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All patients hospitalized in 1982 at the Department of Gynecology in Malmö because of malignancy of the cervix uteri attended an interview study concerning the presence of cervical cancer among their nearest relatives. In addition, these patients were questioned concerning earlier gonorrheal infection. The blood group was determined as also was the secretory status and Gm allotype. As a control group the families of the male consorts were used. Cervical cancer was found significantly more often in mothers of the patients (7.9%) than in the consorts' mothers (1.0%). Sisters, aged 20 or over, of the patients had cervical cancer significantly more often (7.5%) than sisters of the consorts (1.1%). Moreover, cervical cancer in mothers and/or sisters was found in 15.6% of the patients. In cases of invasive cancer or previously operated CIS, this figure was 17.5%. The patients did not differ significantly from the normal population regarding blood group or secretory status. A somewhat lower, although non-significant, frequency of Gm(1) allotype was found in patients with invasive cancer, compared with patients with CIS. Patients with a positive family history of cancer had more often had gonorrhea (24%) than patients with a negative family history (18%). The study indicates a multifactorial etiology for cervical cancer.

A new gel-formulation for intracervical application of prostaglandin E2 (PGE2) has been prepared. As a vehicle for the gel a cross-link starch polymer is used. PGE2 substance is added to the starch polymer and after homogenization and lyophilization a PGE2 powder is obtained. The powder can be stored at room temperature for more than four months without inactivation of the prostaglandin. Before clinical application a few ml of saline is added to the powder giving, within 30 seconds, an easily-handled ready to use PGE2-gel. Chemical analysis by spectrophotometric technique reveals that the amount of unchanged PGE2 is the same in the new gel-formulation as in a conventional cellulose gel. In a randomized double-blind study the new PGE2-gel was intracervically applied to twenty nulliparae before abortion by dilatation and evacuation (D & E). Ten women were given a gel containing 0.25 mg PGE2 (PGE2-gel) and ten a gel without PGE2 (placebo gel). It was found that the PGE2-gel, in contrast to the placebo gel, produced a rapid ripening of the cervix facilitating the subsequent D & E. No adverse systemic or local reactions were found during or after the treatment.

Eight primigravid women with a mean gestational age of 9.4 weeks (9 to 10 weeks) who were admitted for first-trimester abortion by dilatation and evacuation were preoperatively treated for 6 hours with either intravenous infusion of oxytocin or a strictly intracervical application of prostaglandin E2 (PGE2) in viscous gel. Myometrial activity was monitored by intrauterine pressure recording throughout the treatment. Contractile activity was more pronounced in the oxytocin-treated group, whereas cervical priming occurred after the PGE2 treatment only. Intracervical PGE2-gel is suggested to have direct effects on the cervical tissues, independent of uterine contractile activity. Furthermore, myometrial stimulation induced by escape of gel into the extra-amniotic space can be avoided by adjusting the volume of gel and technique of application to the dimensions of the cervix.

One hundred nulliparas at term were randomly given oxytocin intravenously or prostaglandin E2 (PGE2) gel (0.5 mg PGE2) intracervically in order to study the effect on cervical ripening and the frequency of successful inductions. In the presence of a favorable cervix both methods seemed equally efficacious in inducing labor. However, when the cervix was unfavorable, 53% of the patients could be delivered with PGE2 gel, compared with 31% when oxytocin was given. In patients with a highly unfavorable cervix this difference was significant (P less than 0.02). In patients not induced into labor, PGE2 gel caused a considerable ripening of the cervix, with a change in Bishop score from 2.9 to 6.3. In patients undelivered after oxytocin stimulation, no change in Bishop score occurred. This effect of locally applied PGE2 gel on cervical ripening was highly significant (P less than 0.001). No adverse maternal or perinatal effects were observed, irrespective of the mode of treatment.

From 18 apparently healthy women wearing a copper-IUD, endometrial biopsy specimens were obtained under hysteroscopic control, both from the site of the IUD and from a distant area. The fibrinolytic activity proved significantly higher in the former specimens than in the latter. The results provide a theoretical basis for the development of an IUD which releases a synthetic inhibitor of fibrinolysis.

The effects of the calcium antagonist, nifedipine, on uterine activity induced by prostaglandins F2 alpha (PGF2 alpha) and E2 (PGE2) were studied in women undergoing therapeutic midtrimester abortion, and in patients with a missed abortion in the 16th to 27th week of pregnancy. In the five subjects receiving intra-amniotic PGF2 alpha (25 to 40 mg) for midtrimester abortion, nifedipine (30 mg orally) decreased uterine activity from a mean of 372 to 203 Montevideo Units. The effect on the intensity of the contractions was pronounced; frequently and basal tone were little affected. In patients with missed abortion, uterine contractions were induced by extra-amniotic application of PGE2 (0.5 to 1.5 mg) in a viscous gel. The activity was often more irregular than that in the women receiving intra-amniotic PGF2 alpha. However, nifedipine (30 mg orally) had a marked inhibitory effect on the uterine contractions. It is concluded that nifedipine can be used for treatment of uterine hyperactivity induced by prostaglandins. Combined treatment with beta 2-adrenoceptor stimulants might be considered.

Prostaglandin E2 (PGE2) suspended in a viscous gel was deposited intracervically to 115 patients at term with an unripe cervix. 45 of these patients were given a single dose of 1.0 mg PGE2, whereas the remaining 70 received only half that dose, i.e. 0.5 mg. Irrespective of dose greater than 60 per cent of the patients were induced into labor and delivered without further stimulation within less than 24 hours. The mean induction delivery time was 10 hours. In the remaining patients a considerable ripening of the cervix was registered. Hypercontractility did occur in one patient given 1.0 mg PGE2, otherwise no maternal side effects were observed. There were no adverse effects on the fetuses. The number of instrumental deliveries was 19 per cent including 9 per cent cesarean sections. It is concluded that locally applied PGE2-gel can be used to produce ripening of the cervix and/or induce labor in patients at term with an unripe cervix. Since there was practically no difference in efficiency between the two doses but one case of hyperstimulation in patients given 1.0 mg PGE2, the smaller dose, i.e. 0.5 mg is recommended.

16 patients were treated with the fibrinolytic inhibitor tranexamic acid in an initial i.v. dose of 1 g followed by an oral dose of 4 g a day for one week and 3 g a day for two weeks. Biopsy specimens of superficial veins were obtained before and on the last day of treatment and examined histochemically for their fibrinolytic activity. Tranexamic acid did not suppress the fibrinolytic activity in the vessel walls, which is the most important link in the fibrinolytic defence system against thrombosis.

In a randomized double-blind study a viscous gel, containing 0.25 mg prostaglandin E2 (PGE2-gel) or without prostaglandin (placebo gel), was applied intracervically in twenty-two nulliparous patients just before termination of early pregnancy by dilatation and evacuation (D & E). Within twelve hours a marked ripening of the cervix was found in all the eleven patients receiving PGE2-gel. Thus, a significant change in cervical dilatation from mean 5.4 mm to mean 10.7 mm occurred. Furthermore, a considerable softening of the cervix was registered. In the eleven patients receiving placebo gel, no significant changes in cervical dilatation or consistency were found. The subsequent D & E was easily performed in all patients treated with PGE2-gel. However, in three of the patients given placebo gel, D & E was difficult to carry out because of an unfavorable cervical state. To eliminate or decrease myometrial activity the calcium antagonist nifedipine was given orally to eight patients at application and five hours after application of 0.25 mg PGE2-gel. None of the patients recognized uterine contractions. However, also in these patients significant changes in cervical consistency and dilatation occurred within twelve hours. No side effects of the treatment were observed. It is concluded, that a preoperative, intracervical single application of 0.25 mg PGE2 seems to be useful to ripen the unfavorable cervix before subsequent termination of early pregnancy by D & E.

To terminate pregnancy 15 women with an established diagnosis of missed abortion or intrauterine dead fetuses were treated with 1.0 mg Prostaglandin E 2 in viscous gel applied as a single intracervical dose. -- Abortion was induced after a mean of 7.0 hours in 8 patients with a mean gestational age of 15.0 weeks, and a subsequent evacuation of the uterine cavity was easily performed. -- Complete abortion/delivery was obtained in 7 patients with a gestational age of 33 weeks. The over-all mean induction/delivery time was 7.5 hours. -- Apart from pain related to uterine contractions no side effects were observed and no complications occurred. It is concluded that the present technique represents a promising alternative in the treatment of patients with missed abortion or intrauterine dead fetuses.

A survey of connective tissue in general and human cervical connective in particular is presented. It is concluded that about 90% of the human cervix consists of fibrous connective tissue which, according to the composition of the collagen and the proteoglycans, is very similar to that in skin and sclera. The high activity of collagenase probably gives the cervical connective tissue from pregnant women its potential to ripen following prostaglandin treatment. Electron microscopical examination has revealed an increased amount of amorphous substance after such treatment. This may be caused partly by degraded collagen fibers and partly by newly synthesized proteoglycans.