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Biomedical subjects

J E Toublanc

Publications and source records attributed to J E Toublanc.

At least 19 recordsLinked to original sources
PubMed1994

[Alpha fetoprotein in congenital hypothyroidism before and during treatment].

BACKGROUND: Screening for congenital hypothyroidism (CH) is an opportunity to investigate maturation by measuring alphafetoprotein (AFP). PATIENTS AND METHODS: Blood AFP was measured in 73 full-term infants (controls), 22 infants with permanent CH and 19 with a transient form (FT) of hypothyroidism. It was also measured in mothers of the two groups with hypothyroidism. AFP was measured by RIA and its value was compared to those of FT4, TSH and bilirubin. RESULTS: Blood AFP was higher in patients with CH with significant differences between patients who had jaundice or not, but AFP was not significantly different in FT patients and controls. Initial values of AFP in both CH and FT population was correlated to the levels of AFP in their mothers. Under treatment with 7.5 micrograms/kg/day of l-T4, AFP levels remained increased at T15, then gradually normalized at T30-T60. The log of AFP was correlated to TSH levels between T15 and T60 but was not correlated to FT4 levels. Preliminary results at one year of age show that IQ seems better in infants with early normalization of AFP. CONCLUSIONS: Prolonged follow-up is necessary to assess the possibility that initial kinetics of AFP under therapy have a prognostic value for estimating the quality of outcome.

Adult↗
PubMed1992

Prenatal prediction of androgen insensitivity syndrome using exon 1 polymorphism of the androgen receptor gene.

Exon 1 polymorphism of the androgen receptor (AR) gene is characterized by a (CAG)n(CAA) repeat at position 172 following the translation start codon. The aim of this study was to determine whether AR gene exon 1 polymorphism could be used to perform prenatal diagnosis in high risk families with complete or partial androgen insensitivity syndrome. After enzymatic amplification of a 1 kilobase exon 1 fragment, each DNA was simultaneously digested by MspI and PstI restriction enzymes. After electrophoresis on a 15% electrophoresis on a 15% acrylamide gel or a 6% Nusieve gel, we measured the size of the obtained fragments and determined the number of CAG repeats since a 282 basepair fragment corresponds to 21 CAG. We previously showed that the number of CAG repeats within the AR gene exon 1 in 23 families with complete or partial androgen insensitivity syndrome was 19 +/- 4. By this method, we detected heterozygosity in 50% of the mothers. We present here 2 exclusion prenatal diagnoses using exon 1 polymorphism of the AR gene. Family A presented a boy with a severe form of partial androgen insensitivity syndrome. The mother had 2 uncles with ambiguous genitalia. In family B, the affected child had a complete androgen insensitivity syndrome. In both families, analysis of the AR gene exon 1 polymorphism of the trophoblastic DNA showed the presence of the normal maternal X chromosome. The parents decided to carry on the gestation. In family A, the newborn had normal male external genitalia. In family B, sonography confirmed the presence of normal male external genitalia. These data suggest that exon 1 polymorphism of the AR gene could be prenatally used to predict androgen insensitivity syndrome.

Androgens↗
PubMed1992

Molecular analysis of the androgen receptor gene in 52 patients with complete or partial androgen insensitivity syndrome: a collaborative study.

In patients with androgen insensitivity syndrome (AIS), RFLP study of the androgen receptor gene made it possible to analyze whether deletions or mutations could be responsible for abnormalities in androgen responsiveness. We studied RFLPs of DNA from 25 46,XY patients with partial AIS (PAIS), defined as a concentration of androgen receptor in genital-skin fibroblasts less than 340 fmol/mg DNA, and DNA from 27 46,XY patients with complete AIS (CAIS) with no detectable androgen receptor site. DNA samples were digested with BamHI, EcoRI, HindIII and TaqI restriction enzymes and hybridized with three cDNA probes covering the three domains of the androgen receptor. When we had the maternal and an unaffected brother's DNA, we analyzed the two androgen receptor gene polymorphisms described, the HindIII and the exon 1 CAG repeat polymorphisms, in order to distinguish the two maternal X chromosomes, and to detect carriers of AIS. We did not find any large deletion among the 52 patients. We observed a heterozygous mother in 3 of 14 families studied with the HindIII polymorphism, and in 12 of 25 families using the exon 1 CAG repeat polymorphism. This study suggests that in AIS, abnormalities in androgen receptor response could be related to point mutations or microdeletions rather than to gross structural alterations of the androgen receptor gene. Furthermore, unless the point mutation has been described, exon 1 and HindIII polymorphism studies would enable the identification of carriers in 50% of families, and the prenatal diagnosis of AIS.

Androgens↗
PubMed1992

The sole presence of the testis-determining region of the Y chromosome (SRY) in 46,XX patients is associated with phenotypic variability.

Four cases of XX patients with testis development are reported. The aim of this study was to describe their clinical features and to see if there was any relationship between phenotypes and the presence of Y material. Several human Y-derived sequences including the SRY probe were used to analyze the DNA of the patients. Yp material including the pseudo-autosomal region and SRY was detected. The cases reported in this study confirm that XX true hermaphrodites cannot be distinguished from XX males on the basis of their genotypes. There is no relationship between clinical and anatomical phenotypes and the presence of Y material. SRY does not warrant a complete and normal testis differentiation. Although similar in some features with Klinefelter's syndrome patients, XX males exhibit specific clinical manifestations due to the lack of Y-specific genes.

Adolescent↗
PubMed1992

Comparison of epidemiological data on congenital hypothyroidism in Europe with those of other parts in the world.

The actual worldwide incidence of congenital hypothyroidism (CH) is based on the results of screening in parts of the world where screening is mandatory, i.e. most of Europe, USA, Canada, Cuba, Australia, New Zealand and Japan. In other parts of the world, some indications are given by the results of pilot studies. In Europe, mean overall incidence (1985-1990) for the countries included in our inquiry is 1/3801--in each country for the same period: Austria 1/3,930, Belgium 1/3,750, Czechoslovakia 1/6,037, Denmark 1/3,777, Finland 1/3,969, France 1/4,132, FRG 1/3,827, Greece 1/3,314, Hungary 1/5,632, Israel 1/3,152, Italy 1/3,150, The Netherlands 1/3,723, Norway 1/3,069, Portugal 1/3,139, Spain 1/3,216, Switzerland 1/3,913, UK 1/3,398 and Turkey (pilot study 1989-1992) 1/2,943. In comparison, the figures for the USA for the whole country are similar for the mean overall incidence (1988-1990): 1/4,119. But large variations exist between the states, the reasons of which are perhaps related either to technical problems or to the ethnic background in each state. In Canada and Japan, modifications of screening procedures have led to similar figures for the last years in our possess, Canada (1986-1988) 1/3,884 and Japan (1990) 1/3,856. The figures (mean overall incidence) for Cuba (1987-1991) 1/2,325, for Australia (1985-1990) 1/1/3,331 and for New Zealand (1987-1990) 1/4,496 are quite comparable. So in these countries where the screening is established, no great variations are noted as in certain parts of the world with pilot studies: Argentine (Buenos Aires; 1985-1990) 1/4,407, Chile (1991-1992) 1/2,514, Brazil (Porto Alegre; 1987-1991) 1/4,429.(ABSTRACT TRUNCATED AT 250 WORDS)

Congenital Hypothyroidism↗
PubMed1992

Screening for Y-derived sex determining gene SRY in 40 patients with Turner syndrome.

In Turner patients, the presence of a Y chromosome or derivative Y is correlated with the risk of gonadoblastoma induction. "Marker" chromosomes originating from Y, may not show characteristic fluorescence and then be very difficult to identify by conventional cytogenetic techniques, although they still predispose the patients to gonadal tumors. Using polymerase chain reaction of the gene from the sex-determining region of the Y chromosome, we screened 40 Turner patients (thirty seven 45X and three 45X,46XX) for the presence of Y chromosomal DNA. We were able to identify karyotypically unrecognized Y chromosome material in 1 patient out of the 40 studied. In this patient mild clinical and biological hyperandrogenism was observed. Reliability of our technique was ascertained by the detection of the expected 648 base pairs amplified DNA fragment in all normal male controls as well as in 3 Turner patients with confirmed 45X,46XY mosaicism. Despite the low frequency of unrecognized Y chromosome material (1 case over 40 in our experience), our data suggest that polymerase chain reaction of the gene from the sex-determining region of the Y chromosome is worthy of being performed in Turner patients considering the potential risk of the presence of a Y chromosome.

Adolescent↗
PubMed1991

Etiologies of late puberty.

An expected lack of pubertal development can be due to an already diagnosed disease. The diagnosis of an unexpected lack of puberty is a difficult task. We have analyzed the etiologies of late puberty in 106 adolescents: 68 boys aged over 15 years and 38 phenotypic girls aged over 13 years. According to their clinical and biological (gonadotropin) data, they were classified in 3 groups. In the first group, hypergonadotropism was observed only in 19 females; pure gonadal dysgenesis was found in 2 cases with 46,XY, in 2 with 46,Xdel(Xq) karyotypes and 9 cases were 46,XX constitutions; 2 sisters had also blepharophimosis; in 3 cases the ovarian failure was due to autoimmune disease, and 1 case, genetically male, had 17 alpha-hydroxylase deficiency. The second group had gonadotropin insufficiency and consisted of 68 adolescents, 57 males and 11 females, with low gonadotropin levels: 33 were anosmic; in the boys, cryptorchism was present in 68% and micropenis in 31%; 38 had a familial history of hypogonadism, the transmission of which was matrilineal in 16, patrilineal in 13 and recessive autosomal in 7. The third group had low or low-normal gonadotropin levels: 22 cases of constitutional delay of puberty (11 cases in both sexes), demonstrated by further normal puberty during the follow-up. No clinical marker and familial history in 50% were noted.

Adolescent↗
PubMed1991

[Study of antibody-dependent cell mediated cytotoxicity and thyroid growth blocking antibodies in congenital hypothyroidism].

Antibody-dependent cell mediated cytotoxicity (ADCC) and thyroid growth immunoglobulin blocking (TGI block) which have been found in autoimmune thyroiditis in adults, as well as TSH receptors binding inhibitory antibodies (TBI ab) and antimicrosomal (Mc ab) and antithyroglobulin (Tg ab) antibodies were search in 42 mothers-infants pairs called at hospital after a positive screening for congenital hypothyroidism. The etiologic diagnoses were: 12 athyreosis, 12 ectopies, 7 anatomically normal glands and 11 transients. Tg ab and Mc ab were measured by commercial hemagglutination tests, TBI ab were determined using a radio ligand assay. ADCC in a 51Cr release assay by human thyroid cells in culture and TGI block by incorporation of 3H-thymidine using the same cells. Results were 38% for TBI ab in infants mainly in patients with dysgenesis without any concordance between mothers and infants. ADCC were found in 24% and TGI block in 24% with respectively mothers-infants concordance of 90% and 84%. Five mothers had autoimmune diseases (2 thyroiditis, 2 Graves' diseases and 1 insulin-dependent diabetes). Beside these rare cases of maternal diseases, the significantly high number of antibodies without any expression in the mothers suggests that autoimmunity plays a role in the etiology of congenital hypothyroidism.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

A possible common origin of "Y-negative" human XX males and XX true hermaphrodites.

We have studied nine patients aged 1 month to 16 years with 46, XX karyotypes and testicular tissue. Some of these patients were followed through puberty. Phenotypically, two presented normal and seven abnormal external genitalia (AG). Among this latter group, four showed hypospadias and three true hermaphroditism (TH). The endocrine data were similar in all three groups: testosterone levels were within normal limits during puberty, decreasing in adulthood; gonadotrophin levels were above the control values at mid puberty. Histologies of the two sub groups of AG patients were identical up to 5 years of age and presented differences when compared with controls, regardless of the ovarian part of the ovotestis. However, in patients older than 8 years, germ cells disappeared and dysgenesis became obvious. In one patient, the ovarian zone of the gonad was detected only after complete serial sections of the removed gonad were examined. Southern blot analysis with Y-DNA probes displayed Y-specific material for the classic 46 XX males and a lack of such sequences for all patients with AG and TH. Based on these findings, we postulate that 46, XX males with AG and 46, XX TH may represent alternative manifestations of the same genetic defect. These data together with those concerning familial cases of 46, XX males with AG and 46, XX TH suggest an autosomally (or pseudoautosomally) determined mechanism.

Adolescent↗
PubMed1990

[Psychomotor and intellectual development in 52 children with congenital hypothyroidism screened at birth. Factors likely to have an effect on prognosis].

Follow-up was obtained for at least 4 years in 52 children (40 F, 12 M) who presented with congenital hypothyroidism, detected by TSH screening at 5 days of age and persisting at the 3th-5th postnatal week. Eight had athyreosis, 33 an ectopic thyroid gland and 11 an anatomically normal thyroid. Treatment began at day 29 +/- 12 (1 SD) with I-T4 solution, 5-7 micrograms/kg/day and was followed in order to obtain immediately T4 and FT4 blood levels in the high normal range, with normal TSH at least from age 6 months. Mental development was evaluated at age 0.5, 1 and 2 years with the Brunet-Lézine scale, and at 4 years with the Termann-Merill test. Thirty of them were reevaluated at age 7 years with the WISC-R test. The results of these tests were all in the normal range, with individual differences, the range being 85 to 145 at 4 years and 95 to 133 at 7 years, not different from those obtained in age-matched controls and in the normal siblings of the patients at 4. The WISC-R test at 7 years did not show differences between verbal and performance levels. Its results were correlated with those of the TM test performed at age 4 years in the same 30 patients: r = 0.75, p less than 0.01. School level at 7 years was normal for age in these 30 hypothyroid children.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1989

The effects of treatment combining an agonist of gonadotropin-releasing hormone with growth hormone in pubertal patients with isolated growth hormone deficiency.

The final height of patients treated with growth hormone for isolated growth hormone deficiency has, up to now, been subnormal, with a mean below -2 SD in the series reported, an insufficient height at the onset of puberty and a more or less accelerated bone maturation during puberty being two important factors of the poor results. A long-acting analogue of gonadoliberin, Trp6-GnRH, has been given to GH-treated patients with isolated growth hormone deficiency at the time they reached pubertal stage 2, in combination with unchanged doses of GH, for one year in 11 and for two years in 7 of them. It resulted in an increase in the height age/bone age ratio and a reduction of the height insufficiency for bone age. The increase was slight but significant after one year, and fair after two years, in spite of reduced annual growth rate. Post-analogue follow-up in 5 patients with continued GH treatment showed a good development of growth and of puberty. It is concluded that combination of the long-acting Trp6-GnRH analogue and GH for 1-2 years in patients with isolated growth hormone deficiency whose puberty starts with a very insufficient height may be an appropriate way to improve their growth parameters. Studies with increased doses of GH or increased frequency of injections could help to optimize the results. Several years of follow-up are needed for demonstrating the results on final height.

Adolescent↗
PubMed1988

Mode of inheritance in familial cases of primary gonadotropic deficiency.

The mode of inheritance of primary gonadotropic deficiency was studied in 38 children and adolescents. 92% of this population was male with high frequencies of undescended testes (80%) and micropenis (31%). Anosmia was present in 61% of the patients aged more than 5 years and was a frequent genetic marker in the families. Inheritance was matrilineal in 18, X-linked dominant or autosomal dominant in 6. In 13 cases, the transmission was patrilineal and evoked autosomal dominant inheritance. An autosomal recessive transmission was likely in 7 patients. The data agree with the suggestion of multiple modes of inheritance of congenital gonadotropic deficiency, and clearly show the wide range of expressivity of the disorder.

Adolescent↗
PubMed1988

Endocrine and immunological findings in cryptorchid infants.

In cryptorchid infants, significantly decreased mean levels of plasma testosterone and luteinizing hormone (LH) were found between the ages of 30 and 120 days. The levels of testosterone and LH were significantly correlated. No significant difference was found between infants with bilateral or unilateral cryptorchidism. After 120 days there was no longer any significant difference between cryptorchid infants and controls. No significant change in plasma follicle-stimulating hormone (FSH) was found. These data suggest that subnormal secretion of LH could be the primary abnormality in a proportion of boys with so-called common cryptorchidism. Our studies using LH-releasing hormone and human chorionic gonadotropin stimulation tests in older infants and children agree with the data obtained by measurement of basal plasma hormone levels during the first months of life. Anti-gonadotroph antibodies were found in the sera of approximately 50% of the cryptorchid children and infants studied, using an immunofluorescence technique. A study of 17 mothers and their infants gave concordant results in 16 pairs, 9 with and 7 without antibodies. This lead us to speculate on the possible role of maternal autoantibodies as a cause of partial gonadotrophin deficiency in the perinatal period and thus of testicular maldescent. As cryptorchidism is a syndrome, these findings do not mean that a similar mechanism is operative in all cases. However, these data do suggest that alternatives to the classical anatomical view of the descent and nondescent of the testes should be considered.

Age Factors↗
PubMed1988

[Long-term fate of pituitary dwarfs treated with growth hormone].

A questionnaire having been mailed to 50 hypopituitary patients aged 18 to 36 years (m 21.7 +/- 3.4) previously treated with human growth hormone for at least 3 years, 44 answers have been received. The final height is 2.1 +/- 0.9 standard deviations below the average. However 57% of the patients consider it is sufficient. The smallness is felt as a handicap by 20% only of these adults, though 88% had suffered for it during their adolescence. The treatment is retrospectively considered as useful and acceptable by 68%, heavy but useful by 25%, heavy and useless by 7%, without correlation with the results. Only 41% are satisfied with their school achievements. However, more than two thirds of patients had severe school difficulties at the time of onset of the treatment. Actually 75% of the patients are professionally qualified, among whom 36% have achieved high school, and most have an educational level similar to that of their parents or even higher. But 41% only have an employment, 27% are still students and 32% are unemployed. The way of life of the young hypopituitary adults is severely affected: 6 only are married or living with a mate, 11 only write they have occasional sexual experiences, 16 remain completely alone. In contrast, leisure activities are good in more than 90%. A score taking all these data into consideration to evaluate their way of life shows, among the 43 complete answers to the questionnaire, 16% with excellent results, 49% with a rather good social status and 35% with poor final result.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

The pituitary-gonadal axis in cryptorchid infants and children.

We have attempted to document in cryptorchid children that there is an LH deficiency and a secondary deficiency of testosterone. We have shown a diminished LH peak after LH-RH in cryptorchid versus normal infants (P less than 0.05). The postnatal surge of testosterone is significantly low (P less than 0.001) in permanent cryptorchids versus infants with secondary testicular descent, whose levels are similar to those in controls. In permanent cryptorchids during the same period (0-4 months), LH and testosterone levels were significantly lower (P less than 0.01 and P less than 0.05 respectively) than in infants with secondary descent, and the levels of testosterone and LH were correlated in both populations. In children, a low basal level of LH was observed at pubertal stage P2, and LH peak after LH-RH was significantly reduced at stages P1 and P2 (P less than 0.01 and P less than 0.05 respectively). The post-stimulatory levels of testosterone after hCG were reduced at the same stages (P less than 0.01, P less than 0,05), and the two levels were correlated (P less than 0.01). No differences are seen for LH and testosterone afterwards. It has been possible to show by immunofluorescence on pituitary cells the occurrence of antigonadotropin cell antibodies (AGCA) in more than 50% of our patients, with no relation to age and no correlations between endocrinological data and the presence or absence of AGCA. The relatively low success rate of hCG treatment, mainly in young children, and of GnRH irrespective of the regimen of treatment, does not exclude the role of primary LH deficiency in cryptorchidism.

Child↗