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The Robertson–Stiff fluid (RS) is a yield-pseudo-plastic model which has been used to describe the rheological properties of drilling fluids, cement slurries and bentonite suspensions. Experimentally, several rheological data showed that this model provides more consistently accurate descriptions of the rheology of such fluids than other viscoplastic models. This result motivates us to study theoretically the peristaltic transport for this shear-thinning model and for other viscoplastic models in the presence of heat and mass transfer in a cylindrical tube. For long wavelength and low Reynolds number approximations, an analytical solution is obtained. The results showed that the velocity and the temperature decrease with increasing the yield parameter and the power index while they increase with the increase in the occlusion parameter. We also observed an opposite behavior of the concentration versus these physical parameters. Moreover, all these parameters enhance the mechanical efficiency of pumping. In addition, the comparison shows that the velocity, temperature and the absolute value of concentration are greater for the proposed model than those of Herschel–Bulkley, Bingham and Casson models, respectively.

L’alimentation mediterraneenne est un terme utilise pour decrire les habitudes alimentaires traditionnelles de populations du pourtour mediterraneen. Cette alimentation englobe un tres grand nombre de pratiques culinaires differentes selon les pays et selon les populations qui ne partagent pas forcement les memes modes de vie, cultures et religions. Mais ces pratiques culinaires si differentes presentent certaines caracteristiques communes qui les rapprochent. Notons, par exemple, une forte consommation de legumes et de fruits varies, de cereales, de legumineuses, l’emploi de l’huile d’olive comme source principale de matieres grasses, une faible consommation de lait et de beurre, une consommation moderee de vin rouge au cours des repas et l’utilisation d’herbes et d’aromates. Les autres points communs sont la recherche de plaisirs sensoriels et l’importance accordee aux repas et aux valeurs immaterielles (sociabilite, partage, hospitalite, convivialite, etc.). Cet article traitera de la diversite, de l’historique du concept de la diete mediterraneenne et de l’evolution de l’alimentation dans le pourtour mediterraneen.

Ovarian monitoring requires the determination of serum estradiol and progesterone levels. We investigated whole follicular steroidogenesis under rFSH in medically assisted procreation (MAP: 26 IVF, 24 ICSI) compared to 11 controls (IUI). Estrone, estradiol, Δ4-androstenedione, testosterone, progesterone and 17-hydroxyprogesterone were measured by immunoassay and mass spectrometry except for estrogens. At the start of a spontaneous or induced cycle, steroids levels fluctuated within normal ranges: estradiol (314–585 pmol/L), estrone (165–379 pmol/L) testosterone (1.3–1.6 nmol/L), Δ4-androstenedione (4.5–5.6 nmol/L), 17-hydroxyprogesterone (2.1–2.2 nmol/L) and progesterone (1.8–1.9 nmol/L). 17-hydroxyprogesterone, Δ 4-androstenedione and estradiol predominated. Then estradiol and oestrone levels rise, but less markedly for oestrone in IUI. In MAP, rFSH injections induce a sharp increase in estrogens associated with a rise in 17-hydroxyprogesterone and Δ4-androstenedione levels, disrupting oestrogen/androgen ratios. rFSH stimulation induces an ovarian hyperplasia and Δ4pathway which could become abnormal. Determining 17-hydroxyprogesterone and Δ4-androstenedione levels with LC-MS/MS may therefore be useful in managing recurrent MAP failures.

In the field of heat transfer, the use of the properties of rheological behavior inherent to suspensions of nanoparticles in heat transfer fluids has been the subject of several years of work. Our study concerns the particular case of suspensions of multilayered carbon nanotubes (MNTCs) in glycerol. We highlight the effect of the mass fraction φ of (MNTCs) on the rheology of the solutions for 0.1% ≤ φ ≤1%, on the temperature [30-80°C] and the effect on a heat exchanger. The experimental results obtained are described by viscoplastic models for which the yield stress increases with φ. We then propose a law of polynomial evolution of the apparent viscosity as a function of the volume fraction for each value of the shear rate varying from 0s-1 to 100s-1.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 42 - N° 8 - p. 752-759

Summary: The effect of long term treatment with D-Trp6-LH-RH in microcapsules (GnRH-A) on pituitary gonadal axis was studied in a adolescent and adult Fox-terrier dogs. They received intramuscularly 50 μg/ GnRH-A/kg, on days 1 and 21 and every 4 weeks thereafter. Three adult dogs received 4 injections. cLH, cFSH and T levels were undetectable on day 7. Detectable then normal levels occurred 60 and 90 days respectively after the last injection on day 77. Testis thickness was respectively 22.1±0.8 mm and 16.3±0.8 mm on days 0 and 77; initial values were observed 90 days later. Spermatozoa disappeared from the ejaculate on day 21 in 2 dogs; reappearance and complete recovery were observed on days 161–175 and 252 respectively. Histological findings showed on day 91 atrophic lesions of testis and prostate and spermatogonia were present in all seminiferous tubules. After recovery a normal histological appearance was noticed. Three adolescent 29 weeks old dogs received 14 injections, the last one on day 357. cLH, cFSH and T levels were undetectable only from day 105. Testis thickness were respectively 15.8±0.7 mm, 18.1±0.7 mm, 12.5±0.3 mm and 21.4±0.7 mm on days 0, 21, 357 and 490. Initially, no spermatozoa were present in the ejaculates, they appeared in 2 dogs after 2 months for 20 to 40 days then disappeared until day 449. Normal semen caracteristics were observed in all three dogs on day 581. Histological findings on day 371 were comparable to those observed in the adult dogs. This study demonstrates that longterm treatment with D-Trp6-LH-RH in microcapsules leads to a reversible inhibition of spermatogenesis in dogs. The delayed response in adolescent dogs might be due to a transient resistance to therapy related to. Zusammenfassung: In einer experimentellen Studie wird an heranwachsenden und erwachsenen Fox-Terriern der Einflus einer Langzeit-Therapie mit D-Trp6-LH-RH in Mikrokapselform (GnRH-A) auf die Hypophysen-Gonaden-Achse untersucht. Die Tiere erhielten am 1. und 21. Tag, sowie alle 4 Wochen spater jeweils 50 μg/GnRH-A/kg i.m. Drei erwachsene Hunde erhielten 4 Injektionen. cLH, cFSH und Testosteron waren am 7. Tag nicht zu bestimmen. Die Normalwerte waren dagegen bestimmbar nach 60 bzw. 90 Tagen, wenn die letzte Inj. am 77. Tage gegeben war. Die Hodendicke betrug 22, 1±0,8 mm und 16.3± 0,8 mm an den Tagen 0 und 77; die Anfangswerte wurden 90 Tage spater bestimmt. Die Spermatozoen verschwanden am 21. Tag aus den Ejakulat bei 2 Hunden; sie kehrten zuruck an den Tagen 161–175 und 252. Die histologischen Befunde zeigten am 91. Tage eine Atrophie des Hodens und der Prostata, die Spermatogonien waren uberall nachweisbar. Nach einer Erholungsphase waren normale histologische Verhaltnisse gegeben. Drei heranwachsende Hunde im Alter von 29 Wochen erhielten 14 Injektionen, die letzte Inj. am 357. Tag. cLH, cFSH und Testosteron waren nicht zu bestimmen mit Ausnahme des 105. Tages. Die Hodendicke betrug 15,8±0,7 mm, 18.1±0,7 mm, 12,5±0,3 mm und 21,4±0,7 mm an dem Tage 0, 21, 357 und 490. Anfangs waren keine Spermatozoen im Ejakulat nachzuweisen; bei zwei Tieren erschienen sie nach 2 Monaten fur 20–40 Tage und verschwanden dann wieder bis zum 449. Tag. Die normalen Spermacharakteristika wurden bei allen drei Hunden am 581. Tage beobachtet. Die hostologischen Resultate waren am 371. Tage mit denen zu vergleichen, die bei erwachsenen Hunden erhoben waren. Diese Untersuchung belegt, das eine Langzeitbehandlung mit D-Trp6-LH-RH in Mikrokapselform zu einer reversiblen Hemmung der Spermatogenese bei Hunden fuhrt. Die verzogerte Reaktion bei heranwachsenden Hunden durfte auf eine vorubergehende Resistenz gegenuber der Therapie zuruckgehen.

Transvaginal pelvic ultrasound is the first-line imaging examination for presumed benign ovarian tumors (PBOT) in adult women (Grade A). Ultrasound is sufficient for characterizing a unilocular anechoic cyst smaller than 7cm (Grade A). Magnetic resonance imaging is the recommended second-line investigation for indeterminate masses or masses larger than 7cm (Grade B). Serum CA-125 assay is not recommended for first-line diagnosis in adult women (Grade C). In women with a unilocular anechoic cyst, hormone therapy is ineffective and not recommended (Grade A). Ultrasound-guided aspiration is not recommended (Grade B). Abstention is an option in adult women with a unilocular asymptomatic anechoic cyst smaller than 10cm and no history of cancer (Grade B). If symptoms develop, laparoscopy is the gold standard for surgical treatment of PBOT (Grade A). Conservative surgical treatment (cystectomy) should be preferred to oophorectomy in pre-menopausal women without a previous history of cancer (Grade C). In cases of suspected adnexal torsion, laparoscopic surgical exploration is recommended (Grade B). Conservative treatment or detorsion without oophorectomy is recommended for pre-menopausal women regardless of the estimated torsion duration and macroscopic appearance of the ovary (Grade B). During pregnancy, expectant management is recommended for unilocular asymptomatic anechoic cysts smaller than 6cm (Grade C).

An experiment was conducted to examine whether increased CLA in milk of dairy cows fed fresh pasture compared with alfalfa and corn silages was because of ruminal or endogenous synthesis. Eight Holsteins were fed a total mixed ration using alfalfa and corn silages as the forage source in confinement or grazed in a replicated crossover design. The proportion of total fatty acids as CLA (primarily c9, t11-18:2) in g/100 g was 0.44 v. 0.28 in ruminal digesta, 0.89 v. 0.53 in omasal digesta and 0.71 v. 1.06 in milk during confinement feeding and grazing, respectively. Blood plasma CLA was 0.54 v. 1.05 mg/l for the two treatments, respectively. The increased concentration of CLA in milk with grazing likely resulted from increased synthesis through desaturation of t11-18:1 in the mammary gland.

Cancer Antigen 125 (CA125) and Human Epididymis Protein 4 (HE4) are the most studied ovarian tumor markers. Their diagnostic performance for identification of ovarian cancer are superior to CA19-9, CA72-4, and carcinoembryonic antigen, which are no more recommended for the diagnosis of presumed benign ovarian tumor. HE4 (140 pmol/L) is superior to CA125 (30 U/mL) in terms of specificity and positive likelihood ratio. CA125 and HE4 can be combined into an algorithm ROMA, or associated to clinical information (composite index), biological data (OVA1) or imaging (Risk for Malignancy Index (RMI), LR2). ROMA algorithm is an exponential equation combining plasmatic concentrations of HE4 and CA125. ROMA is more sensitive and less specific than HE4 in predicting epithelial ovarian cancer. ROMA is more accurate in post-menopausal women. The performance of ROMA is lower than the ultrasound model LR2 in differentiating malignant from benign ovarian tumors, whatever the hormonal status. The composite index combining CA125 with a symptoms index (pain, abdominal distension, bloating, difficulty eating) has a good sensitivity in a screening program, but because of a 12% false positive rate, ultrasound is required before management. The RMI algorithm is based on serum CA125, ultrasound findings (septation, solid zones, metastases, ascite, bilaterality) and menopausal status. RMI is less sensitive, but more specific than ROMA or OVA1 for the classification of ovarian masses. The addition of HE4 to RMI seems to be the most accurate. The subjective evaluation of ovarian cysts by sonography and color Doppler is better than ROMA and RMI algorithms, and not affected by the hormonal status.

Treatment with small doses of subcutaneous insulin is being investigated as a possible approach to prevent type 1 diabetes in humans. The mechanism of prophylactic insulin therapy could involve the inhibition of beta-cell secretory activity and/or the initiation of an active immunoregulatory process. To evaluate the pure metabolic effect of exogenous insulin, the present study assessed whether daily subcutaneous administration of ultralente insulin alters beta-cell function in normal adults. Fourteen healthy adults were randomized to receive 0.2 U/kg x d ultralente insulin (Ultratard; Novo Nordisk, Bagsvaerd, Denmark) or placebo subcutaneously once daily for 30 days. Plasma glucose, C-peptide, and insulin concentrations were measured in the fasting state and 1 hour after a standardized breakfast, during treatment and during a recovery period of 10 days. Insulin administration induced a 15% to 40% decrease of fasting plasma C-peptide. In contrast, postbreakfast plasma C-peptide increased by 40% to 90% in subjects receiving insulin. Fasting and postbreakfast C-peptide concentrations were significantly different between groups during the injection period after adjustment for baseline concentrations (P < .05, ANOVA with repeated measures). These alterations disappeared 3 days after cessation of insulin treatment. The present regimen of exogenous insulin alters endogenous insulin secretion in normal subjects. Instead of the expected beta-cell rest, the effect appeared to be dual, with insulin secretion decreasing in the basal state and increasing after meals.

The quinoline-3-carboxamide, linomide, protects non-obese diabetic mice from diabetes. The effects of linomide on insulin needs and beta cell function were studied in recent juvenile Type I diabetes in a double-blind trial. Patients with recent onset diabetes were randomly assigned to treatment with a fixed dose of 2.5 mg linomide (42 patients) or placebo (21 patients) for 1 year, in addition to insulin and diet. Glycated haemoglobin was 10–15 % lower at 9 months (p = 0.003) and 12 months (p < 0.05) in the linomide group. The insulin dose was 32–40 % smaller in the linomide group at 3 (p < 0.03), 6 (p < 0.02), 9 (p < 0.001) and 12 months (p = 0.01). Insulin doses correlated negatively with C peptide values (p = 0.001–0.002). The trend for higher C peptide values in the linomide group did not reach significance. In a post hoc subgroup analysis performed in 40 patients (25 from the linomide group and 15 from the placebo group) who still had detectable residual beta cell function at entry, linomide was associated with 45–59 % higher C peptide value at 6 months (p < 0.05), 9 months (p < 0.05) and 12 months (p < 0.05). The main adverse effects of linomide were mild transitory anaemia (45 vs 10 % in the linomide and placebo groups), thrombocytopenia (24 vs 10 %), and mild joint discomfort (45 vs 5 %) with no clinical signs. In conclusion, low-dose linomide reduced the insulin needs in patients with juvenile Type I diabetes of recent onset and improved beta cell function in patients who still had detectable beta cell function at entry. These results support further clinical and experimental studies to define the effects of linomide in Type I diabetes provided the safety of linomide is reliably established. [Diabetologia (1998) 41: 1040–1046]

Objectif Le syndrome de Turner (ST) est caracterise par l’absence de la totalite ou d’une partie d’un chromosome X. Son incidence est de 1/2500 naissances de sujets a phenotype feminin, 50 % sont des monosomies X, 25 % des mosaiques, les autres des duplications ou deletions partielles. La folliculogenese ovarienne est absente ou tres faible, mais une puberte spontanee est parfois possible. L’AMH serique est un marqueur fiable de la presence de follicules et notre but a ete de comparer l’efficacite de deux dosages, classique et ultrasensible (pico-AMH). Materiel et methodes Chez 39 patientes (11–25 ans), sous-ensemble d’une vaste etude sur la cryoconservation ovarienne, sept monosomies X0 (GI), 12 mosaiques X0/XX (GII), 20 autres mosaiques (GIII) ont ete dosees par les reactifs AnshLabs : inhibineB (limite de detection LD 10 ng/mL), AMH (LD 0,15 pmol/L) et pico-AMH (LD 0,028 pmol/L). Resultats Comme attendu, inhibineB et AMH sont indetectables en GI (sauf 1 cas) mais pico-AMH est detectable dans 4/7 cas. En GII, l’inhibibineB est indetectable dans 6/12 cas, AMH dans 5, et pico-AMH dans 3 seulement. En GIII, l’inhibineB est indetectable dans 13/20, AMH dans 11 cas et pico-AMH dans 9 cas seulement. Conclusion Chez les sujets turneriens âges de 11 ans ou plus, le nouveau dosage ultrasensible de l’AMH detecte une activite secretoire folliculaire dans un nombre de cas superieur au dosage classique : 24 vs 17. La confrontation a l’histologie demontre que les valeurs observees sont bien correlees, comme espere, au nombre de follicules etabli par biopsie.

Micropenis is defined as a stretched penile length of less than 2-2.5SD for age. Aetiologies include hypogonadotropic hypogonadism, testicular dysgenesis, defects in testosterone synthesis, androgen resistance [5α-reductase (5αR) deficiency or partial androgen insensitivity] and other rare causes like growth hormone GH deficiency. Often, the cause remains unknown. The aim of this study was to determine whether isolated micropenis with normal plasma testosterone could hide a molecular defect in the androgen pathway. Twenty-six boys with isolated micropenis were included in this study. All of them had 46,XY karyotype, normal luteinizing hormone and follicle-stimulating hormone and a normal plasma testosterone response to human chorionic gonadotropin testing. Androgen receptor (AR), 5αR and steroidogenic factor 1 (SF1) genes were sequenced. A mutation in the AR gene was found in two patients, and a new mutation in the SF1 gene was found in one patient who was the only one to have a low level of inhibin B (InhB). This is the first report of isolated micropenis as a revealing symptom of AR and SF1 mutations. Anti-Mullerian hormone and InhB should thus be evaluated in patients with isolated micropenis, even when plasma testosterone is in the normal range. Detection of gene mutations is helpful for diagnosis, treatment and genetic counselling for probands.

Inhibins, activins, and anti-Mullerian hormone (AMH) are gonadal dimeric peptides produced in ovaries and testes by homologous cells, granulosa cells and Sertoli cells, respectively. The production of inhibins is driven by FSH, that of AMH may indirectly depends on FSH, while it is down regulated, at least in the male, by testosterone. In the past decade, measurements of serum inhibin and AMH have provided useful tools for clinical investigation in gonadal disorders: pseudohermaphroditism, androgen insensitivity, anorchidism, gonadal dysgenesis, disorders of pubertal developpement. Inhibins, activins, and AMH are also reliable markers of gonadal tumors. They are extensively used as indexes of fertility: in the male the production of inhibin B reflects the spermatogenetic activity, in women both inhibin B and AMH levels are correlated with the number of preantral and early antral follicles and reflect the ovarian reserve of follicles available for recruitment.

The neonatal-midinfancy surge in pulsatile gonadotropin secretion is attributable to an increase in GnRH pulse amplitude and is associated with a rapid expansion of Leydig and Sertoli cell populations with concomitant surges in testosterone, inhibin, and anti-Mullerian hormone production as well as an increase in testicular volume. Boys with congenital hypogonadotropic hypogonadism (HH) do not activate these processes. A potential cause for azoospermia and infertility in adult life is deficient proliferation of immature Sertoli cells before and during puberty due to the absence of FSH.The objective of the study was to investigate whether early postnatal continuous sc infusion of gonadotropins could mimic the physiological growth of testes and to evaluate responses of the Leydig and Sertoli cells to early gonadotropin replacement.Two neonates (P1 with hypotuitarism and P2 with HH) with micropenis and microorchidism were treated for 6 months with high doses of recombinant LH and FSH (a gift of Luveris and Gonal-F from Serono, Lyon, France) delivered sc with an insulin pump.Gonadotropin continuous sc infusion increased mean serum LH and FSH to normal or supranormal levels. Mean testosterone increased from undetectable levels to 7.6 and 5.2 nmol/liter, respectively, in P1 and P2. Inhibin B and anti-Müllerian hormone increased to normal levels. Mean testicular volume increased from 0.45 to 0.57 ml at birth to 2.10 ml at 7 months. Stretched penile length increased from 8 to 30 mm (P1) and 12 to 48 mm (P2).The present regimen induced physiological postnatal testes growth and high-normal activation of Leydig and Sertoli cells.

BACKGROUND: In normo-ovulatory infertile women undergoing mild ovarian stimulation out of IVF, FSH stimulation regimen must be carefully adjusted to control the number of recruited follicles and to prevent multiple pregnancies. The aim of this prospective study was to assess the effect of the timing of FSH administration (fixed dose and duration) on the number of large follicles. METHODS: Women were prospectively randomized by means of sealed envelopes to receive daily 112.5 IU recombinant FSH (rFSH), either from cycle day (CD) 2-6 (Group A) or from CD 7-11 (Group B). Hormonal measurements and follicular ultrasound assessments were performed on CD 2, 7 and 12. RESULTS: On CD 12, the development rate of exactly two follicles >or=14 mm in diameter was significantly lower in Group A than in Group B (4% of women versus 42%, P = 0.002). Although the pattern of serum estradiol (E(2)) concentrations in Group A displayed a plateau from CD 7, the cancellation rate for overstimulation (more than three follicles >or=14 mm in diameter) was significantly increased (P = 0.009). CONCLUSIONS: Preventing the closure of the FSH window by mid to late follicular phase FSH administration better fulfils the objective of obtaining a limited number of large follicles than surpassing the FSH threshold by an early administration.

To investigate the frequency of macrosomia in an homogeneous cohort of type 1 diabetic mothers and to analyze the influence of maternal factors and glycemic control on the incidence of fetal macrosomia.Fifty-five consecutive type 1 diabetic first-pregnancies were prospectively studied. Macrosomia was defined by a ponderal index above the 90(th) percentile. Venous cord blood levels of insulin, C peptide and leptin were measured at delivery. The influence of HbA1c levels and other maternal variables on the occurrence of macrosomia and on the ponderal index was assessed using a stepwise regression logistic model.The mean (+/- SD) birth weight was 3482 (+/- 497) g at 37.4 +/- 1.0 weeks gestation. Macrosomia occurred in 29 cases (53.7%). Fetal insulin, C peptide and leptin levels were significantly higher in macrosomic than in non macrosomic infants. Maternal age, duration of diabetes, pregravid body mass index, parity, weight gain during pregnancy, presence of a microangiopathy, nephropathy, smoking habits, gestational hypertension or preeclampsia, and HbA1c levels throughout pregnancy did not differed between mothers of macrosomic and non macrosomic infants. In the stepwise analysis none of these covariates was explanatory of the ponderal index.The frequency of macrosomia remains very high in infants of type 1 diabetic mothers despite a reasonable degree of glycemic control. The variability of the fetal growth response to mild hyperglycemia prompts for the identification of other factors involved in the modulation of fetal growth.

We describe a woman with complete hypogonadotropic hypogonadism and a new compound heterozygous mutation of the GnRH receptor (GnRHR) gene. A null mutation L314X leading to a partial deletion of the seventh transmembrane domain of the GnRHR is associated with a Q106R mutation previously described. L314X mutant receptor shows neither measurable binding nor inositol phosphate production when transfected in CHO-K1 cells compared to the wild-type receptor. The disease is transmitted as an autosomal recessive trait, as shown by pedigree analysis. Heterozygous patients with GnRHR mutations had normal pubertal development and fertility. The present study shows an absence of LH and FSH response to pulsatile GnRH administration (20 microg/pulse, sc, every 90 min). However, GnRH triggered free alpha-subunit (FAS) pulses of small amplitude, demonstrating partial resistance to pharmacological doses of GnRH. FSH, LH, and FAS concentrations were evaluated under chronic estrogen treatment and repeat administration of GnRH. Not only were plasma FSH, LH, and FAS concentrations decreased, but FAS responsiveness was reduced. This new case emphasizes the implication of the GnRH receptor mutations in the etiology of idiopathic hypogonadotropic hypogonadism. We also have evidence for a direct negative estrogen effect on gonadotropin secretion at the pituitary level, dependent on the GnRHR signaling pathway.

Oral administration of autoantigens can slow the progression of beta-cell destruction in non-obese diabetic mice. We investigated whether oral administration of recombinant human insulin could protect residual beta-cell function in recent-onset type 1 diabetes.We enrolled 131 autoantibody-positive diabetic patients aged 7-40 years within 2 weeks of diagnosis (no ketoacidosis at diagnosis, weight loss10%, polyuria for6 weeks). They were randomly assigned 2.5 mg or 7.5 mg oral insulin daily or placebo for 1 year, in addition to subcutaneous insulin therapy. Serum C-peptide concentrations were measured in the fasting state and after stimulation, to assess beta-cell function. Autoantibodies to beta-cell antigens were assayed. Analyses were by intention to treat.Baseline C-peptide and haemoglobin A1c concentrations were similar in the three groups. During follow-up, there were no differences between the groups assigned 2.5 mg or 7.5 mg oral insulin or placebo in subcutaneous insulin requirements, haemoglobin A1c concentrations, or measurements of fasting (mean at 12 months 0.18 [SD 0.17], 0.17 [0.17], and 0.17 [0.12] nmol/L) or stimulated C-peptide concentrations (glucagon-stimulated 0.39 [0.38], 0.37 [0.39], and 0.33 [0.24] nmol/L; meal-stimulated 0.72 [0.60], 0.49 [0.49], and 0.57 [0.51 nmol/L]. Neither age nor C-peptide concentration at entry influenced treatment effects. No differences were seen in the time-course or titres of antibodies to insulin, glutamic acid decarboxylase, or islet antigen 2.At the doses used in this trial, oral administration of insulin initiated at clinical onset of type 1 diabetes did not prevent the deterioration of beta-cell function.

Since 1981, GnRH agonist administration has been the treatment of choice for central precocious puberty. Continuous administration of the agonist, instead of permanently stimulating gonadotropin secretion, deeply suppresses LH and FSH levels and induces a marked inhibition of gonadal activity and regression of clinical symptoms. This inhibitory effect is due both to specific kinetic parameters relative to natural GnRH, and to marked alterations of the biosynthetic pathways of gonadotropin subunits. The half disappearance time of infused agonists is 3-10 fold that of natural GnRH. This means that the residence time of GnRH agonists is significantly longer than that of GnRH. The resistance of agonist to enzymatic degradation, mainly due to the substitution of a hydrophobic D-amino acid for glycine 6, is one of the factors involved in the increased availability of GnRH superagonists. The paradoxical effects of GnRH superagonists are still incompletely understood. In children long-term treated with depot formulations of triptorelin or leuprorelin, alpha-subunit secretion is markedly increased, and remains sensitive to exogenous GnRH, which demonstrates that the gonadotrophs are not totally desensitized. Despite the sustained stimulation of a-subunit secretion, no deleterious side effects, either during therapy or during post-therapy follow-up, have been reported in children treated with GnRH agonists. It should be noted that alpha-subunit responsiveness to exogenous GnRH decreases progressively after several years of treatment, although it is never completely abolished. On the other hand, LH beta-subunit secretion is suppressed as evidenced by radioimmunoassay of LH beta-subunit in serum chromatographic fractions from children treated with triptorelin. This differential pattern of secretion parallels that of mRNA levels in rat pituitary after in vivo exposure to triptorelin. Both pharmacodynamic and pharmacokinetic data can help diagnose the situations of resistance or escape. The lack of clinical effect of GnRH in the treatment of precocious puberty can be due to true resistance, or to an inappropriate injection schedule, or to abnormal metabolism. Measurement of serum alpha-subunit level, and, if needed, of serum agonist level, generally provides the answer.

The impact of treatment of central precocious puberty (CPP) with GnRH agonists on final statural height (FH) remains controversial, and guidelines on the optimal time point for interruption of these treatments have not been established. We analyzed the long term results of 58 girls and 8 boys uniformly treated with triptorelin slow release formulation (Decapeptyl, triptorelin-SR) for CPP and compared their FH with predicted height before treatment and with the FH of a historical group of patients not treated with GnRH agonist. The FH SD score was close to 0 and was not different from the genetic target height. In girls, FH was improved by 4.8 +/- 5.8 cm compared with predicted height before treatment and by 8.3 cm by comparison with a historical group. In boys, comparison with a historical group revealed a 13.7-cm improvement, whereas predicted height before treatment was similar to FH. Three variables were independently associated with FH in girls: the bone age/statural age ratio at the onset of treatment (negatively), the height SD score at the end of treatment, and the posttreatment growth spurt (delta FH - height at the end of treatment). The influence of the posttreatment growth spurt, itself dependent on age and bone age at the interruption of treatment, suggests that continuing treatment beyond the age of 11 yr in girls does not improve and could actually decrease FH. This point should be evaluated in a formal controlled trial.

Given the central role of the GnRH receptor (GnRHR) in the regulation of the gonadotrophin secretion, it might be implicated directly or indirectly in the pathogenesis of gonadotroph tumours.We determined if GnRHR mRNA was expressed in gonadotroph tumours using RT-PCR and analysed the GnRHR gene for the presence of mutations in its coding region, using direct sequencing of PCR products. Results were analysed according to the pattern of expression of alpha, beta-FSH and beta-LH subunit (SU) genes.RNA was extracted from 20 gonadotroph tumours identified by immunohistochemistry (10% of stained cells): 9 adenomas were functioning (high serum gonadotrophin levels), 3 were associated with high alpha-SU levels and 8 were nonfunctioning. Genomic DNA was extracted from 64 normal subjects.We found GnRHR mRNA in 12 tumours (60%): 8/9 functioning (88%), 1/3 alpha-secreting (33%) and 3/8 nonfunctioning (37.5%) gonadotroph adenomas. There was a significant association between GnRHR expression and immunostaining for beta-FSH (P = 0.014). The nucleotide sequence of the amplified products was identical to that of human pituitary except for the presence, in 3 functioning adenomas, of a silent C to T transition at nucleotide 453 encoding for the serine residue situated in the second intracellular loop at position 151. Heterozygosity provided evidence that both alleles were transcribed in these tumours. This substitution creates a Mae III restriction site. Genomic DNA from normal subjects were then tested for the presence of this new polymorphism. The frequency of the heterozygosity (18.7%) was not significantly different from that found in gonadotroph tumours (25%) and this new Mae III polymorphism site cannot be used as a tumoural marker.The GnRHR gene is preferentially expressed in functioning rather than in nonfunctioning gonadotroph adenomas, but no mutations altering the coding region of the gene were found to further substantiate its role in the pathogenesis of gonadotroph tumours.

We report an unusual case of a gonadotroph adenoma in a 34-yr-old woman, revealed by a dramatic rise in the plasma estradiol (E2) concentration (26,800 pmol/L; normal,370), with nonsuppressed FSH and LH levels (4.9 and 2.4 mIU/mL, respectively). The PRL level was 503 ng/mL. The testosterone and progesterone levels were 7 and 17 nmol/L, respectively. The levels of inhibin alpha, inhibin A, and inhibin B were increased compared to normal values in both the follicular (fp) and luteal (lp) phases of the menstrual cycle [inhibin alpha, 1986 IU/L (fp normal,700; lp normal,1650); inhibin A, 254 pg/mL (fp normal,20; lp normal,120); inhibin B, 246 pg/mL (fp normal,150; lp normal,30 lp)]. Pituitary magnetic resonance imaging revealed a huge pituitary adenoma. After transphenoidal surgery, the patient presented with pituitary insufficiency and diabetes insipidus. RT-PCR of the tumor tissue was positive for LHbeta, FSHbeta, alpha-subunit, and PRL. This case is of particular interest because 1) although the E2 level was extremely high, the patient did not present with ascitis, suggesting that chronic elevated E2 does not play a crucial role in the hyperstimulation symptoms; 2) the extreme rise in E2 was related to the cosecretion of FSH and LH, confirming the two-cell two-gonadotropin theory; and 3) the rise in inhibin B is associated with FSH secretion, whereas the rise in inhibin A is probably due to luteinization.

Treatment of prostatic cancer with GnRH agonist is a medical alternative to surgical castration, although hyperstimulation of the tumor can occur. We describe an unusual unwanted effect of such a treatment which unmasked a clinically silent gonadotroph adenoma. A 62-year-old man developed after the first injection of leuprorelin-depot a sudden intracranial hypertension, which was related to apoplexy of an unknown pituitary adenoma. Its gonadotroph origin was recognized after surgery by immunocytochemistry. Retrospectively, the tumor was shown to secrete in vivo both FSH and LH when on therapy with the agonist, demonstrating the lack of desensitization. Testosterone levels were also markedly and sustainly high when on therapy, a particularly unwanted effect in prostatic cancer. As gonadotroph adenomas occur in men in the same age group as prostatic cancer, the question is raised whether hormonal testing and pituitary imaging should be performed before starting a therapy with GnRH agonist in men.

We evaluated the pituitary and gonadal suppression in 40 girls and nine boys treated with depot leuprorelin (3.75 mg sc if body weightor = 20 kg, 1.87 mg if body weight20 kg) every 28 days for central precocious puberty. Gonadal suppression was obtained in most of the children with this dose: 3 months after initiation of the treatment, 85% of children had a peak plasma luteinizing hormone response to gonadotropin-releasing hormone3 IU/l and the gonadal axis remained suppressed throughout the duration of the study (up to 24 months). Four patients required higher doses of leuprorelin to achieve suppression. In two girls, a cutaneous reaction to the drug was associated with incomplete suppression and the treatment had to be interrupted. Plasma leuprorelin levels tended to increase from day 3 to day 28 after injection. Residual leuprorelin levels measured 28 days after injection were stable during the first year of the study. We conclude that an initial dose of depot leuprorelin of 3.75 mg sc every 28 days is efficient in most children with central precocious puberty.

Seven women suffering from hypogonadism due to previous hypophysectomy, isolated gonadotrophin deficiency, or Kallman's syndrome [median age 39 years (range 24-45)] volunteered to participate in a study to assess ovarian response following multiple-dose administration of recombinant human follicle-stimulating hormone (rhFSH; Org 32489). Baseline serum FSH and luteinizing hormone (LH) concentrations were 0.25 (0.05-1.15) IU/l and 0.06 (0.05-0.37) IU/l, respectively. Subjects received daily i.m. injections of rhFSH for 3 weeks (week 1: 75 IU/day, week 2: 150 IU/day, week 3: 225 IU/day). Blood sampling and sonographic investigations were performed on alternate days. Steady-state FSH concentrations were reached approximately 3-5 days after alterations of the doses administered. Maximum FSH concentrations were between 7.1 and 11.8 IU/l, whereas serum LH concentrations remained unchanged. Due to absent follicle development and lack of a rise in immunoreactive inhibin (INH) (response failure possibly due to early ovarian failure or resistant ovary syndrome) in two subjects, analysis of ovarian response was restricted to five volunteers. Serum androstenedione levels showed no significant changes during rhFSH administration. Although serum immunoreactive INH concentrations reached normal late follicular values [659 (388-993) IU/l], serum oestradiol revealed only a minor increase [77 (18-210) pmol/l]. Moreover, growth of (multiple) ovarian follicles was observed up to pre-ovulatory sizes (15 mm) in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The blue fox is a monestrous seasonal breeder with a pro-oestrus and oestrus lasting several days and a prolonged luteal phase in non-pregnant as well as pregnant vixens. Ovulation occurs 2 days after the preovulatory luteinizing hormone (LH) peak at the onset of oestrus; oocytes are ovulated as primary oocytes and maturation is completed 2-3 days later. Fertilization is possible during all stages of oocyte maturation until degeneration of oocytes 5 or 6 days after the LH peak. In this study, changes in plasma concentrations of follicle-stimulating hormone (FSH) and immunoreactive inhibin (iINH) and their relationships with LH, oestradiol, androstenedione, testosterone and progesterone secretion and with the periovulatory events, were determined throughout the reproductive cycle of 14 vixens. In late anoestrus and pro-oestrus, FSH and iINH were inversely related to each other (r = -0.84, P0.001); whereas FSH concentrations declined to reach low values within the 5 days preceding the LH peak, iINH secretion increased, as did that of oestradiol and androgens. Thereafter, iINH and steroid concentrations with the exception of progesterone reached maximal values at the time of the LH and FSH peaks and decreased within the following 2-3 days in the early luteal phase. Progesterone started to increase simultaneously with the LH peak, and when oocyte maturation was completed (around day 4), progesterone concentrations were increasing, while those of other hormones were low. A postovulatory release of FSH was detected between days 6 and 10; it preceded the rise in iINH, which began on day 8 when concentrations of progesterone were already high and those of oestradiol and LH were low. Progesterone and iINH were positively correlated over the period day 6 to day 49 (r = 0.62, P0.01). These results indicate that, in the blue fox, iINH is secreted by the preovulatory follicle and the corpus luteum; that during pro-oestrus, iINH may act in synergy with oestradiol to reduce the secretion of FSH and that after the LH peak the decrease of iINH and oestradiol concentrations may be responsible for the postovulatory release of FSH, which in turn causes an increase in iINH, possibly secreted by the corpus luteum and, as a result, FSH secretion is suppressed.

L’insuffisance ovarienne (IO) est frequente apres transplantation medullaire et conditionnement par le Busulfan ou une irradiation corporelle totale. Les effets des autres chimiotherapies a haute dose (CHD) sont mal connus. La fonction ovarienne a ete evaluee chez 29 femmes, âgees de 11 a 31 ans (moyenne : 20,1 ± 5,4), ayant recu une CHD sans Busulfan, ni radiotherapie avec un recul moyen de 13,2 ± 6 ans (1,5 a 24 ans), a un âge moyen de 6,9 ± 5,2 ans (1,5-15 ans) et chez 13 controles. 10 femmes (35 %) ont developpe une IO avec amenorrhee. Ces patientes avaient des taux de FSH et LH eleves et des taux d’inhibine B (p = 0.01) et d’hormone antimullerienne (AMH) (p = 0.002) significativement inferieurs a ceux des femmes ayant des regles spontanees et des controles. Les 19 autres patientes (65 %) ont ete reglees a un âge moyen de 12,8 ± 1 ans, de facon reguliere et 3 ont eu des grossesses spontanees. Cependant, des anomalies significatives du bilan ovarien ont ete observees chez les femmes sans contraception orale (n = 14) par comparaison aux controles : taux superieurs de FSH 6,8 ± 2,5 UI/l v 5,2 ± 0.8 (p = 0.012), taux inferieurs d’AMH 4,2 ± 1,8 pmol/l v 23,9 ± 5,4 (p = 2.10-9), ovaires plus petits 27,5 ± 6,6 mm v 31,6 ± 2,7 (p = 0.06) et comportant un plus faible nombre de follicules antraux > 2 mm 3 ± 3 v 11 ± 3 (p = 0.0001). Les taux de LH et d’inhibine B n’etaient pas significativement differents. Le taux d’AMH etait correle au nombre de follicules ovariens (p = 0.01). Parmi les 22 femmes traitees a un âge pre pubertaire, seules 3 (13 %) avaient une IO. Inversement, les 7 femmes transplantees pendant ou apres leur puberte ont developpe une IO. 90 % des filles âgees de 12 ans ou plus au moment de la CHD ont developpe une IO versus seulement 5 % des plus jeunes (p En terme de chimiotherapie, le Thiotepa etait associe a un risque eleve d’IO complete (p = 0.002 ; OR 10.1). Conclusions 1) Malgre des cycles reguliers, de nombreuses jeunes femmes ayant recu une CHD ont une alteration des taux de FSH et d’AMH et un nombre reduit de follicules antraux, temoignant probablement d’une reduction de la reserve ovarienne. 2) Le risque d’insuffisance ovarienne complete est lie a l’âge, au stade pubertaire au moment de la chimiotherapie a haute dose et a l’utilisation du Thiotepa.

For a better definition of the factors which could be at the origin of neonatal distress, 357 cases of mono-fetal term pregnancies with breech presentation were retrospectively studied between January 1st, 1984 and December 31st, 1989. The population is identical to that of all deliveries except for a higher percentage of first pregnancies. The risk of emergency caesarean section mostly concerns large primiparous women, underweight, with normal or large pelvis. Caesarean section is absolutely necessary if the biparietal diameter exceeds 100 mm, if the head is positioned in hyper-deflection and/or if the pelvis is defective. Without being mandatory, the procedure is preferable in case of chronic fetal distress or scarred uterus. On the contrary, neither the age of the mother nor the age of the pregnancy, nor the type of the breech, nor the number of pregnancies have any effect on the prognosis. The current rate of caesarean section is 47.9 per cent with almost complete disappearance of the large breech extraction (0.6 per cent) and the Mauriceau's maneuver (0.3 per cent). The corrected mortality rate is 0.28 per cent. In addition to the parameters considered in our coefficient of risk of breech delivery, it was noted that a pre-pregnancy weight exceeding 70 kg or a weight gain of more than 15 kg represent unfavorable factors. It is desirable to calculate prospectively the severity of the risk in small size cases, when the biparietal diameter ranges between 96 and 100 mm, or when one of the diameters of the bony pelvis is decreased.

The suppressive effect of the gonadotropin-releasing hormone (GnRH) antagonist Nal-Glu ([Ac-D2Nal1, D4ClPhe2, D3Pal3, Arg5, D-4-p-methoxybenzoyl-2-aminobutyric acid6, DAla10]-GnRH), injected intramuscularly with 5 mg, was studied in six men. Testosterone decreased by 87 +/- 2.3%, whereas the mean drops were 50 +/- 10%, 43 +/- 6.6%, and 39 +/- 5.6% for radioimmunoassayable luteinizing hormone (LH), follicle-stimulating hormone, and free alpha-subunit, respectively (mean +/- SEM). Immunological characteristics of plasma LH were modified during the inhibition and recovery phases as evidenced by comparison between polyclonal and monoclonal assays. In two additional subjects sampled every 10 minutes, both LH and alpha-subunit pulses were suppressed by NalGlu injection and restored by pulsatile GnRH infusion. However, a nonpulsatile and possibly non-GnRH-dependent alpha-subunit secretion was maintained after NalGlu administration.

Long term administration of GnRH agonists is currently considered as the treatment of choice for precocious puberty. For the first time, we have at our disposal an efficacious and specific treatment of the disorder responsible for the syndrome called precocious puberty. Whether of idiopathic or neurogenic origin, true precocious puberty is primarily a hypothalamo-pituitary disorder. It is at this location that the GnRH agonists exert their effect. Knobil’s experiments in monkeys [1] provided a rationale for agonist treatment by showing that continuous infusion of GnRH caused suppression of gonadotropin release. Our understanding of the mechanism of action of GnRH agonists is however incomplete and many questions arise when the gonadotropin secretory patterns during agonist treatment are considered.

Thirty cryptorchid boys with pre-scrotal testes were divided in two groups: Group 1 (3 bil/12 unil)received hCG (750U/m2/dose)+hMG (100U/m2/dose) 2 times weekly, during 6 weeks; Group II (5 bil/10 unil) received only hCG. Surgical correction was necessary in 28 cases, 22 of wich had a testicular biopsy and subsequent hystomorphological analysis. Results were obtained in basal condition and at 3rd. and 6th. weeks of treatment. Peak values are showed: T=topic C=cryptorch. Sperm=spermatogonia/50 tubes At=tubular area. LH(mUI/ml) FSH(mUI/ml) Testosterone (ng/dl) inhibin (UI/L). There was no advantage in hMG association. The hormonal level fell between 3rd 6th weeks (down-regulation). There was no correlation between inhibin levels and testosterone, spermatogonia or tubular area. Tubular area and number of spermatogonias were decreased on the affected side in relation to the topic testes and in bilateral cases in relation to the normal patterns.

We have studied the cathodoluminescence of single crystals of Cu In S 2 obtained by iodine chemical transport. As grown crystals and crystals annealed in In, S, (In + S), or in vacuum, were used. Two types of spectrum were observed, one for n type crystals due to S vacancies, and the other for p type or compensated crystals, which is interpreted as donor-acceptor pair transitions (determined by Time Resolved Speetroscopy) between the S vacancy (donor ~90 meV) and the Cu vacancy (acceptor ~45 meV), and by the corresponding free-to-bound transitions.

The edge luminescence of CuGaSe2 is studied on single crystals, from liquid helium temperature to room temperature. Time resolved spectroscopy measurements permit us to describe one of the emission bands in terms of donor‐acceptor pair transitions. Three other emission bands are observed. We attribute them to free‐to‐bound transitions. We determine three impurity levels: 110, 80, and 50 meV. Annealings in different atmospheres permit us to think that the 50‐meV level is due to a cation vacancy acting as an acceptor, and the 80‐meV level to a Se vacancy, which would act as a donor [Migliorato et al., J. Appl. Phys. 46, 1777 (1975)].

To investigate the efficacy of the different routes of luteinizing hormone releasing hormone (LHRH) administration upon pituitary responsiveness, we compared plasma LHRH concentrations and pituitary LH responses in four patients with hypothalamic amenorrhea treated with pulsatile LHRH. A portable computerized infusion pump delivered sc or iv LHRH pulses of 5, 10 or 20 micrograms every 90 min. Comparison of the two modes of LHRH delivery was performed using radioimmunoassay of exogenous LHRH and studying its pharmacokinetics for a 3 pulses period. With 10 micrograms of LHRH given iv, plasma LHRH levels increased between 700 and 1000 pg/ml within 3 min and returned to basal levels in 30 min. When given sc (10 micrograms), plasma LHRH levels peaked between 80 and 100 pg/ml in 15 min and returned to basal levels 60 min later. In one patient treated with 5 micrograms per pulse iv or sc, plasma LHRH increased to 380 and 60 pg/ml respectively. In all patients, computerized analysis of LH pulses was performed during sc and iv LHRH administration. LH pulsatile release displayed a similar rhythm period with both routes. However, for the same dose of LHRH (10 micrograms), the adjusted mean of LH plasma levels was lower with the sc route. In conclusions, the pharmacokinetics of LHRH administered sc or iv displayed a similar pattern but, with equivalent doses, higher plasma LHRH levels are attained with the iv route. Concomitantly, the mean LH levels were also greater after iv administration. Ovulation can be successfully induced by both pulsatile iv and sc LHRH therapy. However, with the sc route, a higher dose of LHRH should be used to prevent a delay of ovulation or a luteal deficiency.

We have studied the cathodoluminescence (edge emission) of single crystals of CuInS2 obtained by iodine chemical transport. Emission intensity as a function of excitation, temperature, and time [time resolved spectroscopy] allow us to reveal donor‐acceptor transitions. By fitting the TRS spectra, we calculate the ionization energy of the impurities involved: EA,D≃45 meV, ED,A ≃95 meV, as well as the maximum transition probability: WMAX≃108 s−1.

hCG is known to be produced by trophoblastic cells as well as by many normal tissues and malignancies. hCG is considered as a reliable marker for gonadal and extra gonadal choriocarcinomas; moreover it has been evidenced by immunohistochemical techniques in other malignancies. In this study, hCG and/or its alpha and beta subunits were detected in 73 males. Intact hCG was detected in 48 patients with gonadal tumors (n = 37) or extragonadal malignancies (n = 11), with or without free alpha or beta subunits. In the other 25 patients, native hCG was not detected but there were significant amounts of free beta subunit in 8 germ cells tumors and 17 extragonadal tumors. The production of free beta chains is correlated with a severe evolution in extragonadal tumors. hCG should be considered as a good marker for many tumors, but it is absolutely necessary to evaluate intact hCG as well as free beta chains.

The effect of long term treatment with D-Trp6-LH-RH in microcapsules (GnRH-A) on pituitary gonadal axis was studied in a adolescent and adult Fox-terrier dogs. They received intramuscularly 50 micrograms/GnRH-A/kg, on day 1 and 21 and every 4 weeks thereafter. Three adult dogs received 4 injections. cLH, cFSH and T levels were undetectable on day 7. Detectable then normal levels occurred 60 and 90 days respectively after the last injection on day 77. Testis thickness was respectively 22.1 +/- 0.8 mm and 16.3 +/- 0.8 mm on days 0 and 77; initial values were observed 90 days later. Spermatozoa disappeared from the ejaculate on day 21 in 2 dogs; reappearance and complete recovery were observed on days 161-175 and 252 respectively. Histological findings showed on day 91 atrophic lesions of testis and prostate and spermatogonia were present in all seminiferous tubules. After recovery a normal histological appearance was noticed. Three adolescent 29 weeks old dogs received 14 injections, the last one on day 357. cLH, cFSH and T levels were undetectable only from day 105. Testis thickness were respectively 15.8 +/- 0.7 mm, 18.1 +/- 0.7 mm, 12.5 +/- 0.3 mm and 21.4 +/- 0.7 mm on day 0, 21, 357 and 490. Initially, no spermatozoa were present in the ejaculates, they appeared in 2 dogs after 2 months for 20 to 40 days then disappeared until day 449. Normal semen characteristics were observed in all three dogs on day 581. Histological findings on day 371 were comparable to those observed in the adult dogs. This study demonstrates that longterm treatment with D-Trp6-LH-RH in microcapsules leads to a reversible inhibition of spermatogenesis in dogs. The delayed response in adolescent dogs might be due to a transient resistance to therapy related to.

2900 records of deliveries occurring at a clinic in Casablanca between January and April 1979 were analyzed to identify factors influencing birth weight. Of the 2575 newborns with healthy mothers, 2353 were full term and weighed over 2500 g, 94 were full term and weighed less than 2500 g, and 128 were premature. 253 of the 2900 mothers suffered from toxemia of pregnancy, 30 had diabetes, 21 had pulmonary tuberculosis, 12 had cardiac problems, and 9 had other ailments; 30 of their babies were premature. Average birth weight was 3392 g for mothers of higher socioeconomic level, 3280 g for middle level, and 3070 g for lower level. Average weights were 3230 g for 1st births, 3426 g for 2nd births, 3494 g for 3rd-5th births, and 3620 g for subsequent births. Babies of women under 20 weighed the least; birth weights increased with maternal age and stabilized after 30. Babies of married women weighed on average 257 g more than those of single women. Babies of mothers having at least 1 prenatal consultation were 102 g heavier. Babies of women with no previous abortion, stillbirth, or premature birth were 70 g heavier. Male babies weighed 138 g more than female. Lowest birth weights were among babies with mothers weighing under 50 kg and under 145 cm tall. Babies born at 28 weeks weighed 1081 g, at 32 weeks 1814 g, and at 36 weeks 2472 g. 47.64% of premature births occurred to primaparas. 303 infants weighed more than 4000 g. Newborns of mothers with toxemia but no other illness weighed 3247 g. Over 20% of babies carried to term by mothers with toxemia weighed less than 3000 g. Birth weight decreased with increasing severity of toxemia. Average weight for mothers with diabetes was 3864 g. Of 50 babies weighing under 3000 g at birth, 2 had deficient Apgar scores, 15 weighed less than 2500 g and 5 less than 2000 g, and 17 died, of which 9 weighed less than 2500 g and 4 less than 2000 g. Regional studies disclosed that average birth weight in a maternity center in El Jadida was 3408 g, with males weighing 107 g more, and with weights generally increasing by parity and maternal age, height, and weight. Average birth weights in Fez were 3350 with males weighing 140 g more. Birth weights were correlated with parity and maternal weight but not maternal height. Average birth weights in the studies were higher than expected, and the number of low birth weight infants was less than expected.

Receptors for Epidermal Growth Factor (EGF) have been identified in different types of tumors and they are often associated with other characteristics which are related to a bad prognosis. A technic has been established to measure membrane receptors in human placenta, which is appropriate for the study of tumors. Preparations of placental membranes were incubated either with increasing amounts (0.1 to 3.0, 10(-9) M) of EGF labeled with 125I (method by saturation) or with 0.2, 10(-9) M labeled EGF and increasing concentrations (0 to 1.6, 10(-9) M) of cold EGF (method by competition). The KD obtained with both technics are not significantly different: 0.85 and 0.77, 10(-9) M respectively, as well as the maximum binding capacity: 5.9 and 4.4 pmol/mg protein respectively. A preliminary study in breast tumors showed that 2 out of 9 contained significant amounts of receptors (58 and 114 fmol/mg protein). One of these two tumors held both estradiol and progesterone receptors. In the other 7 tumors without EGF receptors only one did not contained any estradiol or progesterone receptors. Further studies are needed to evaluate the relationships between EGF/sex hormone receptor status and the degree of breast tumor malignancy.