[Neoadjuvant chemotherapy, with mitoxantrone, cyclophosphamide and fluorouracil, in operable breast cancer of intermediate stage: first results of a phase II study in 40 patients]. / Chimiothérapie néoadjuvante, à base de mitoxantrone, cyclophosphamide et fluorouracile, dans le cancer du sein opérable de stade intermédiaire: premiers résultats d'une étude de phase II sur 40 patientes.

Forty patients with intermediate stage (T2 > 3 cm-T3, N0-N1) operable breast cancer received neoadjuvant chemotherapy by MCF (mitoxantrone, cyclophosphamide, 5-fluorouracil). Four cycles were administered at 3-week intervals. The obvious hematological toxicity (64% of grade III for the leucocytes and up to 34% of grade IV for the granulocytes) was rapidly reversible and did not hinder completion of the treatment. Ten patients showed a complete remission and a tumor volume regression of more than 50% was observed in 12 other patients. Tumor shrinkage allowed breast-saving surgery in 50% of the cases. A complete sterilisation of the surgical specimen was found in only two of the 40 patients and a few persisting neoplastic cells were found in ten other cases. A positive response at the level of the axillary lymph nodes was also obtained in more than 50% of the cases. In 25 of the 36 cases examined, the primary chemotherapy induced cellular lesions (fibrosis, necrosis) at the tumor level. A feasibility study was undertaken in order to determine quantitatively several biochemical parameters (steroid hormone receptors, cathepsin D, c-erbB-2 oncoprotein) in very small tumor samples obtained by Tru-Cut before any treatment and in surgical specimens. In the future, these micromethods will be used systematically with the aim of estimating the value of these potential prognostic factors for therapeutic follow-up of the patients.

[Biochemical characterization of a high-molecular weight alkaline phosphatase in a patient with cholangiocarcinoma (alpha-1 alkaline phosphatase)]. / Caractérisation biochimique d'une phosphatase alcaline de haute masse moléculaire chez un patient atteint de cholangiocarcinome (alpha 1-PAL).

The authors analysed the alkaline phosphatases present in the serum of a patient with cholangiocarcinoma. The electrophoretic analysis on cellulose acetate revealed two bands of AP activity in positions alpha 1 and alpha 2. The more anodic of the isoenzymes of AP presented most of the features of the high molecular weight isoenzyme found in human bile, except that it was non-competitively inhibited by L-homoarginine. This feature, which distinguishes this isoenzyme form the biliary isoenzyme of AP, indicates the existence of another type of high molecular weight isoenzyme present in malignant hepatic diseases.

Ovarian function is effectively inhibited by a low-dose triphasic oral contraceptive containing ethinylestradiol and levonorgestrel.

For various metabolic and clinical reasons, it has been strongly advocated to reduce the dose of both the estrogen and progestogen components of oral contraceptives (OCs). In this study, we compared after 6 months of treatment, the action on various hormonal parameters of a standard-dose combined OC containing ethinylestradiol (EE) 0.050 mg and levonorgestrel (LNg) 0.250 mg and a low-dose triphasic combination containing a 59% reduced amount of the same steroids. Hormonal measurements in the last 3 days of OC intake indicated that basal levels of FSH and LH were less inhibited by the low-dose preparation, while PRL levels were unchanged. However, gonadal function was effectively inhibited by both high and low dose OCs, as demonstrated by equally low levels of E2, E1, P and 17-P. Consequently, no residual gonadal function could be anticipated from the observed low steroid concentrations. These results corroborated other studies (reviewed in this paper) in which serial hormonal measurements also revealed a complete lack of follicular maturation during low-dose triphasic OC treatment. Moreover, inhibition of circulating levels of A, DHEA, DHEAS, free T and DHT was similarly obtained with both preparations. Collectively, these data indicate that ovarian function is as effectively inhibited by a low-dose triphasic preparation as by a higher, standard-dose OC containing the same steroids.

PIP: For various metabolic and clinical reasons, it has been strongly recommended that the dose of both the estrogen and progestogen components of oral contraceptives (OCs) be reduced. In this study, the authors compared, after 6 months of treatment, the action on various hormonal parameters of astandard-dose combined OC containing ethinyl estradiol (EE) 0.050 mg and levonorgestrel (LNg) 0.250 mg and a low-dose triphasic combination containing a 59% reduced amount of the same steroids. Hormonal measurements in the last 3 days of OC intake indicated that basal levels of FSH and LH were less inhibited by the low-dose preparation, while prolactin (PRL) levels were unchanged. However, gonadal function was effectively inhibited by both high and low dose OCs, as demonstrated by equally low levels of E2, E1, P, and 17-P. Thus, no residual gonadal function could be anticipated from the observed low steroid concentrations. These results corrborated other studies (also reviewed in this paper) in which serial hormonal measurements also revealed a complete lack of follicular maturation during low-dose triphasic OC treatment. Moreover, inhibition ofcirculating levels of A, DHEA, DHEAS, free T and DHT was similarly obtained with both preparations. Collectively, these data indicate that ovarian function is as effectively inhibited by a low-dose triphasic preparation as by a higher, standard-dose OC containing the same steroids.

The expression of different monooxygenases supported by cytochrome P-450 in neonatal rats and in primary fetal hepatocytes in culture.

In rat liver, the perinatal development of various monooxygenase activities follows different patterns, depending upon the reaction studied. The ontogeny of the 6 beta-, 7 alpha- and 16 alpha-testosterone hydroxylase activities differs very significantly. Aldrin epoxidase and steroid-metabolizing monooxygenases are expressed in primary fetal rat liver cells in culture after treatment in vitro with dexamethasone. Testosterone is not metabolized by the control cells and is hydroxylated on the 6 beta and 16 alpha positions following the addition of corticoids to the culture medium. The dose and time curves vary according to the hydroxylated position of the steroid. Aldrin epoxidase activity is nearly undetectable in the control cells, but is present and is inducible by phenobarbital following treatment with the corticoid. Phenobarbital induces aldrin epoxidase in the absence of dexamethasone in the culture medium, providing that the cells are pretreated with the corticoid for 48 h. The use of antibodies against the main cytochrome P-450 species purified from adult and phenobarbital-treated rats confirms that a similar cytochrome P-450 can be induced in fetal cells in culture. The perinatal regulation of biological events, such as the expression of the monooxygenases, can be reproduced in fetal rat liver cells in culture; such a model constitutes a unique tool for studying the biochemical mechanisms which control these phenomena.

Plasma hormone levels in women receiving new oral contraceptives containing ethinyl estradiol plus levonorgestrel or desogestrel.

The changes in plasma hormone levels were evaluated in matched healthy female volunteers investigated before and after 6 months' use of three new oral contraceptives (OCs): TrigynonR (n = 13), a triphasic OC containing low doses of ethinylestradiol (EE) + levonorgestrel (LNg); MarvelonR (n = 14), a monophasic OC containing low doses of EE + desogestrel (DOG, a new progestogen derived from LNg); and OvidolR (n = 10), a sequential OC containing higher doses (50 micrograms) of EE + DOG. Serum levels of FSH, LH, estradiol and progesterone were decreased in all cases to levels incompatible with ovulation. Prolactin concentrations were unchanged. Sex hormone binding globulin (SHBG) and Transcortin (CBG) levels were significantly increased by all three OCs (Ovidol greater than Marvelon greater than Trigynon); free testosterone levels decreased significantly while free cortisol concentrations remained unchanged. Collectively, these data indicate that (a) all three OCs are effective ovulation inhibitors, (b) Ovidol and Marvelon have greater estrogenic effects than Trigynon, (c) LNg is more effective than DOG in reducing the EE-induced increase in SHBG levels, and (d) free testosterone levels are equally well suppressed by all three Ocs.

[Kaposi's sarcoma in Haiti: unknown reservoir or a recent appearance?]. / Le sarcome de Kaposi en Haiti: foyer méconnu ou récemment apparu?

For a 29 months period, from June 1979 to November 1981. 11 cases of Kaposi Sarcoma (3 women and 8 men) have been diagnosed in Port-au-Prince. Two more cases (men) were seen in haitian refugees in Miami (C. D. C. report). Only one case of K. S. had been diagnosed in Haïti previously in 1972. The mean age was 37. Involvement of lymph nodes and viscera were frequent and the patients died within 24 months (the mean survival time after diagnosis was 5 months). This apparent outbreak probably has no relation with that one in U. S. homosexuals which appeared simultaneously. Drugs and homosexuality have no importance in haitian cases. K. S. in U. S. homosexuals and in heterosexual haitians has a bad prognosis as in Africans: they all differ from the classical european and north american forms by the age of onset, the frequent visceral involvement and the early death. The review of histological data and different etiological factors lead to think that it is the same disease everywhere in spite of those marked differences.

Comparison of levels of cytosol estrogen receptors with "arterial" and "venous" concentrations of gonadic steroids in mammary tumors.

Plasma steroid concentrations measured in the post-menopausal women with breast cancer showed a close correlation between the various androgens. The post-menopausal women exhibited a correlation between estrogen receptors (ER) and "arterial" 17 alpha-hydroxyprogesterone levels in the breast. ER levels expressed as a function of plasma (arterial) steroid (P/17 P) molar concentration ratio were distributed within a hyperbola, suggesting the existence of a control mechanism for breast cell ER levels.

[Prenatal diagnosis of sex by determination of amniotic testosterone and FSH]. / Diagnostic prénatal du sexe par dosage de la testostérone et de la F.S.H. amniotiques.

Among hormones which can be determined in the amniotic fluid in the mid-pregnancy period, testosterone and F.S.H. allow the best discrimination between sexes (Figure 1). Moreover, F.S.H. is clearly increasing during the 2d trimester of pregnancy in case of a female fetus. This is a quick and reliable method which uses a small quantity of amniotic fluid. Combined with chromosomal analysis, it increases the accuracy of the sex diagnosis and indicates a repeat amniocentesis if there is a discrepancy between karyotype and hormonal determinations.

Measurement of gonadotrophins, testosterone, delta4 androstenedione and dihydrotesterone in idiopathic oligospermia.

Basal concentrations of FSH, LH, testosterone, delta4 androstenedione and dihydrotestosterone, together with FSH and LH responses to single injections of LHRH were determined in eighty-four patients with oligospermia and in twenty-seven normal men. LHRH responses were heterogeneous and indicate that various disorders might cause this syndrome. In six cases there appeared to be an isolated deficiency in spermatogenesis, as indicated by an increased FSH response, whilst the LH response was normal as were the concentrations of the testicular hormones. In twenty cases a concomitant disorder of Leydig cell function and spermatogenesis is suggested as indicated by increased FSH and LH responses and decreased concentrations of testosterone and delta4 androstenedione (six) or concentrations at the lower limit of normal (fourteen). Furthermore, in five cases a hypothalamic and/or pituitary disturbance may be accepted on the basis of normal or decreased basal concentrations decreased and responses to LHRH with decreased concentrations of testosterone and delta4 androstenedione. Finally, in thirty-seven cases, oligospermia was not associated with any modification basal gonadotrophin concentrations or response to LHRH when compared with normal subjects.

[Enzyme-linked immunosorbent assay (ELISA) (author's transl)]. / Immuno-enzymologie: système ELISA.

The development of enzymo-immunological technics and the synthesis of efficacious immuno-adsorbants has given rise to several immuno-enzymometric methods of which one, ELISA (enzyme-linked immunosorbent assay) has proved particularly practical and sensitive for the estimation of antibodies.

Enzymatic properties of prostaglandin synthetase from bovine seminal vesicles.

The relative quantities of PGE2 and PGF2alpha biosynthesized are strictly dependent on the concentration of the precursor, arachidonate, on the nature and on the quantity of sulfhydrylated cofactor present. The sigmoid aspect of the curve of PGF2alpha biosynthesis as a function of arachidonate concentration is directly dependent on the GSH concentration. Treatment of the microsomes by low concentrations of HgCl (5 muM) modifies the kinetics of PGE2 and PGF2alpha biosynthesis. Similarly, the presence of L-8027, a competitive inhibitor, alters qualitatively and quantitatively the production of PGE2 and PGF2alpha as a function of arachidonate concentration.