Second generation hybrid polar compounds are potent inducers of transformed cell differentiation.

Hybrid polar compounds, of which hexamethylenebisacetamide (HMBA) is the prototype, are potent inducers of differentiation of murine erythroleukemia (MEL) cells and a wide variety of other transformed cells. HMBA has been shown to induce differentiation of neoplastic cells in patients, but is not an adequate therapeutic agent because of dose-limiting toxicity. We report on a group of three potent second generation hybrid polar compounds, diethyl bis-(pentamethylene-N,N-dimethylcarboxamide) malonate (EMBA), suberoylanilide hydroxamic acid (SAHA), and m-carboxycinnamic acid bis-hydroxamide (CBHA) with optimal concentrations for inducing MEL cells of 0.4 mM, 2 microM, and 4 microM, respectively, compared to 5 mM for HMBA. All three agents induce accumulation of underphosphorylated pRB; increased levels of p2l protein, a prolongation of the initial G1 phase of the cell cycle; and accumulation of hemoglobin. However, based upon their effective concentrations, the cross-resistance or sensitivity of an HMBA-resistant MEL cell variant, and differences in c-myb expression during induction, these differentiation-inducing hybrid polar compounds can be grouped into two subsets, HMBA/EMBA and SAHA/CBHA. This classification may prove of value in selecting and planning prospective preclinical and clinical studies toward the treatment of cancer by differentiation therapy.

[Voluntary termination of pregnancy]. / Interruption volontaire de la grossesse.

PIP: The experience acquired in the 5 years since the legalization of abortion in France in 1975, allows an evaluation of the present situation. The French Academy of Medicine has always assumed a pronatalist position, and was instrumental in having the clause about consciencious objection passed into the law. A beneficial result of the law was an improvement in the technical conditions in which abortions took place, and a decrease in the incidence of illegal abortions. Negative results were the degradation of the notion of human life, the equation of a situation of distress with a situation of pure convenience, and a negative influence on the demographic situation of the country. Moreover, the 10 days' interval required by law between demand for abortion and the intervention itself, which was intended to provoke some serious reflection in a woman, is very often not respected, and the woman is straightforwardly encouraged to undergo abortion. The law legalizing abortion in France should be kept, but with serious modifications of a social, juridical, political, and material order.^ieng

[Malignant cyto-trophoblastic tumors following the abortion of a mole. Their treatment with methotrexate alone or in conjunction with surgery].

We report six case histories of malignant tumours following abortion of moles. In three cases their surgical removal allowed us to control them by histology: two of these were destruens chorio-adenomata, one case only was a choriocarcinoma. In the three other cases the cure was obtained by the sole use of anti-mitotic drugs. This treatment was undertaken on bioclinical evidence of malignancy which is certainly not foolproof, but which is practical in use, when one appreciates how difficult it is to diagnose some of these post-mole tumours histologically. There is a place for the surgical treatment of these cases in spite of the usefulness of Methotrexate. This place varies according to the age of the patients and the resistance of the tumours to treatment with anti-mitotic drugs.

[Clinical study of a new estro-progestative combination containing 2 mg of norethisterone acetate and 50 micrograms of ethinyl estradiol]. / Etude clinique d'une nouvelle association oestro-progestative contenant 2 mg d'acétate de noréthistérone et 50 microgrammes d'éthinyloestradiol.

PIP: The new low dose oral contraceptive SH 973 (Gynovlane, Schering), containing 50 mcg ethinylestradiol and 2 mg norethisterone acetate, was administered to 134 women for a variety of gynecologic indications. The most common indications were: contraception, 60 cases; ovarian cyst, 18; dysmenorrhea, 16; functional bleeding, 15; and endometriosis, 9. Treatment totaled 636 cycles, ranging from 1 to 11 cycles per patient, most often 3 cycles. All treatments were successful except in 2 women with ovarian cysts, 3 with functional bleeding, and 1 of 3 with hypoplastic uterus. There were no pregnancies or thromboembolic, psychiatric, or diabetic complications. Side effects included increased blood pressure in 5%, decreased in 6%, weight gain in 9.7%, bleeding in 8%, amenorrhea in 3.7%, leg pain in 3%, and breast congestion in 5%.^ieng