[Liver transplantation for hepatopulmonary syndrome complicating cirrhosis]. / Transplantation hépatique pour syndrome hépatopulmonaire compliquant une cirrhose.

Hepato-pulmonary syndrome (HPS) is a pulmonary vascular complication of cirrhosis quite frequent but often under-diagnosed, and characterized by intra-pulmonary capillary and pre-capillary vascular dilatations that may lead to severe hypoxemia. HPS is often asymptomatic but may induce a progressive dyspnea. HPS diagnosis is based on arterial gasometry that proves the hypoxemia and contrast-enhanced echo-cardiography revealing the vascular dilatations. Screening of HPS is recommended in every cirrhotic patient complaining of dyspnea or in every liver transplantation candidate. Indeed, the only effective treatment of HPS is liver transplantation; HPS patients receive exception-points in the MELD (Model for End-Stage Liver Disease) liver allocation score. The authors report herein the case of a 39-year-old male patient with a cirrhosis of unknown origin complicated by HPS which appeared as a disabling dyspnea. This patient underwent liver transplantation a year after HPS diagnosis and recovered completely.

Le syndrome hépatopulmonaire est une complication vasculaire pulmonaire de la cirrhose relativement fréquente et sous-diagnostiquée, caractérisée par des vasodilatations capillaires et pré-capillaires intrapulmonaires pouvant entraîner une hypoxémie sévère. Souvent asymptomatique, ce syndrome se révèle le plus souvent par une dyspnée d'apparition progressive. Le diagnostic est réalisé par une gazométrie artérielle prouvant l'hypoxémie et une échographie cardiaque de contraste démontrant l'existence de vasodilatations intrapulmonaires. Le dépistage du syndrome hépatopulmonaire est préconisé chez tout patient atteint de cirrhose présentant de la dyspnée et chez tout patient candidat à une greffe hépatique. En effet, le seul traitement efficace est la transplantation hépatique, et ces patients bénéficient d'ailleurs de points d'exception dans le calcul du score de MELD («Model for End-Stage Liver Disease¼). Nous rapportons ici le cas d'un patient de 39 ans atteint d'une cirrhose d'origine indéterminée compliquée d'un syndrome hépatopulmonaire qui s'est révélé par une dyspnée devenue rapidement invalidante. Ce patient a pu bénéficier d'une transplantation hépatique un an après le diagnostic de syndrome hépatopulmonaire, permettant ainsi une guérison complète tant sur plan hépatique que pulmonaire.

[An unusual interstitial pneumonitis]. / Une pneumopathie interstitielle inhabituelle.

We report the case of a twenty-six-years-old patient who developed acute silicosis after only five years of professional exposure. He also succeedingly presented in the course of the disease progressive massive fibrosis, rest hypoxia, and eventually spontaneous pneumothorax. Monopulmonary transplantation was finally successfully performed.

Influence of chlorpromazine on the positive and negative feed-back mechanism of oestrogens in man.

PIP: It was determined whether all the different neuroendocrine actions of estrogen are competitively antagonized by phenothiazines to test the putative analogy between the 2 types of molecular receptor. 12 men aged 22-25 years were tested on 3 days and then given 2 X 20 mg ethinylestradiol (EE) for 4 days with either 2 X 50 mg chlorpromazine (6 cases) or a placebo (6 cases). Neurohypophyseal activity and adenohypophyseal activity were tested. There was a lack of significant changes in pulse, blood pressure, body weight, and psychosexual factors. Blood alkaline phosphatases decreased in all 12 men after estrogen, and an inhibitory effect of estrogens alone was seen on blood FSH and on the 2 and 5 fraction of urinary 17-keto-steroids. The neurophysine basal level and the growth hormone peak response to hypoglycemia showed a stimulatory effect. There was no effect on FSH by chlorpromazine or on the inhibition of 17-keto-steroids due to estrogens. However, chlorpromazine lessened the neurophysine increase and abolished the facilitatory effect of estrogens on growth hormone responsibeness to hypoglycemia. In 60% of the cases TSH blood levels were undetectable and unvaried.^ieng

Absence of predictive value of follicular inhibin on the results of human in vitro fertilization.

During the periovulatory period, inhibin did not have a discriminant role in oocyte fertilizability. A possible role in the gonadotropin surge was not revealed by analysis at the time of follicular rupture. Furthermore, inhibin activity appears to be very low. But inhibin could still have an effect upon growth and atresia of the follicles of the following cycles.

Inhibin concentration in the culture media of human oocyte-cumulus-corona cell complexes is not related to subsequent embryo cleavage.

We have demonstrated an in vitro secretion of inhibin by human OCCC, not related to subsequent egg cleavage. A putative signal, released by OCCC, that could modulate inhibin secretion by granulosa cells has not been discovered. Inhibin secretion by OCCC has no predictive value concerning the further fertilization and cleavage of the oocytes.

Variations of luteinizing hormone serum concentrations after exogenous human chorionic gonadotropin administration during ovarian hyperstimulation.

Changes in luteinizing hormone (LH), estradiol, and progesterone (P) serum levels before and after preovulatory administration of human chorionic gonadotropin (hCG) were assayed in 30 patients stimulated with clomiphene citrate (CC) and human menopausal gonadotropin (hMG) and compared with LH variations in 43 patients submitted to pharmacological hypophysectomy with a gonadotropin-releasing hormone agonist (GnRH-a) and stimulation with hMG. In CC + hMG-treated patients, an endogenous LH surge occurred systematically 4.25 +/- 2.75 hours after hCG injection. Multiparametric analysis indicated an inverse correlation between the delay in the initial rise of the LH surge and the increase in P levels during the 6 hours after hCG administration. Gonadotropin-releasing hormone agonist + hMG treatment did not lead to an LH surge after hCG but to a significant fall in LH levels. Thus, exogenous hCG, administered before ovulation, induces an endogenous LH surge if pituitary function is not blocked by a GnRH-a, probably through an increase in P secretion.

Laminin and type III procollagen peptide in human preovulatory follicular fluid.

The levels of laminin P1 fragment, a marker of basement membrane, and of the aminoterminal sequence of type III procollagen, a marker of interstitial connective tissue, were measured in human preovulatory follicular fluids. The concentrations of these peptides correlated with progesterone levels but not with those of estradiol or testosterone. Immunocytochemical studies confirmed the remodeling of the perifollicular basement membrane and interstitial matrix during oocyte maturation. The studies suggest that monitoring of the ovarian connective tissue macromolecules could be useful for estimating follicular maturation.

[Religion confronting insemination]. / La religion face à l'insémination.

The author attempts the difficult task of summarising the attitude of Catholicism, the Protestant religion, Jehovah's Witnesses, the Greek Orthodox and the Jewish Churches, as well as Islam, to artificial insemination, especially by donor. He discusses reasons for forbidding artificial insemination even from the husband because of onanism. He shows that the Protestant religion alone does not object to AIH and that its role as far as AID is flexible. As far as other religions AID is absolutely proscribed.

[Catecholamine conjugation during pregnancy]. / Conjugaison des catécholamines durant la grossesse.

Conjugated urinary catecholamines are increased during normal human pregnancy. The modification in the proportions of conjugated fractions are particularly significant for norepinephrine. They depend on the foetoplacental unit since delivery is followed by a reduction of the urinary concentrations of these conjugated fractions. Such a modification of catecholamine metabolism must be kept in mind when the level of sympathetic nervous system activity is studied during pregnancy.

[The normal testis: structure, function and recent endocrinologic advances]. / Le testicule normal: structure, fonction et acquisitions endocrinologiques récentes.

The embryology, the anatomy and the histology of the testis are briefly described. Then, the endocrinology of the organ is explained. Under the influence of pituitary LH, Leydig cells synthetize and release steroids that are principally testosterone. These act on the hypothalamo-pituitary axis, on the peripheral target organs and directly on the testis so as to control spermatogenesis and Sertoli cell function. Sertoli cells are implicated in spermatogenesis, steroidogenesis, and the synthesis of protein hormones and cybernin . Current knowledge about the antimullerian hormone, androgen binding protein, GnRH-like peptide, inhibin, testicular chalone, FSH receptor binding inhibitor and stimulator, PRL inhibiting substance and relaxin is reviewed.

[Endocrine, paracrine and autocrine mechanisms involved in follicular development]. / Mécanismes endocriniens, paracrines et autocrines du développement folliculaire.

Development of a single follicle during the menstrual cycle is under control of hormones stimulating follicular maturation, ovulation and luteogenesis. Several factors intervene locally to avoid other follicles developing at the same time as the dominant follicle. These other follicles remain quiescent or go on to atresia. Atresia results from the action of several endocrine, paracrine and autocrine mechanisms which synergistically inhibit aromatase activity. The subsequent lack of oestrogens reduces granulosa cell multiplication. The oocyte will not become fertilizable before the preovulatory peak of LH, after the resumption of meiosis and after reaching the metaphase of the second meiotic division. Several factors are involved in this inhibition of spontaneous resumption of meiosis: cyclic nucleotides, sex steroids, somatostatin, oocyte maturation inhibitor(s) (OMI). Ovulation is related to breakdown of connective tissue synthesized by granulosa cells under the influence of FSH. Connective tissue lysis is dependent on proteolytic enzymes which are released and activated by FSH, LH and relaxin. A paracrine control could be involved in ovulation: LH induces the production of prostaglandin and relaxin by theca cells which, in turn, stimulate collagenase and proteoglycanase secretion by granulosa cells.

[Monitoring of follicular growth. Significance of echography]. / Surveillance de la croissance folliculaire. Apport de l'échographie.

Follicular growth and ovulation may be estimated by various techniques: basal body temperature charts, cervical score and vaginal smears examination, gonadal steroids or gonadotropin measurement and more recently, pelvic echography. Echographic monitoring permits the determination of the number and the size of ovarian follicles and the prediction of the time of ovulation. 1065 cycles of patients consulting in an artificial insemination with donor semen program have been analyzed. Follicular growth is superimposable in spontaneous and hMG-induced cycles, but clomiphene treatment leads to the formation of larger follicles. Only one dominant follicle (greater than or equal to 15 mm) is generally observed in spontaneous cycles; multiple dominant follicles are visualized in respectively 11,8 and 24,3% cycles treated with either hMG or clomiphene. These follicles are localized in only one ovary in half of the cases. Consecutive monitoring in several cycles shows that the ovaries do not alternate systematically. While this type of monitoring does permit a reduction in the number of straws used, it does not improve the success rate of artificial insemination.

[Value of the measurement of SP1 protein in the early diagnosis of pregnancy induced with Pregnyl]. / Intérêt du dosage de la protéine SP1 dans le diagnostic précoce des grossesses induites par Prégnyl.

Successive dilutions of Pregnyl have been submitted to a radioimmunoassay of SP1. We have observed that Pregnyl cross-reacts with SP1. Chromatography of Pregnyl demonstrates that the contaminating substance is different from native SP1. As its concentration is low, it is however not detected in the serum of patients after the administration of exogenous Pregnyl. SP1 measurement can be helpful in detecting early pregnancies after hCG induction of ovulation.

[Inhibin: new gonadal hormone (author's transl)]. / Inhibine: nouvelle hormone gonadique.

There are many convincing arguments to accept the existence of inhibin. This hormone is produced inside the seminiferous tubules by the Sertoli cells in males and by the granulosa cells of the follicule in females. The biological, immunological and chemical characteristics of testicular and ovarian inhibin are identical so that it could be speculated the same molecule is secreted by both organs. This hormone is not a knownsteroid but is a protein substance. Thus, its biological activity is destroyed by trypsin and pepsin digestion and by heating at 60 degrees for 30 minutes. Furthermore, immunization with inhibin from rete testis fluid induces antibodies capable of neutralizing endogenous inhibin of adult male and female rats. This polypeptide hormone is not identical neither to ABP nor to a fragment of gonadotrophins. The molecular weight is not yet exactly defined and the possibility exists that two forms of inhibin are present in RTF: one of high (greater than 10,000 Daltons) and the other of low molecular weight. The high M.W. species could be a polymer or alternatively the combination of native inhibin and a carrier substance or unique precursor molecule. Inhibin preparations selectively depress the synthesis and the release of FSH in pituitary cell culture. The threshold dose to affect the LH production is higher than that active on FSH secretion. Furthermore, they reduce LH-RH content of hypothalamus maintained in organ culture. In animals, inhibin induced effects are depending on both hypothalamus and pituitary actions according to the functions of these two structures. In that sense, apparently contradictory results are obtained in short and long term castrated animals. Inhibin does not modify TSH, GH and prolactin in vivo and in vitro. This substance displays an inhibition on the synthesis of DNA in the testis of pubertal male rats and depresses the maturation of follicle in female.

[Origin and sites of action of inhibin (author's transl)]. / Origine et sites d'action de l'inhibine.

Mice testis in organ culture (31 degrees C) produce a steroid free substance which inhibits FSH secretion by rat pituitary cells. Histologically, Sterloti cells alone remain normal after a few days in culture. A hypothalamic action of inhibin is demonstrated in vitro. The intraglandular content in LHRH is inversely related to the amount of inhibin present in the culture medium. In the testis, DNA synthesis is depended of inhibin. This is demonstrated by studies of the incorporation of tritiated thymidine in testicular DNA in vivo and in vitro. In conclusion, inhibin is produced by Sertoli cells and acts not only at this pituitary level but also on the hypothalamus and the testis.

[Action of luteinizing hormone-releasing hormone (LH-RH) on gonadotropin secretion in normal subjects]. / Action de l'hormone hypothalamique libérant l'hormone lutéinisante (LH-RH) sur les gonadotrophines chez le sujet normal

PIP: Gonadotropin release after synthetic LH-RH injection was studied under a variety of experimental conditions. In male subjects, LH-RH (25 mcg) induces release of LH and FSH before and during puberty, but only of LH in adults. Larger doses of LH-RH do induce FSH release, with LH release proportional to LH-RH dose; FSH release is smaller than LH release and follows it. In prepuberal females, LH-RH induces a large release of FSH and a weak release of LH. In puberty, LH response becomes greater than FSH. In eugonadal women, FSH and LH responses are more marked during luteal phase than during preovulatory phase. Nonsequential hormonal contraceptives inhibit FSH and LH response to 50 mcg of LH-RH, but not to 100 mcg. In postmenopausal women, LH increases after 25 mcg of LH-RH; 200 mcg ethinyl estradiol for 5 days permits an increase of both gonadotropins. These results suggest that gonadotropin response to LH-RH depends on endocrine equilibrium and gonadal steroids which may modify the synthesis and/or release of pituitary gonadotropins. On the basis of selective LH response to small doses of LH-RH, ti is speculated that an FSH releasing factor may exist.^ieng

[Male infertility]. / Explorations en infertilité masculine.

In 2/3 of infertility problems, the male partner is, partially or entirely, responsible. His investigation starts with a careful history and is followed by a thorough physical examination. Then, comes the spermogram. In addition to an assessment of the number, motility, and morphology of spermatozoids, this examination must involve a spermocytogram, tests of anti-spermatozoid immunity, and a bacteriological analysis. The biological study of the seminal plasma is also of considerable value. Electron microscopy of sperm is valuable in asthenospermic men. A genetic and hormonal investigation is, nowadays, almost mandatory in all cases. Testicular biopsy with cryopreservation of testicular tissue and demonstration of a possible varicocele can also, in selected cases, be of great help. The overall strategy will be decided on the basis of the whole investigation.

[Male contraception]. / La contraception masculine.

PIP: Among the reasons why male hormonal contraception has lagged behind female methods are the necessity of preserving virility, the fact that spermatogenesis is a continuous process, the need to control secondary effects and toxicity, and the requirement that modes of administration be acceptable to both partners. Among currently available reversible mehtods, withdrawal is undoubtedly the most ancient. It is still widespread but cannot be recommended because of its limited effectiveness. The condom is used by about 10% of couples worldwide as a principal or temporary method, but its inter-ference with sensation has limited its acceptance. Condoms are nevertheless highly effective when used with a spermicide. Various androgens are currently under investigation. High doses of testosterone can induce azoospermia without affecting libido but their side effects may be serious. The use of combinations of steroids permits doses to be reduced and offers promise for the future. The combination of oral medroxyprogesterone acetate and percutaneous testosterone is one of the better approaches; the combination is effective and nontoxic but has the disadvantage of percutaneous administration. Gossypol, a pigment extracted from the cotton plant, has been used as a contraceptive in China with a reported efficacy of 99.89%, recovery of fertility within 3 months, and no effect on future fertility. However, its toxicity appears to be significant in the animal and its reversibility is uncertain. A search is on for analogs which would preserve the contraceptive effects while eliminating toxic effects. Several gonadotropin releasing hormone (GnRH) analogs under investigation for their interference with spermatogenesis have given promising results. Several chemicals tested for contraceptive effects have had unacceptably high toxicity. Chinese investigators have reported good results with various physical methods of interfering with sperm production, but their reversibility and innocuity have not been demonstrated. Among irreversible methods, many workers have sought an active or passive mehtod of immunizing against paregnancy, but no usable results have yet been obtained. Vasectomy is a simple and easy surgical procedure which is well accepted in some countries, although in most countries the responsibility for contraception is assumed by the women. Vasectomy has 1 advantage over female sterilization: sperm may be preserved in a bank for several years.^ieng

[Successful PMA. Review of the activities of the Center for Medically Assisted Procreation of University of Liege, 1985-1997]. / La PMA qui réussit Bilan d'activité du Centre de Procréation Médicalement assistée de l'ULg, 1985-1997.

Assisted reproductive treatments (ART) hold an increasing place in the field of female infertility but also of male infertility with the development of new micromanipulative technologies. From January 1985 to December 1997, more than 3,000 ovarian punctures were achieved at the CPMA of the University of Liege and more than 40,000 oocytes were recovered. Global results show a take home baby rate of 23% per ovum pick-up and 27% per embryo transfer. Embryo cryopreservation offers an efficient solution to the problem of supernumerary embryos and opens the way for IVF-derived procedures such as oocyte or embryo donation, surrogate mother. The transfer of frozen-thawed embryos increases the total ongoing pregnancy rate per cycle of 31%. One of the aims of our Centre in the near future is the development of new technologies such as control of chromosomal abnormalities or genetic defect in preimplantation embryos and clinical applications of oocyte or ovarian tissue freezing.