetal urinalysis to predict in utero the renal function of children with bilateral uropathy who survive to the second year of life. METHODS: This was a prospective cohort study of 100 consecutive patients with prenatal diagnosis of bilateral uropathy who underwent fetal urine sampling. Fetal urinary concentrations of sodium, chloride, calcium, phosphorus, ammonium, urea, creatinine, glucose, proteins, and beta 2 microglobulin were measured. Prenatal findings were matched with renal function of survivors at 1-2 years. The single end point was serum creatinine, which was considered abnormal when greater than 50 mumol/L (0.56 mg/dL) during the second year of life. RESULTS: Elevated serum creatinine was found in 17 of 42 children with isolated uropathy who survived more than 1 year. For prediction of elevated serum creatinine during the second year of life, the fetal urinary concentration of beta 2 microglobulin was both specific (0.83) and sensitive (0.80); sodium, chloride, and urea levels were sensitive (0.70 or greater) but lacked specificity (less than 0.65); and fetal urinary glucose, phosphorus, calcium, ammonium, and total proteins were specific (0.70 or greater) but lacked sensitivity (0.65 or less). CONCLUSIONS: Our results provide a new approach to prenatal management of congenital obstructive uropathies by identifying those fetuses at risk for survival with suboptimal renal function. These fetuses might benefit from intrauterine therapy. In contrast, no attempt at prenatal uro-amniotic shunting should be made when a spontaneously good outcome is predicted by fetal urinalysis.
Introduction of maternal serum markers for prenatal screening of Down's syndrome implies a redefinition of the criteria used for identifying at risk women for screening by amniocentesis, which are currently based on maternal age. On the basis of the first French prospective study of human chorionic gonadotropin measurement in maternal serum as a predictor of Down's syndrome, this paper shows that a screening policy combining maternal age with hCG measurement was more cost-effective than one relying on maternal age alone. A cost-benefit analysis (using the "avoided" lifelong costs of care for a trisomic 21 child that are allowed by prenatal screening) would justify lower hCG cut-off values and an higher detection rate of Down's syndrome (74.5%) than other decision rules based on alternative principles such as: equalization to 1% of fetal risk of Down's syndrome for access to amniocentesis at all maternal ages or equalization to 1/1000 of fetal risk of Down's syndrome among women not undergoing amniocentesis. However, results of the cost-benefit analysis are very sensitive to other factors such as the cost associated with loss of a normal fetus due to iatrogenic risk of amniocentesis (false positives of hCG). Ethical and value-laden issues that necessarily underlie economic evaluation of screening programmes, as well as other decision rules based on equalization of acceptable risk for each maternal age, are discussed.
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We previously suggested that an activation defect of pancreatic proteolytic zymogens in newborns suffering from cystic fibrosis (CF) might contribute (by an adaptative-like process) to the significant increase of the serum trypsin level observed in the disease at birth. To give support to this hypothesis we studied two pancreatic enzymes: trypsin 1 (IRT) and chymotrypsin A (IRChT) by noncompetitive enzyme immunoassays in amniotic fluids taken at 17-18 weeks of pregnancy. In normal fluids (102), the levels of the two enzymes were widely dispersed between 5 and 100 micrograms/L. A similar pattern was observed for the fluids with a 1 in 4 risk of CF with a normal outcome (24). In contrast, the levels of pancreatic enzymes in the fluids with affected fetus (40) were always below 45 micrograms/L for IRT and 55 micrograms/L for IRChT and most of them were under 20 micrograms/L for both enzymes. The molecular forms of IRT and IRChT in amniotic fluids were studied by gel filtration. In amniotic fluids with affected fetus, a major form of IRT was eluted in a position consistent with the elution of proteins around 25 kDa and two peaks of IRChT were eluted at 75 kDa and 25 kDa. These patterns are similar to those observed in normal serum when zymogens are present and are quite different from the patterns obtained by gel filtration of amniotic fluids with normal outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
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 hyperechogenicity 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.
Introduction of maternal serum markers for prenatal screening of Down's syndrome leads to a redefinition of the criteria used for identifying at risk women (i.e. in France, mainly based on maternal age of 38 and over). Effectiveness and costs of prenatal screening of Down's syndrome using such maternal serum markers will vary depending on the biological cut-off values defined, at each maternal age, to identify the population of pregnant women that will be sent to amniocentesis. On the basis of the first French prospective study of the use of human chorionic gonadotropin (hCG) measurement in maternal serum as a predictor of an increased risk of Down's syndrome, this paper shows that a screening policy combining maternal age with hCG measurement is more cost-effective than screening on the basis of maternal age alone. However, final decisions about hCG cut-off values should take into account the complex ethical dilemmas involved, especially the potential consequences of "false positives" and "false negatives", of this marker.
The Pond-Nuki dog model of osteoarthritis has characteristics which seem to mimic the human disease in early stages, particularly with respect to progressive changes in the cartilage matrix. Aggregating proteoglycans were studied using novel extraction and ultracentrifugation methods designed to separate very large macromolecules. With these methods two large peaks of proteoglycan (PG) aggregates (PGA-1 and PGA-2) were separated in preparative amounts and were shown to have unequivocal differences in composition in many respects. The profiles of these peaks have been studied as a function of joint location, topographic site, cartilage layer, presence of cartilage atrophy versus osteoarthritis, as well as treatment of the animals with various agents. Both link protein (essential for forming link-protein stabilized aggregates) and hyaluronate are required to regenerate normal aggregate profiles from the deficient aggregate fractions obtained from osteoarthritic cartilage. Canine proteoglycan link-stabilized aggregates (PGA-2) are confined to the middle and deep zone of cartilage. We believe that their reduction or elimination in the Pond-Nuki model results from a disturbance or loss of functional link protein (and hyaluronate), thereby weakening the middle and deep cartilage layers.
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Three hundred and twenty-six French families with a cystic fibrosis-affected child who were referred for prenatal diagnosis were analysed by sibship size: 74.2 per cent of the couples had no further pregnancies to term after the affected child, who was deceased in 34.6 per cent of cases. These couples were followed prospectively after prenatal diagnosis and 77 had two or more consecutive pregnancies with prenatal diagnosis. The aim of these couples was to succeed in constituting a family with two normal children.
Prenatal diagnosis of hypophosphatasia was made by alkaline phosphatase (ALP) assay on a chorionic villous sample taken in the first trimester. Very low activities of the LBK isoenzymes indicated an affected fetus. Diagnosis was confirmed at 12 weeks of gestation by measurement of LBK isoenzyme activities in fetal bone tissue. In control chorionic villous samples an inverse relation was observed between LBK and placental ALP percentage during gestational age. High LBK ALP activities are observed in decidual tissue. Chorionic villous tissue must not be sampled after 12 weeks of gestation and decidual tissue must be excluded from the sample.
As chronic hypertension shifts the lower limit of cerebral blood flow (CBF) autoregulation to higher pressure levels, we studied the effects of the angiotensin converting enzyme (ACE) inhibitor, perindopril on mean arterial pressure (mean BP), basal CBF, and CBF autoregulation in awake renovascular hypertensive (2 kidneys, 1 clip model) and spontaneously hypertensive rats (SHR). Blood pressure was measured via a chronically implanted arterial cannula and CBF by hydrogen clearance. Chronic renovascular hypertension, like spontaneous hypertension, caused a marked shift in the lower limit of CBF autoregulation but did not alter basal CBF. In SHR, acute administration of perindopril did not diminish CBF in spite of the fact that BP fell to a level below the lower limit of CBF autoregulation (determined by hypotensive hemorrhage). Chronic treatment of renovascular hypertensive rats with perindopril normalized BP and restored CBF autoregulation.
Treatment of young rats with vitamin D3 plus nicotine has been proposed as a model of cardiovascular calcium overload. This treatment produced a 20-35-fold increase in the calcium content of the aorta, a compliance vessel, and this increase was accompanied by a 1.6-fold elevation of pulse pressure. In aortic rings, the maximal inhibition by the endothelium-dependent vasodilator, carbachol, of vasoconstriction induced by noradrenaline decreased from 90% in controls to 61% in treated animals. There were significant correlations between aortic calcium content and pulse pressure and aortic calcium content and carbachol-induced relaxation. In conclusion, the vitamin D3 plus nicotine model may be useful for the study of the role of calcium overload in decreased arterial compliance coupled with endothelial injury.