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Biomedical subjects

G Travert

Publications and source records attributed to G Travert.

At least 37 records · Page 2Linked to original sources

[A new strategy of neonatal screening for cystic fibrosis. The association of immunoreactive trypsin and molecular biology in dried blood].

Cystic fibrosis (CF) screening by means of immunoreactive trypsin (IRT) lacks specificity: only 1 out of 12 hypertrypsinemic neonates has cystic fibrosis. We propose here to analyse the KM.19 polymorphic site in the dried blood spots as an additional test in hypertrypsinemic neonates. A blind retrospective study of 114 hypertrypsinemic samples has been performed after polymerase chain reaction. Twenty-seven of 37 CF (74%) were homozygous for allele 2 (2-2) and could have been diagnosed on the 15th day of life. Fifty-five percent of the infants tested were homozygous for allele 1 (1-1), a very rare feature in CF, conferring them a probability of being normal of 99.8%. At the moment, this test could be of great help in the CF screening, even better than the search for the delta F508 mutation for which 45.9% of CF patients are homozygous.

Cystic Fibrosis↗

Trypsin-binding immunoglobulin G and associated antigen in cystic fibrosis.

Trypsin-binding immunoglobulin G (TBIgG) is found in the sera of a high proportion of patients with cystic fibrosis. We previously reported that TBIgG preferentially binds human cationic trypsin rather than trypsin from other animal species. Binding affinity is enhanced by complex formation with bovine pancreatic trypsin inhibitor, which is known to induce characteristic conformational modifications in the active site region of the trypsin molecule. To identify the human trypsin-like antigen associated with TBIgG, we have studied the effects of conformational changes of cationic trypsin induced by limited proteolysis based on competitive binding studies. It is shown that the most likely TBIgG-related self-antigen is an 11,000-dalton fragment that is a cleavage product of the complex formed by trypsin and alpha 1-protease inhibitor. This result emphasizes the occurrence of circulating trypsinogen activation and is interpreted to be a consequence of the protease-antiprotease imbalance, which has been well documented by previous investigators in cystic fibrosis and also in other lung diseases associated with an inflammatory state.

Binding, Competitive↗

[Study of an optimal biological profile for demonstrating pancreatic involvement in acute abdominal syndrome].

The authors have studied several seric, plasmatic and urinary constituents in patients hospitalized for an acute abdominal syndrome to be able to characterize an eventual pancreatic lesion; mainly seric and urinary amylase as well as its isoenzymes, lipase, liver profile and trypsin. In acute pancreatitis, the means of the maximal increases of seric amylase, lipase and trypsin are respectively: 10.7; 21.6 and 19.2 X N (upper normal limit) whereas in chronic pancreatitis, these elevations are 6.5 X N for amylase and 9.5 XN for lipase. The authors observed at J1 (first day of hospitalisation) and at J2 an increase in seric amylase, lipase and/or liver profile respectively in 95, 90 and 25 p. cent of acute pancreatitis; in 86, 86 and 14 p. cent of chronic pancreatitis and 43, 39 and 86 p. cent of bili duct diseases. In conclusion, it appears compulsory to run a liver profile with the pancreatic enzymes (amylase and lipase) to diagnose a pancreatitis in presence of an acute abdominal syndrome.

Abdomen, Acute↗

Free triiodothyronine measured in dried blood spots from normal, low-birth-weight, and hypothyroid neonates.

Free triiodothyronine (FT3) has rarely been studied in neonates, primarily because of obvious problems in obtaining serum samples from neonates for research purposes. We adapted an analog radioimmunoassay for measuring FT3 in dried blood samples and used it to assay 361 samples selected from those collected for the screening for neonatal hypothyroidism. The mean FT3 concentration in healthy neonates on the fourth postpartum day is 2.55 pmol per liter of whole blood (SD 0.78 pmol/L, n = 145), the same as in healthy adults. Low-birth-weight infants have a decreased concentration of FT3, and this decrease is much greater in premature neonates than in infants at low weight for gestational age. In six hypothyroid newborns, the FT3 concentration was normal or increased, clearly indicating that FT3 assay is not a diagnostic tool for hypothyroidism. FT3 was barely detectable in one case of congenital galactosemia.

Humans↗

Amniotic immunoreactive trypsin in pregnancies with normal and pathological outcomes.

Immunoreactive trypsin (IRT) has been studied in amniotic fluid as a possible complementary test substance for the prenatal diagnosis of cystic fibrosis (CF). 219 normal amniotic fluids have been tested in order to establish the normal ranges from 14 to 40 gestational weeks (g.w.). The IRT level increases from g.w. 14 to 19, remains stable from g.w. 19 to 25 and then decreases rapidly to low levels. A retrospective study of 4 presumed CF fluids, as determined by abnormal alkaline phosphatase levels, showed decreased IRT values in 3 out of 4 fluids. The difference between the mean value and the normal mean was not significant. The prospective study allowed us to test 2 fluids from pregnancies affected by meconium ileus. IRT level was highly elevated, 530 times the normal mean value at g.w. 34 for a non-CF fetus and 18 times the normal mean value for a CF fetus at g.w. 31. In 4 out of 5 cases of fetal severe intra-uterine growth retardation, IRT levels appeared mildly elevated. Other abnormalities are reviewed.

Amniotic Fluid↗

[Nutritional management of neonates and infants with cystic fibrosis of the pancreas detected at birth].

From a systematic neonatal screening for cystic fibrosis in the Basse-Normandie area and to prevent disorders of the intestinal transit related to malabsorption, neonates then infants were given a semi-elemental hypercaloric diet, with supplements in nitrogen, MCT, minerals, vitamins and low in LCT. Diets were adjusted every month during a consultation using clinical and biological parameters. Results in the first 14 children showed that clinically as well as biologically, these children may remain within the normal range, avoiding the previously reported growth retardation and mineral or vitamin deficiencies. This procedure should allow an improvement in the quality of life and prognosis of such children, by maintaining adequate nutritional status.

Avitaminosis↗

Free thyroxin measured in dried blood spots: results for 10 000 euthyroid and 29 hypothyroid newborns.

We measured free thyroxin (FT4) in dried blood samples from 10 000 euthyroid and 29 hypothyroid newborns (three with transient hypothyroidism and 26 permanent). In euthyroids, the mean FT4 concentration was 16.9 (SD 4.5) pmol/L. Preterm babies had low concentrations of FT4, and values were closely related to birth weight when less than 2500 g. Assay of blood-spot FT4 appears to be specific as a test for hypothyroidism screening, yielding 0.42% false positives when a mean minus 2 SD cutoff value (8 pmol/L) was used. Correcting FT4 for birth weight further decreased the false-positive rate, to 0.07%. In all three newborns with transient hypothyroidism, FT4 was less than 8 pmol/L. In 25 of 26 permanent hypothyroids, FT4 ranged from undetectable to 5 pmol/L; in the 26th infant, who had a large ectopic gland, it was 8.2 pmol/L. We believe that FT4 assay offers an attractive improvement over total T4, whether performed as the first screening test or as a confirmatory test in thyrotropin screening programs.

Birth Weight↗

[Systematic neonatal screening for mucoviscidosis using an immunoreactive trypsin blood assay. Evaluation of 80,000 tests].

The development of a simple and reliable technique of trypsin radioimmunoassay in blood eluates allowed the neonatal screening for cystic fibrosis in a province of France. The study of the distribution of blood immunoreactive trypsin levels in 79,880 five day-old neonates led to choose a cut-off value of 900 micrograms/l; this choice gives a false positive rate of 3 in 1,000. The evolution of trypsin levels according to age during the first weeks of life leads to select a "two-phase" screening strategy: only neonates whose high neonatal trypsin levels persist after the second week of life (4 in 10,000) will undergo sweat test. Twenty-three cases of cystic fibrosis were diagnosed in this study, which gives an incidence of 1 in 3,470.

Cystic Fibrosis↗

[Radioimmunoassay of trypsin in dried blood. Importance for the neonatal detection of cystic fibrosis (author's transl)].

The demonstration of very high levels of immunoreactive trypsin in the blood of newborn infants with cystic fibrosis has provided a new way of detecting the disease soon after birth. A radioimmunoassay of trypsin in the eluate of blood dried on filter paper has now been developed. The sensitivity and accuracy of the method, as well as the good correlation observed between the values obtained and those of the conventional plasma assay, indicate that it is reliable and well adapted to the newborn. The new assay can easily be inserted into the present system of neonatal disease detection. A preliminary assessment of more than 5,000 tests enables the authors to report an early diagnosis of proven cystic fibrosis and to discuss an essential aspect of mass-detection methods: the indicence of false-positive results.

Cystic Fibrosis↗

[Maternal alpha-fetoprotein. Its levels in the eluate of dried blood for screening antenatally defects in the closure of the neural tube (author's transl)].

Taking levels of alpha-feto-protein serially from the mother's blood between the 16th and 18th week of pregnancy gives rise to the possibility of screening more than 80 per cent of cases of anancephaly and spina bifida. Because of the seriousness and the frequency of these fetal malformations (12 in 10,000 deliveries) in our district, routine antenatal screening would be worth while. Because of this we suggest that a radioimmune technique for measuring the levels of AFP in dried blood eluate should be carried out. It is as reliable as measuring the levels in blood serum. The way of obtaining the sample that is used makes it suitable for mass screening. We have established the normal values of AFP measured by our method between the 15th and 22nd weeks of pregnancy. These make it possible to define the upper limits of warning that are suitable for screening on a regional basis. During this study we found a case of anencephaly in which the level of maternal AFP was significantly higher than the limits we had worked out.

Female↗

Trypsin-binding immunoglobulin G in cystic fibrosis, allergic, and normal children.

Using a simple and sensitive radioassay, we have determined the frequency of trypsin-binding (TB) immunoglobulin G (IgG) as a function of age in cystic fibrosis (CF) patients, in allergic patients, and in control subjects. These IgGs appear during the 1st years of life. Their frequency is maximum between 3 and 20 years of age and decreases during adulthood. In allergic children TBIgG appears later than in CF children and the maximum frequency (32%) is intermediate between those observed in CF and in control children (66 and 19.6%, respectively). We suggest that an endogenous form of trypsin is involved in the phenomenon.

Adolescent↗