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Biomedical subjects

H Grandjean

Publications and source records attributed to H Grandjean.

At least 19 recordsLinked to original sources

Femur/foot length ratio for detection of Down syndrome: results of a multicenter prospective study. The Association Française pour le Dépistage et la Prévention des Handicaps de l'Enfant Study Group.

OBJECTIVE: The aim was to determine the sensitivity and specificity of a short femur for detection of trisomy 21 in the second trimester. STUDY DESIGN: Thirty-six investigators in 12 centers measured biparietal diameter and femur and foot lengths in 3582 14- to 24-week-old fetuses in mothers undergoing amniocentesis for age, history of genetic disorder, or laboratory signs. RESULTS: Among the various ratios for evaluating femur shortening the femur/foot ratio appeared to be the most discriminatory. At an upper cutoff level of 0.88 a sensitivity of 35% was obtained for 4.6% false positives in normal infants. However, to only obtain 2.3% false positives, the cutoff limit had to be set at 0.85, giving a sensitivity of no more than 15%. CONCLUSION: Determination of the femur/foot ratio improves ultrasonographic detection of trisomy 21 in the second trimester, although for systematic use it would lead to an unacceptable number of unnecessary amniocenteses.

Amniocentesis

Sonographic measurement of nuchal skinfold thickness for detection of Down syndrome in the second-trimester fetus: a multicenter prospective study. The AFDPHE Study Group. Association Française pour le Dépistage et la Prévention des Handicaps de l'Enfant.

OBJECTIVE: To determine the sensitivity and specificity of soft-tissue nuchal-fold measurement in the second-trimester fetus for the detection of trisomy 21. METHOD: Thirty-six investigators in 12 centers measured nuchal skinfold thickness in 3308 fetuses of 14-24 weeks' gestation. All mothers were referred for amniocentesis because of age, history of genetic disorder, or laboratory findings. Those referred with an ultrasound indication for amniocentesis, including nuchal-fold thickening, were excluded. RESULTS: Overall, nuchal skinfold was 6 mm or more in 8.5% of chromosomally normal fetuses and in 38% of those with trisomy 21. A false-positive rate below 5% was obtained by 81% of the investigators. Raising the cutoff of normality to 7 mm after 18 weeks' gestation improved specificity. CONCLUSION: Although the diagnostic value of this sign in skilled hands could allow its use as an indication for genetic amniocentesis at the second trimester, the method does not appear suitable for population screening because of the high variability in the results among the investigators.

Analysis of Variance

Did preterm deliveries continue to decrease in France in the 1980s?

To study the trends in gestational age and birthweight in France, we compared data from three surveys that were based on representative samples of births in 10 French regions and were conducted in 1972, 1981 and 1988-89. Only single livebirths were considered in the analysis. The rate of preterm births decreased from 7.9% in 1972 to 5.8% in 1981 and 4.0% in 1988-89. The corresponding rates of children with a birthweight below 2500 g were 5.4, 4.3 and 4.7%. The mean birthweight of preterm babies born in 1988-89 was lower than the mean birthweight of those born in 1972 and 1981. The reduction in preterm births cannot be attributed to the improved accuracy of gestational age determination, but the general use of ultrasound may have played a major role in the apparent reduction of the mean birthweight of preterm babies.

Birth Weight

[Short and mid-term outcome of a cohort of 1157 newborn infants with respiratory distress syndrome].

BACKGROUND: Data concerning neonates with acute respiratory distress syndrome (RDS) are still scarce. The characteristics and follow-up of a French cohort which has participated in an international trial concerning the efficacy of artificial surfactant have been studied. POPULATION AND METHODS: One thousand one hundred and fifty-seven neonates admitted from October 1990 to December 1991 in 27 French intensive care units because of RDS due to hyaline membrane disease were included in the study, whatever their birthweight and gestational age (GA). RESULTS: Three hundred and sixteen neonates (27.3%) were born from twin or multiple pregnancies. Fourty-five (5.5%) of the mothers had been given corticosteroids for the week preceding delivery. 55.5% were delivered by cesarean section. Mean GA was 31.0 +/- 2.9 weeks and mean birth-weight was 1,603 +/- 625 g. Two hundred and sixty-six neonates (23%) were small for GA. Two hundred and twenty-three died after a mean survival of 4.2 days (63% before the end of the first week and 80% before the end of the third week). Fifty percent of these deaths were due to respiratory distress, 28% to severe brain disorders and 9% to infections. The bronchopulmonary dysplasia rate was 21.7%. Early ultrasound scan of the brain showed major injuries in 19.5% of cases; the second scan performed in 822 infants was normal in 84.3%. CONCLUSIONS: Taking into account GA, mortality and morbidity rates were similar to those of the other non-French participating centres.

Birth Weight

Comparison between fluorescent peanut agglutinin lectin and GB24 antibody techniques for the assessment of acrosomal status.

In order to compare fluorescent peanut (Arachis hypogaea) agglutinin lectin and GB24 antibody (specific for the inner acrosomal membrane) techniques for the assessment of acrosome reaction, both methods were applied on semen specimens obtained from patients undergoing in-vitro fertilization (IVF). The acrosome status was evaluated after a 4 h incubation in B2 medium with and without calcium ionophore A23187. Results obtained with both techniques were compared and studied as a function of IVF outcome. The percentage of spontaneous acrosome-reacted spermatozoa was higher when assessed by lectin than by GB24 (19 +/- 2% versus 11 +/- 1%; P < 0.001). The difference between the two methods (lectins minus GB24) was significantly higher in abnormal than in normal spermatozoa (10 +/- 2% versus 4 +/- 2%; P < 0.05), but did not significantly correlate with the percentage of acrosomes with abnormal morphology (r = 0.28; NS). When studied in relation to the IVF results, the response to A23187 was higher in successes than in failures (45 +/- 2% versus 34 +/- 4%; P < 0.05) but there was no significant difference between methods. Thus the assessment of acrosome reaction is strongly influenced by the method used, particularly in abnormal spermatozoa. Since the results obtained with lectins were higher in abnormal spermatozoa, GB24 seems to be more effective for assessment of true acrosome reaction.

Acrosome

Placental transfer of glycosaminoglycans in the human perfused placental cotyledon model.

Placental transfer of unfractionated heparin (UH), of low molecular weight heparin CY 216 (LMWH) and of Dermatan sulphate (DS) was studied using the human perfused placental cotyledon model. Two different techniques were used to assess the transfer: labelled molecules and biological activities as measured by antifactor Xa or antifactor IIa activities. No biological activity was present in the fetal circulation, for any of the drugs used; however, very low fractions of the perfused radioactivity were recorded, 0.76% +/- 0.36%, 1.46% +/- 1.44% and 2.37% +/- 0.89% for DS, UH and LMWH, respectively.

Dermatan Sulfate

Maternal and umbilical cord concentrations of fentanyl after epidural analgesia for cesarean section.

The maternal and umbilical concentrations of fentanyl were measured after epidural analgesia for cesarean section, using a highly sensitive radioimmunoassay method. Sixteen parturients were anesthetized with a single epidural injection of a mixture of 85 mg bupivacaine 0.5%, 60 mg etidocaine 1%, and 100 micrograms fentanyl with epinephrine 1:200,000. Apparent maternal individual maximum peak concentration (Cmax) of fentanyl was 0.38 +/- 0.16 ng/ml (mean +/- SD) (range 0.12-0.59 ng/ml) and the time to reach Cmax (Tmax) was 24 +/- 14 min (range 5-60 min). Infants were born 19 to 42 min after epidural administration of fentanyl (mean 27 min). Fentanyl concentrations in neonates was 0.13 +/- 0.04 ng/ml for the umbilical vein and 0.06 +/- 0.03 ng/ml for the artery. The fetus extraction ratio was 53 +/- 19% (range 20-83%). The large difference between arterial and venous concentrations of fentanyl may be due to a metabolization by the fetus and/or an uptake of the drug in the fetal tissues. Thus, even if fentanyl levels reaching the fetus after cesarean section under epidural anesthesia, using local anesthetics with 100 micrograms of fentanyl, are within safe range values, the likelihood of fentanyl uptake by fetal tissues calls for a cautious use of repeated fentanyl administration.

Analgesia, Epidural

The effect of oxytocin on oestradiol-17 beta and testosterone secretion by cultured human granulosa cells.

The effect of oxytocin at different concentrations was tested on the secretion of oestradiol-17 beta and testosterone by cultured human granulosa cells obtained by follicular punctures during in-vitro fertilization (IVF) attempts. Oxytocin had no effect on testosterone secretion, either in the absence or the presence of follicle stimulating hormone (FSH). It had no effect on oestradiol-17 beta in the absence of FSH. However, it decreased the FSH-stimulated secretion of oestradiol-17 beta in a certain number of cases. This inhibitory effect appears to be associated with cells more responsive to FSH and was identified in women found to be successful in achieving pregnancy during IVF attempts.

Androstenedione

Enhancement of ricin A chain immunotoxin activity by perhexiline on established and fresh leukemic cells.

In the perspective of increasing the clinical potential of ricin A chain immunotoxins (RTA-ITs), perhexiline (Pex) and four structural analogues (Pex 2, Pex 3, Pex 7, and Pex 11) were evaluated for their ability to enhance RTA-IT activity in vitro. Only perhexiline significantly enhanced the cytotoxic activity of anti-CD5 RTA-ITs, T101 and T101-F(ab')2, on CEM III cell line (30- to 2000-fold), and of anti-HLA-DR RTA-IT, HNC-241, on both RAJI cell line (greater than 100-fold) and two immortalized cell lines originating from patients suffering from B-cell chronic lymphocytic leukemia, EHEB and FS2 D5 (10-fold). On 16 consecutive fresh B-cell chronic lymphocytic leukemia cell samples, significant T101-F(ab')2 RTA-IT and HNC-241 RTA-IT enhancement was observed with perhexiline which was comparable to that of NH4Cl and monensin. Perhexiline almost completely blocked RTA-IT intracellular degradation and profoundly modified its routing. These observations were linked to perhexiline-induced lipidosis via inhibition of sphingomyelinase activity. In conclusion, since the concentrations used are relevant with the pharmacokinetics of this agent, perhexiline appears to be a promising agent for in vivo enhancement of ricin A chain immunotoxins.

Ammonium Chloride

Influence of pregnancy on human immunodeficiency virus disease.

Over a period of 3 years (mean 16, extremes 3 and 36 months), we compared clinical and laboratory parameters of 128 female, human immunodeficiency virus (HIV)-infected patients, all in clinical stage II or III (CDC classification). 34 patients were pregnant and delivered a viable infant after at least 28 weeks of amenorrhea (group I), 29 patients were pregnant and had a spontaneous or induced abortion during the first or second trimester (group II), and 64 were non-pregnant female control patients (group III). The changes in the clinical stages over time were not statistically significant between the groups. The only laboratory parameters that were significantly higher in group I at the time of the delivery were: leucocyte count (p less than 0.001), lymphocyte count (p less than 0.05), and sedimentation rate (p less than 0.001). These changes are known to be related to pregnancy and not to HIV disease. All other laboratory parameters showed no significant differences within and between the groups. We conclude, that pregnancy--carried to term or interrupted--does not aggravate the natural evolution of HIV infection in clinical stage II and III patients.

Adolescent

Effects of pH on antipyrine transfer across the human placenta ex vivo.

The influence of pH variations on transplacental transfer of antipyrine was studied using a human placental cotyledon perfused ex vivo. The antipyrine transfer rate is positively correlated with the pH in the fetal circulation and negatively correlated with the pH in the maternal circulation. Thus, the transfer rate is negatively correlated with the difference between pH values in maternal and fetal circulations. The antipyrine transfer rate is also positively correlated with the flows in maternal and fetal circulations. The above parameters allowed to explain 50% of the variance on the transfer rates obtained in various experimental conditions. In a final series of experiments where these parameters for each placenta were fixed at identical values, a good reproducibility in the results was obtained, the variation coefficient being 17%. Thus, establishing the effect of variations in pH allowed a good standardization of the perfused cotyledon model. This effect cannot be explained by modifications in the ionized fraction of the antipyrine molecular and is probably due to physiological mechanisms.

Adult

Sensitivity of fresh leukemic cells to T101 ricin A-chain immunotoxin: a comparative study between Fab fragment and whole Ig conjugates.

We compared the cell killing potency of a whole Ig ricin A-chain immunotoxin (T101 IgG-RTA) against its Fab fragment counterpart (T101 Fab-RTA) on both CEM cells and fresh malignant lymphoid cells. A dye exclusion assay (DEA), was used to evaluate the kinetics of leukaemia cell viability mediated in vitro by each immunotoxin (IT). This study found that in the absence of ammonium chloride (NH4Cl), used as an enhancer agent, T101 Fab-RTA was significantly more toxic to both CEM and fresh leukaemia cells than T101 IgG-RTA. In the presence of NH4Cl (10(-2) M), while no differences could be found between the two IT on CEM cells, T101 Fab-RTA was clearly superior to T101 IgG-RTA on fresh leukaemia cells. These results suggest that T101 Fab-RTA may offer an excellent alternative to T101 IgG-RTA for IT treatment of CD5 positive leukaemia patients.

Ammonium Chloride

Increased levels of serum follicle-stimulating hormone and luteinizing hormone associated with intrinsic testicular hyperthermia in oligospermic infertile men.

A Negative correlation between spermatozoa output and serum gonadotropin levels, as well as between scrotal temperature and spermatozoa output, has been found in man. However, no studies have been done on the relationship between scrotal temperature and serum gonadotropin levels. This paper reports such data from 212 infertile men. The upper limit for normal scrotal temperature was defined as the 90th percentile value (35.3 C) of a control group of 64 fertile men whose mean serum FSH and LH levels were 6.0 +/- 0.8 (+/- SE) and 6.4 +/- 0.7 IU/L, respectively. This value for scrotal temperature (35.3 C) was used to classify infertile men into 3 groups: bilateral hyperthermia (n = 56), unilateral hyperthermia (n = 40), and bilateral normothermia (n = 116). In the unilateral and bilateral hyperthermic groups serum LH and FSH levels were significantly increased compared with those in the normothermic group. The mean serum testosterone values were similar in all groups. To study the relationships between serum gonadotropin levels or spermatozoa output and scrotal temperature, the infertile men also were divided into classes according to their spermatozoa output. These classes were subdivided into two groups, normothermic or hyperthermic, according to whether the left scrotal temperature was equal to or less than, or more than 35.3 C. For the infertile men whose spermatozoa output was more than 60 X 10(6) spermatozoa/ejaculate (normospermia), there was no significant difference between the serum gonadotropin levels of the normothermic (n = 42) and the hyperthermic (n = 20) groups. Among the oligospermic men (spermatozoa output, 0.1-60 X 10(6) spermatozoa/ejaculate), the hyperthermic group (n = 65) had significantly higher serum gonadotropin levels and significantly smaller testicular volumes than the normothermic group (n = 71). The two oligospermic groups also had significantly higher serum FSH values than the infertile normospermic groups. These results were not linked to the presence of a varicocele or a history of cryptorchidism, as the prevalence of varicocele and cryptorchidism was equally distributed within the groups studied. We conclude that the increase in serum gonadotropin levels in the case of a decrease in spermatozoa output is significantly greater in the presence of associated scrotal hyperthermia.

Adult