Biomedical subjects
Publications and source records attributed to P Sagot.
Explore the source record for details and available documents.
Oral-facial-digital syndrome type 1 (OFD1) is characterised by an X linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, tooth, and distal abnormalities, polycystic kidney disease, and central nervous system malformations. Large interfamilial and intrafamilial clinical variability has been widely reported, and 18 distinct mutations have been previously reported within OFD1. A French and Belgian collaborative study collected 25 cases from 16 families. OFD1 was analysed using direct sequencing and phenotype-genotype correlation was performed using chi2 test. X inactivation studies were performed on blood lymphocytes. In 11 families, 11 novel mutations, including nine frameshift, one nonsense, and one missense mutation were identified, which spanned nine different exons. A combination of our results with previously reported cases showed that the majority of mutations (65.5%) was located in exons 3, 8, 9, 13, and 16. There was phenotype-genotype correlation between (a) polycystic kidney disease and splice mutations; (b) mental retardation and mutations located in exons 3, 8, 9, 13, and 16; and (c) tooth abnormalities and mutations located in coiled coil domains. Comparing the phenotype of the families with a pathogenic mutation to families with absence of OFD1 mutation, polycystic kidneys and short stature were significantly more frequent in the group with no OFD1 mutation, whereas lingual hamartomas were significantly more frequent in the group with OFD1 mutation. Finally, an X inactivation study showed non-random X inactivation in a third of the samples. Differential X inactivation between mothers and daughters in two families with high intrafamilial variability was of particular interest. Slight phenotype-genotype correlations were established, and X inactivation study showed that skewed X inactivation could be partially involved in the pathogenesis of intrafamilial clinical variability.
Preeclampsia, which complicates 3-8% of pregnancies, is one of the leading causes of neonatal morbidity and mortality. Its pathophysiology remains unclear. The aim of the present study was to investigate the presence and the role of beta2- and beta2-adrenergic receptors (ADRB2 and ADRB3, respectively) in human placental arteries and to assess the influence of preeclampsia on ADRB responsiveness. SR 59119A, salbutamol, and isoproterenol (ADRB3, ADRB2, and nonselective ADRB agonists, respectively) induced a concentration-dependent relaxation of placental artery rings obtained from women with uncomplicated or preeclamptic pregnancies. SR 59119A-induced relaxation was unaffected by the blockade of ADRB1 and ADRB2 by 0.1 microM propranolol but was significantly decreased by the blockade of ADRB1, ADRB2, and ADRB3 by 10 microM propranolol. Both SR 59119A and salbutamol were associated with a significant increase in cAMP production that was significantly inhibited by pretreatment with 0.1 microM propranolol only for salbutamol. SR 59119A-induced relaxation (E(max) = 28% +/- 5% vs. 45% +/- 4%, respectively) and cAMP production (2.7 +/- 0.5 vs. 4.9 +/- 0.4 pmol/mg of protein, respectively; P < 0.01) were decreased in arteries obtained from preeclamptic compared to normotensive women. Both ADRB2 and ADRB3 transcripts were expressed at the same level between arteries from normotensive and preeclamptic women. Western blot analysis, however, revealed a decreased expression of the ADRB3 immunoreactive protein in arteries from preeclamptic compared to normotensive women. We suggest the presence of functional ADRB2 and ADRB3 in human placental arteries. Even if preeclampsia is associated with an impairment of the ADRB3 responsiveness, ADRB3 agonists may have future pharmaceutical implications in the management of pregnancy-related disorders.
The phenotype of mosaic variegated aneuploidy (MVA) syndrome is characterized by severe microcephaly, growth deficiency, mental retardation, and mild physical anomalies. The MVA syndrome is associated with mosaicism for several different aneuploidies involving many different chromosomes with or without premature centromere division (PCD). To date 28 cases of MVA syndrome have been reported. We report the first case of MVA syndrome without microcephaly. The clinical features in our patient included craniofacial dysmorphic features, growth retardation, and developmental delay. Cytogenetics analyses and FISH studies showed multiple aneuploidy with trisomy 18, 19, and 8, respectively in blood lymphocyte and fibroblasts without PCD. This case is compared with the other of MVA syndrome previously reported in literature. From this case report, we suggest that microcephaly is not mandatory for the diagnosis of MVA syndrome.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Approximately 30% of women diagnosed with cervical cancer are in their childbearing years. Prenatal care provides an excellent opportunity for cervical cancer screening. The incidence of abnormal Pap smear has been reported in 5-8% of pregnant women. But we must know that Pap smears have cytologic modifications because of pregnancy. All abnormal smears have to be referred to colposcopic examination. The squamocolumnar junction is visualized in almost 100% of cases. The sensitivity of colposcopy is nearly 87% with complete concordance in 72.6%. Colposcopically directed biopsies have a good correlation with the final diagnosis with very minimal risks for both mother and fetus. The high rate of complications (hemorrhage, abortion, premature labor) and residual lesions in half of cases do not encourage conization during pregnancy. The final treatment is carried out after delivery. The only absolute indication for conization in pregnancy is to rule out microinvasive disease or make the diagnosis of invasive carcinoma when such a diagnosis will alter the timing of delivery but also when there is a no satisfactory colposcopy and a high-grade Pap smear. In these cases conization is performed for diagnostic and not therapeutic purpose. We must be aware of the high rate of loss of follow-up (6-33%).
Explore the source record for details and available documents.
We report a case of a subhepatic cystic mass diagnosed in utero by antenatal ultrasonography (US) at 15 weeks' gestation which subsequently proved to be a communicating duodenal duplication. In this male foetus, the differential diagnosis was choledochal cyst, congenital biliary atresia, foregut duplication or omentum cyst. Neonatal US examination lead to a diagnosis of duodenal duplication, also confirmed by barium gastrointestinal series. He was operated on day 8 and recovered uneventfully. We discuss the accuracy of antenatal US in the diagnosis of such right upper quadrant cystic masses. Now that antenatal findings are becoming increasingly sensitive in the detection of foetal anomalies, and parents need to be informed about the suspected pathology and its prognosis, we tried to determine, in the light of this case and a review of the literature, how antenatal US findings can offer more accuracy in the diagnosis of duodenal duplication.
The lipid composition of germ cell membranes is considerably modified during spermatogenesis, sperm maturation and capacitation. Some of these modifications are caused by exchanges between soluble lipid donors or acceptors and cell membranes. The aim of this study was to assess whether significant lipid transfers between lipoprotein structures are detectable in human seminal plasma. Phospholipid and cholesteryl ester (CE) transfer activities were measured by specific fluorescence and isotopic assays. Seminal plasma samples did not display significant CE transfer. Substantial levels of phospholipid transfer activity were detected in all samples studied, levels were approximately 25% of the phospholipid transfer activity measured in human blood plasma. Concordantly, CE transfer protein was not detected in seminal plasma, while the presence of the phospholipid transfer protein (PLTP) was confirmed by Western blot analysis. Enzyme-linked immunosorbent assay indicated that seminal PLTP concentrations represented 25% of the concentration measured in blood plasma. Blockade of phosphatidylcholine and phosphatidyl-ethanolamine transfer by a 60 min, 56 degrees C heating step or with anti-PLTP antibody revealed that PLTP accounts for almost 80% of the phospholipid transfer activity present in seminal plasma. As shown by gel-permeation chromatography and Western blot analysis, seminal PLTP activity was partially associated with prostasomes. Significantly higher PLTP activity levels were measured in seminal plasma samples with low seminal vesicle secretions. The latter observation may reflect the sustained secretion of active PLTP that is diluted in a variable volume of PLTP-free seminal vesicle secretion. In conclusion, human seminal plasma displays significant phospholipid transfer activity due to the presence of active PLTP.
It is not unusual for respiratory specialists to be called to deal with respiratory problems in pregnancy. However, some conditions, such as tocolysis-induced pulmonary edema, although common, are largely unknown to our specialty. We report on the cases of three pregnant women, who developed pulmonary edema in the context of tocolysis with the intra-venous infusion of B-agonists. In all three patients, tocolysis was required because contraction developed well before term. Triple pregnancy was present in one patient. In another patient, mechanical ventilation was required. The outcome was good with full recovery in all three cases.
Epidemiological surveys concerning snakebites were carried out in the savannah area of North Cameroon according to two methods. A retrospective survey carried out in 5 hospitals or dispensaries covering a 3- to 8-year period according to locality was followed by a prospective survey in 4 of these health centres lasting 1 or 2 years according to location. These studies involved respectively 1,710 and 359 patients. The annual incidence varied between 50 and 250 envenomations per 100,000 inhabitants according to year and locality. The average annual incidence was close to 200 cases. Echis ocellatus corresponded to 85% of the identified snakebites. Lethality ranged from 0 to 23.9% of the envenomations. It significantly decreased during the prospective study due to the systematic use of antivenoms administered through the venous route (IPSER Africa then FAV Afrique). During the prospective study, we observed that 25% of snakebite victims did not present any symptoms: 71% presented an oedema, 63% a coagulopathy and less than 5% a necrosis. The population at risk involved people aged 15 to 44 years, especially males. Most of the bites had occurred during agricultural activity. In the cotton zone, more than 40% of the envenomations took place during the 3 months of the field preparation and cotton sowing. Elsewhere, the snakebites were spread out over time with a clear increase during the rain season.
Porencephaly is a rare central nervous system (CNS) abnormality that can be caused by an intraparenchymal destructive process or a developmental defect. Here we report on a prenatal ultrasound diagnosis of complex CNS abnormalities including agenesis of the corpus callosum, agenesis of the cerebellar vermis, bilateral hydrocephaly, and bilateral porencephaly in fetus at 33 weeks' gestation. The diagnosis of familial orofaciodigital syndrome type I (OFD I) was raised after fetal autopsy, clinical examination of the family, and the X-linked dominant inheritance pattern. This is the fourth report of porencephaly in association with OFD I. We discuss the difficulties in genetic counselling since OFD I shows variable expressivity of the phenotypic features. Furthermore, we emphasize the importance of a detailed ultrasound examination after a prenatal diagnosis of porencephaly.
To assess the regional perinatal network of Burgundy (20 obstetrical units; 18,000 births/year), discharge abstracts are collected for all mothers and all neonates. Discharge abstracts are expanded with some additional data. According to the French law, data are rendered anonymous in each hospital before their transmission to the teaching hospital for statistical analysis. The linkage of all anonymous information concerning a patient is obtained. Moreover, this specific procedure allows the linkage of data concerning each mother and her corresponding neonate. This study shows that after an expanded data quality control, the linkage between data of the mothers and their infants is obtained in 99.8% of births.
In this study, the case is described of an umbilical metastasis as the presenting symptom of an ovarian adenosarcoma. The overall frequency of cutaneous metastases has been estimated at between 5 and 9%. Umbilical metastases are a rare occurrence: it is estimated that between 1 and 3% of patients with abdomino-pelvic disease present with an umbilical nodule. Epidemiological studies have shown the female predominance of this disease. The clinical characteristics of umbilical metastases cannot be visually distinguished from those of primary lesions. The clinical appearance is often that of a nodule of varying size, more or less painful, and sometimes ulcerated or suppurating as in the present case. The nodule may be indicative of cancer, or of cancer recurrence. The most frequently encountered histological type is adenocarcinoma (about 75% of cases), and is more rarely epidermoid, undifferentiated, or carcinoid. Etiological findings have indicated a digestive origin in over 55% of cases (stomach, colon, rectum, pancreas, in decreasing order of frequency), with a clear male predominance; cancers of gynecological origin are the second most frequent etiology, with ovarian cancers being the most common (34% of cases). Sister Mary Joseph nodule accounts for 60% of all malignant umbilical tumors (primary or secondary), and is usually associated with a poor prognosis (mean survival: 10-12 months). However, patient survival time could be lengthened by aggressive therapy, i.e., surgery combined with chemotherapy.
The possible existence of a beta(3)-adrenoceptor (beta(3)-AR) in human near-term myometrium was investigated by in vitro functional and biochemical studies and analysis of mRNA expression. SR 59119A and SR 59104A and CGP 12177 (two selective agonists and a partial agonist, respectively, of the beta(3)-AR), salbutamol and terbutaline (beta(2)-AR agonists) each produced a concentration-dependent relaxation of the myometrial spontaneous contractions. There were no differences in pD(2) values for the relaxing potencies of terbutaline, salbutamol, CGP 12177 and SR 59119A. The rank order for their relaxing efficacies was SR 59119A>SR 59104A>terbutaline approximately salbutamol approximately CGP 12177 (E(max)=52+/-7%, 42+/-12% and approximately 30% respectively). Propranolol, a beta(1)- and beta(2)-AR antagonist, and ICI 118551, a beta(2)-AR antagonist (both at 0.1 microM), did not affect the SR 59119A-induced relaxation whereas SR 59230A, a selective beta(3)-AR antagonist (1 microM), significantly reduced the maximal relaxing effect of SR 59119A. SR 59119A and salbutamol induced a significant increase in cyclic AMP levels that was antagonized by SR 59230A but not by propranolol for SR 59119A, and by propranolol but not by SR 59230A for salbutamol. The beta(3)-AR mRNA was positively expressed in myometrium preparations in a reverse transcription polymerase chain assay. The results presented provide the first evidence for the existence of the beta(3)-AR subtype in human near-term myometrium and suggest that the effects of SR 59119A might be mediated through an increase in cyclic AMP level.
BACKGROUND: Predicting postnatal renal function is crucial for the prenatal evaluation of fetal bilateral uropathies. Prenatal ultrasound can identify intrauterine terminal renal failure, but is not sensitive enough to identify those infants who would survive with an impaired renal function. Because it reflects fetal glomerular filtration, fetal serum beta2-microglobulin is a potential predictor of postnatal renal function. METHODS: Fetal serum beta2-microglobulin (beta2m) was assayed in 61 cases of bilateral or low obstructive uropathy, 74 controls, and 17 cases of bilateral renal agenesis, and was correlated with renal function. RESULTS: Fetal serum beta2m was 3.2 mg/L (range 1.5 to 4.7) in controls (N = 74), 9.5 mg/L (range 6.7 to 11.3) in bilateral renal agenesis (N = 17), 7 mg/L (5.1 to 10.6) in uropathy in which terminal renal failure resulted in termination of pregnancy (N = 26), and 3.7 mg/L (range 2.3 to 11.2) in live births with uropathy (N = 35). In the latter subgroup, fetal serum beta2m was significantly and positively correlated (r2 = 0.91) with postnatal serum creatinine. All survivors with a postnatal serum creatinine < or =50 micromol/L ha a fetal serum beta2m lower than 5 mg/L. Four of 6 survivors with a postnatal serum creatinine> 50 micromol/L had a fetal serum beta2m greater than 5 mg/L. CONCLUSION: Fetal serum beta2-microglobulin is a marker for renal function and predicts postnatal serum creatinine in bilateral or low fetal obstructive uropathy.
BACKGROUND/PURPOSE: Despite dramatic improvement in survival rate for neonates with gastroschisis, significant postoperative morbidity and a low mortality rate still occur. Furthermore, even in recent publications, some fetal death has been reported. Does this mean that antenatal diagnosis of gastroschisis is a missed opportunity? In fact, decreased amniotic fluid (AF) volume is observed in some fetuses with gastroschisis. However, oligohydramnios is associated with an increased risk of fetal suffering. When severe oligohydramnios is observed, intrapartum amnioinfusion, to restore AF volume, may help avoid fetal complications. METHODS: Two fetuses with gastroschisis and severe oligohydramnios were treated antenatally with amnioinfusion of saline solution. In one case, fetal heart beat decelerations were observed at 27 weeks' gestation among with the oligohydroamnios and serial transabdominal amnioinfusions were performed. In the second case, severe oligohydramnios was observed at 31, weeks and an amnioinfusion was performed. The 2 babies were delivered at 31 and 34 weeks, respectively. RESULTS: In both cases, exteriorized bowel was nearly normal at birth, and primary closure could be performed. Outcome was favorable, and they were discharged home on day 43 and day 54, respectively. CONCLUSIONS: Because fetuses with gastroschisis and oligohydramnios are part of a particular high-risk group, serial ultrasound examination and computerized fetal heart beat monitoring are necessary during the third trimester. In selected cases of gastroschisis associated with severe oligohydramnios, serial amnioinfusion may be required.