Slit ventricle syndrome with aqueduct stenosis: third ventriculostomy as definitive treatment.

Slit ventricle syndrome is a poorly understood entity characterized by features of raised intracranial pressure and small ventricles in shunt-dependent hydrocephalics. Five patients with this syndrome were treated with antisiphon devices, high pressure shunts, or subtemporal decompression, but continued to be symptomatic. Third ventriculostomy, performed as a last resort in these patients, gave encouraging results. The patient data, operative approach, and preliminary results are presented here.

A novel presentation of Coxsackie B2 virus infection during pregnancy.

A 39-year-old woman presented at 34 weeks gestation with a febrile illness. This initially settled but recurred 6 days later, when uncontrolled vaginal bleeding necessitated caesarian section. At operation, vesicles were seen on the mother's hyperaemic uterus. The infant developed tachypnoea, bradycardia, cerebral irritation, an enlarged liver and spleen, intravascular coagulation and a transient rash. Mother and child made a full recovery. Coxsackie B2 virus was isolated from the infant and rises in the titre of Coxsackie B virus-specific IgM were detected in mother and child.

Early termination of pregnancy: medical induction with prostaglandins versus surgical aspiration under local anesthetic.

Termination of pregnancy at 4-8 weeks gestation in 1085 patients using either local prostaglandin instillation (n = 820) or uterine aspiration under local anesthetic (n = 265) have been analyzed. Morbidity for both methods was similar although the incidence of side-effects (0.4%) and the transfusion rate (0%) were lower after aspiration than the respective rates of 59% and 1.3% after prostaglandin treatment. However the rates of genital tract trauma (0.75%) and uterine sepsis (1.8%) after aspiration were higher than the respective rates of 0.3% and 0.9% after prostaglandin treatment. The major disadvantage of prostaglandin treatment was the rate of re-admission for evacuation (8.5%) compared with (0.9%) after aspiration, although patient acceptability for both techniques was similar. In view of the advantages, more widespread use of both methods of termination is indicated.

Mid-trimester termination of pregnancy with 16,16-dimethyl-trans-delta 2 PGE1 vaginal pessaries: a comparison with intra- and extra-amniotic prostaglandin E2 administration.

PGE1 analogue (gemeprost) vaginal pessaries administered three hourly for three doses has been compared with a single extra- or intra-amniotic injection of PGE2 for mid-trimester termination of pregnancy in 450 women between 13 and 20 weeks gestation. The mean (SD) induction-abortion interval (IAI) in the vaginal pessary group of 19.5 (8.4) h was significantly longer than the respective intervals of 14.4 (9.3) and 16.1 (6.8) h in the patients treated extra- or intra-amniotically (P less than 0.001). Seventy-three percent treated with gemeprost aborted within 24 h of initial treatment compared with 84% and 87%, respectively in the extra- and intra-amniotic groups (P less than 0.05). Patients treated with gemeprost were more likely to need further prostaglandin treatment and had an increased incidence of gastrointestinal side effects. Despite these differences vaginal gemeprost pessaries provide a safe, effective, easy to administer method for midtrimester termination of pregnancy.

Laparoscopic laser sterilisation: an alternative option.

The aim of this prospective study was to evaluate the safety and efficacy of female laparoscopic laser tubal sterilisation. A total of 265 women underwent laparoscopic laser sterilisation as a day-case procedure at Princess Royal University Hospital in Kent between 1996 and 2001. The fallopian tube was divided at the isthmic portion using a neodymium-yttrium aluminium garnet (Nd:YAG) laser probe. All procedures were completed laparoscopically and patients were discharged within 6 h of surgery. No perioperative complications were encountered. The mean follow-up duration was 36 months (range 2 - 7 years) and no intra- or extrauterine pregnancies were reported throughout the entire follow-up period. We conclude that laparoscopic Nd:YAG laser sterilisation appears to be a safe and effective day-case method of female sterilisation. Larger studies with longer follow-up are needed to further define its role as a reliable long-term contraceptive method.

Safety of the Helica Thermal Coagulator in treatment of early stage endometriosis.

The objective of this prospective study was to assess the safety and short-term outcome of the Helica Thermal Coagulator in the laparoscopic treatment of early stage endometriosis. Two hundred and fifty consecutive women with chronic pelvic pain and stage I and II endometriosis (r-AFS classification) were treated laparoscopically with the Helica Thermal Coagulator. No bladder, ureteric or bowel injuries occurred. None of the procedures was converted to laparotomy and there were no major peri-operative complications. The only complication was a vaginal perforation during dissection of the cul-de-sac in a patient with a vaginal vault endometriotic nodule. We conclude that the Helica Thermal Coagulator is a safe alternative for the treatment of mild to moderate endometriosis. Long-term efficacy studies are required to better assess the role of the device in laparoscopic management of endometriosis.

2308 second trimester terminations using extra-amniotic or intra-amniotic prostaglandin E2: an analysis of efficacy and complications.

A total of 2308 mid-trimester terminations using PGE2 extra-amniotically (1608) or intra-amniotically (700) has been analysed for efficacy and immediate and early morbidity. The mean induction-to-abortion intervals were similar for the two routes. Overall, 67% of the patients were in hospital for 1 night. Morbidity rates were similar for the two administration routes and were no higher than those reported for second trimester terminations using dilatation and evacuation. Minor side-effects of vomiting occurred in 1006 (44%) and diarrhoea in 320 (14%). Forty (1.7%) lost more than 500 ml of blood during termination and 13 (0.6%) were transfused. Major complications were extremely rare and genital tract trauma only occurred in 4 (0.17%) and proven pelvic infection in 2 (0.08%) patients. Thirty-three (1.4%) were readmitted and required a surgical evacuation of the uterus. Since long-term complications have been assessed for this method of termination and found to be infrequent, we see no reason to consider a change in methods for second trimester terminations.

The aetiology of vaginal bleeding in children. A 20-year review.

The cause of vaginal bleeding in girls of 10 years and under is reviewed. Of the 52 patients seen, in 28 (54%) bleeding was caused by a local lesion and 11 (21%) of these had malignant genital tumours. Eleven (21%) children presented with some form of precocious puberty, and in 13 (25%) patients no cause could be found.

The efficacy of oral Mifepristone (RU 38,486) with a prostaglandin E1 analog vaginal pessary for the termination of early pregnancy: complications and patient acceptability.

Outpatient terminations were performed on 100 ultrasonographically confirmed pregnancies of less than or equal to 63 days with a single oral dose of RU 38,486 (600 mg) and a single vaginal pessary of 16,16-dimethyl-trans-delta 2-prostaglandin E1 (1 mg) 48 hours later. Abortion occurred in all patients; in 95 it was complete, in four it was incomplete, and one resulted in a missed abortion. In 88% the abortion occurred within 4 hours of prostaglandin treatment. A total of 25% of patients had nausea and 15% vomited after RU 38,486 treatment. After prostaglandin-treatment, 13% vomited, 10% had diarrhea, and 23% required administration of an opiate analgesic agent. No patient was transfused and there was no genital tract trauma; one case of suspected pelvic infection occurred. If the need for termination arose again, 88% would elect to use the method again, 9% would not. The combination of the antiprogestin RU 38,486 and a vaginal prostaglandin pessary appears to offer a safe, efficient, acceptable nonsurgical outpatient method of termination. Further studies on dosage and treatment protocols would be justified.

Transplacental passage of mifepristone and its influence on maternal and fetal steroid concentrations in the second trimester of pregnancy.

The maternal and fetal endocrine effects of the maternal administration of the anti-progestin mifepristone in mid-pregnancy have been investigated. Mifepristone and the metabolite RU 42,633 were detected in the fetal circulation and in the amniotic fluid 4, 24 and 48 h after oral ingestion. Maximum fetal plasma concentrations of mifepristone occurred 4 h after treatment indicating rapid placental transfer of the drug. No significant changes in progesterone, cortisol, oestradiol or aldosterone concentrations were detected in the maternal circulation after mifepristone treatment. No significant changes occurred in the fetal progesterone, oestradiol or cortisol concentrations, but a significant increase in fetal aldosterone occurred 4 and 24 h after treatment. The significance of these results is discussed in relation to the possible therapeutic uses of mifepristone for inducing labour.

PIP: Physicians gave 600 mg of oral mifepristone or an identical placebo to 12 patients of John Radcliffe Hospital, Oxford, England for a 2nd trimester abortion (16-19 weeks gestation) by prostaglandin injection. They took fetal blood samples 4 hours after tablet ingestion. They gave the same dosage of mifepristone to 12 similar women, but took fetal blood samples at 24 or 48 hours post treatment. The physicians wanted to determine placental transfer of mifepristone and its metabolite RU 42,633 and their effects on maternal and fetal plasma steroid concentrations. Maternal mifepristone levels were 10-15% and maternal RU 42,633 levels were 6-12% higher than fetal levels regardless of time intervals. The highest maternal plasma mifepristone (2.7 mcmol/1) and RU 42,633 (3.6 mcmol/1) levels and the highest fetal plasma mifepristone level (0.32 mcmol/1) were at 4 hours post treatment. The highest fetal plasma RU 42,633 level was at 24 hours post treatment, however. Similarly amniotic levels of mifepristone and RU 42,633 were highest at 24 hours post treatment (0.33 mcmol/1 and 0.46 mcmol/1 respectively). Progesterone levels tended to be consistently higher in the fetal (703-4090 nmol/1) than the maternal circulation (85-228 nmol/1), but cortisol levels tended to be always higher in the maternal (425-1385 nmol/1) than the fetal circulation (24-117 nmol/1). The only significant difference between the mifepristone and placebo groups occurred in fetal aldosterone concentrations at 4 and 24 hours post treatment (p.05). They were higher in the mifepristone group than the placebo group (mean 1700 pmol/1 an 1458 pmol/1 vs. 999 pmol/1 respectively). These results showed that mifepristone and RU 42,633 crossed the placenta and were absorbed quickly. Since the induction abortion interval was about 40% lower in women taking mifepristone, it may be used therapeutically at term to induce labor.

The placental transfer of mifepristone (RU 486) during the second trimester and its influence upon maternal and fetal steroid concentrations.

A double-blind, placebo-controlled study has assessed the maternal and fetal endocrine effects of the maternal administration of the anti-progestin mifepristone in mid-pregnancy. There were six women in each group. Four hours after oral administration of 600 mg mifepristone, the drug was detected in both maternal and fetal circulations and in the amniotic fluid. No significant changes in progesterone, cortisol, oestradiol, or aldosterone concentrations were detected in the maternal circulation after treatment with mifepristone or placebo. In women treated with mifepristone, the mean fetal aldosterone level was 1699 (SD 217) pmol/l which was significantly higher than the mean level of 999 (SD 84) pmol/l in the control group but no significant changes occurred in the fetal progesterone, oestradiol or cortisol concentrations. The significance of these results is discussed in relation to the possible therapeutic uses of mifepristone for inducing labour.

PIP: The effects of RU 486, a competitive progesterone receptor antagonist, on maternal and fetal steroid concentrations were investigated in a double-blind study of 12 women in the 16th-19th weeks of pregnancy. The 6 study subjects received 600 mg of oral RU 486 on the day of abortion induction, while 6 controls received a placebo tablet. RU 486 was detected in maternal and fetal circulations and amniotic fluid 4 hours after administration to the 6 subjects, indicating that RU 486 and its metabolite, RU 42,6333, rapidly cross the placenta. There were no significant differences between cases and controls in terms of maternal progesterone, cortisol, estradiol, or aldosterone concentrations. In addition, fetal progesterone, estradiol, and cortisol concentrations did not differ between the RU 486 and placebo groups; however, fetal aldosterone levels were significantly higher in the treatment group (mean, 1699 pmol/l) than in controls (mean, 999 pmol/l). It is not known whether this unexpected f inding reflects the action of RU 486 blocking fetal mineralocorticoid receptors or was attributable to chance. Although more research is needed on the fetal endocrine effects of mifepristone, it appears that RU 486 has substantial potential for inducing labor in 2nd trimester abortion without serious drug-related side effects.

The effect of RU 38,486 on progesterone and oestrogen receptor concentrations in the decidua and placenta in early pregnancy.

Decidual and placental concentrations of progesterone and oestrogen receptors in 15 women having medical terminations of pregnancy with a combination of the anti-progesterone steroid RU 38,486 and prostaglandin E1 analogue have been compared with 10 matched controls undergoing surgical aspiration of pregnancy. In the patients treated with RU 38,486, the mean (SD) decidual cytosolic and total progesterone receptor concentrations of 4.3 (5.6) and 7.6 (7.1) fmol/microgram DNA respectively were significantly lower than the levels of 18.5 (14.4) and 22.3 (17.4) fmol/microgram DNA in the control patients. Progesterone receptor concentrations in the placenta were very low in both groups. No significant change in oestrogen receptor concentrations occurred in the decidua or placenta after treatment with RU 38,486. These data indicate that there may be down-regulation of decidual progesterone receptor concentrations following RU 38,486 treatment.

The physiological and clinical effects of progesterone inhibition with mifepristone (RU 486) in the second trimester.

A double-blind placebo-controlled trial was performed in 20 primigravidae to assess the physiological and clinical effects of oral mifepristone on myometrial contractility and sensitivity in the second trimester. Ten women received 600 mg of oral mifepristone and 10 women a placebo 24 h before abortion was induced in both groups, with extra-amniotic PGE2 instillation. Intrauterine pressure recordings demonstrated increased spontaneous uterine activity and increased sensitivity to PGE2 and ergometrine, but no change in oxytocin sensitivity after mifepristone treatment. There were no significant differences in PGE or PGF metabolite concentrations in peripheral maternal plasma over the 24-h study period after treatment between the mifepristone and placebo groups. The mean induction abortion interval in the mifepristone group was 512 (SD 321) min compared with 1128 (SD 606) min in the placebo group (P less than or equal to 0.02). The mechanism whereby mifepristone provokes enhanced uterine contractility and sensitivity to prostaglandins, with a reduction in abortion times, does not appear to be through endogenous production of PGE or PGF.

P29, an oestrogen receptor-associated protein, is down-regulated by mifepristone in first trimester human placenta and decidua.

P29 is an oestrogen receptor-associated protein which acts as a marker of oestrogen action in several systems. The concentration of P29 was measured in placenta and decidua from women following medical termination of pregnancy with the antiprogesterone steroid mifepristone (RU 38,486) and a prostaglandin E1 analogue, and compared with the concentration of P29 found in matched controls undergoing surgical aspiration of pregnancy. Oestrogen receptors were also measured in the same samples. Placental and decidual P29 concentrations (IU/mg protein) in patients treated with mifepristone were 9.6 (4.6-54) and 4.8 (1.3-13.3) (median and range), respectively. These values were significantly lower than the corresponding values, 39.5 (27-69) and 22.0 (2-107) in the surgical group. In contrast, the levels of oestrogen receptors did not change significantly in either decidua or placenta. These data show that mifepristone causes down-regulation of P29 in placenta and decidua, and therefore its action may disrupt oestrogen function in uterine tissues.

The effect of the anti-progestin mifepristone (RU 486) on plasma prostaglandin metabolite levels in early pregnancy and its influence on pregnancy termination.

The effect of a single dose of RU 486 (600mg) on prostaglandin metabolite levels has been studied over a 48 h period in 20 women undergoing medical termination of early pregnancy. The results were compared with controls of similar gestation who were treated surgically. The mean (SD) PGEM levels at 0 and 48 h in the RU 486 group were 13.7 (2.7) and 13.2 (2.2) pg/ml respectively, which was not significantly different from the values of 11.7 (1.1) and 11.3 (0.4) pg/ml measured in the control patients. Similarly the mean (SD) PGFM values of 22.3 (14.7) and 17.0 (7.2) pg/ml at 0 and 48 h were not significantly different from the corresponding control values of 21.9 (13.8) and 23.8 (7.2) pg/ml. In 10 of the study patients, there were no significant changes in PGEM and PGFM concentrations prior to and at 4, 24 and 48 h after RU 486 administration. Although all pregnancies were successfully terminated with the combination of RU 486 and subsequently a vaginal pessary containing PGE1, no stimulation of prostaglandin production could be demonstrated.

Temporal changes in the expression of the insulin-like growth factor II gene associated with tissue maturation in the human fetus.

The insulin-like growth factors are broadly distributed in the human conceptus and are thought to play a role in the growth and differentiation of tissues during development. Using in situ hybridization we have shown that a wide variety of specific cell types within tissues express the gene for insulin-like growth factor II at times of development from 18 days to 14 weeks of gestation. Examination of blastocysts produced by in vitro fertilization showed no expression, thus bracketing the time of first accumulation of IGF-II mRNA to between 5 and 18 days postfertilization. The pattern of IGF-II expression shows specific age-related differences in different tissues. In the kidney, for example, expression is found in the cells of the metanephric blastema which is dramatically reduced as the blastema differentiates. The reverse is also seen, and we have noted an increase in expression of IGF-II in the cytotrophoblast layer of the placenta with gestational age. The sites of expression do not correlate with areas of either high mitotic activity or specific types of differentiation, but the observed pattern of expression in the kidney, adrenal glands and liver suggests an explanation for the abnormally high IGF-II mRNA expression in developmental tumours such as Wilms' tumour.