Comparison of two policies for induction of labour postdates.

The objective of this study was to compare maternal and midwifery manpower effects of policies for induction of labour (IOL) postdates, using a retrospective cohort design, in a level two maternity unit in a district hospital in South-West England. Primary outcome measures included mode of delivery, admission-delivery interval, midwifery manpower use. Group I consisted of 124 women who underwent IOL at 40+10. Group II were 104 women who underwent IOL at 42 weeks' gestation and 123 women who laboured spontaneously between 40+10 and 42 weeks' gestation. The nulliparous women had a shorter admission-delivery interval when induction was planned for 42 weeks, compared with 40+10 (p = 0.003), and required less frequent use of syntocinon (p = 0.04) and of continuous fetal monitoring (p = 0.02). The caesarean rate was higher in Group I than in Group II (p = 0.04) for nulliparous women only. The earlier induction policy was associated with a higher midwifery manpower requirement for nulliparae (p = 0.002). For parous women, the only difference was the greater use of oxytocin in labour. There was no difference between the groups in duration of labour, analgesia, Apgar scores, admission to neonatal care and meconium aspiration. In conclusion, delaying planned induction by three days was associated with lower medicalisation of labour and manpower needs for nulliparous women.

Unusual presentation of 22-kilogram retroperitoneal müllerian serous cystadenoma.

BACKGROUND: Müllerian cyst of the retroperitoneum is an extremely rare disease that is thought to be a subtype of urogenital cyst. It is a benign condition that can only be diagnosed and cured by surgical resection. CASE: An 80-year-old female with a huge cystic swelling, thought to be ovarian in origin, underwent laparotomy. Surgical exploration and subsequent histopathological analysis of the cyst revealed a müllerian serous cystadenoma of the retroperitoneum, 22 kg in weight. Preoperative ultrasound scan and computed tomography failed to elucidate a correct preoperative etiology. CONCLUSION: Huge retroperitoneal cysts may coexist with other pelvic pathology creating diagnostic and therapeutic dilemmas. The use of computed tomography for diagnosis may be not helpful with huge cysts. Good preoperative preparation and surgical technique are essential for managing these cases.

Contraceptive vaccine development.

Recent advances in antigen definition and production have made the development of a contraceptive vaccine more attainable. Such a vaccine must evoke an immune response that blocks an indispensable step in the reproductive process. Vaccine research involves many approaches to fertility prevention. Vaccines are being developed that could interrupt fertility by inhibition of gonadotrophin release, the function of follicle-stimulating hormone or the effects of human chorionic gonadotrophin (hCG); alternatively, they may prevent fertilization by interfering with the transport of spermatozoa or with sperm-zona pellucida binding. The most advanced prototype is a vaccine based on antibodies to beta hCG. Such vaccines are being studied for clinical efficacy. Many hurdles remain in contraceptive vaccine development. Since the antigens are peptides or small proteins, the resultant immune response is usually moderate, and better adjuvants and delivery systems must be developed to enhance and maintain the immune response. Improvement of the mucosal immune response may be necessary for vaccines incorporating sperm antigens. Research on vaccines that control fertility has resulted in a fascinating base of scientific knowledge that, it is hoped, can be converted into products that will allow another option for individuals who wish to control their fertility.

PIP: A contraceptive vaccine must stimulate an immune response that suppresses a crucial step in the reproductive process. The most advanced prototype vaccines are based on antibodies to beta-human chorionic gonadotropin. Other contraceptive vaccines in development are those based on gonadotropin-releasing hormone and on follicle-stimulating hormone. Gamete vaccines interfere with sperm transport or with sperm-zona pellucida binding. Contraceptive vaccine research in the US has focused on gamete antigens and on reproductive hormones. In contraceptive vaccine development research, the antigens tend to only cause a moderate immune response because they are peptides or small proteins. Improved adjuvants and delivery systems are needed to boost the immune response. Genetic engineering has allowed researchers to synthesize antigens and express them in vectors that ease the initiation of the immune response. Some possible vectors are BCG, Salmonella, vaccinia, and adenovirus. Direct placement of sperm antigens in the reproductive tract tends to elicit a poor mucosal immune response. More research is needed to find ways to improve the mucosal immune response for vaccines incorporating sperm antigens. Past and recent contraceptive vaccine research has formed a good scientific knowledge base. It is hoped that this base can lead to contraceptive vaccines.

Blood pressure variability and urinary electrolyte excretion in normotensive adults.

The principal aim of the present study was to determine the relationship of ambulatory blood pressure (BP) to urinary electrolyte excretion in normotensives. Twenty-five young adults underwent ambulatory BP and heart rate monitoring while collecting urine over 24 h. The correlations of 24 h urine sodium excretion and the ratio of sodium/potassium excretion with systolic BP in the laboratory (r = 0.12 and 0.24), ambulatory awake (r = 0.11 and 0.24), and ambulatory asleep (r = 0.24 and 0.31) settings were all in the positive direction but not significant. However, 24 h sodium excretion did correlate significantly and positively with awake and asleep ambulatory systolic (r = 0.45 and 0.41, P < .05) and diastolic (r = 0.42 and 0.43, P < .05) coefficients of variability. Thus, in normotensives on an unlimited diet, 24 h urinary sodium was more closely related to ambulatory BP variability than to BP level.

Developments in male contraception.

PIP: Relevant research efforts in male contraception involve: 1) hormonal approaches to block sperm production by inhibiting the hypothalamic-pituitary-gonadal axis, 2) disruption of sperm production by drugs that act directly on the testes, 3) interruption of sperm transport, and 4) alteration of secretions of the accessory sex glands and their subsequent effect on the spermatozoa. Both agonistic and antagonistic synthetic analogs of the hypothalamic gonadotropin releasing hormone (GnRH) factor cost too much and lack an effective mode of administration. Recent studies indicate that over 90% of Chinese and Indonesian men can develop complete azoospermia following either a testosterone or a progestin and an androgen combination treatment. Vaccines that utilize GnRH and follicle stimulating hormone as the active antigens have been introduced in clinical studies in the US and India. Drugs such as sulfasalazine, pyrimethamine, nitrofurane, and bis(di-chloracytal) diamines reduce male fertility but side effects make them unacceptable. Dinitropyrroles, halopropanedils, chlorosugars, and indazole carboxylic acids have been tried in laboratory animals. Gossypol rendered men infertile in large-scale clinical studies conducted in China but synthesis of safer analogs has not succeeded. Extracts of another plant, tripterigium wilfordii, are used in China as a popular herbal medicine. Vasectomy has improved with no-scalpel vasectomy and by the novel technique of blocking the vas with cured in situ polymeric plugs. Preliminary data suggest that men prefer condoms made from polyurethane as opposed to latex rubber increasingly used to protect against AIDs and sexually transmitted diseases. The antifungal agents, imidazoles, have spermicidal activity and synthetic variants may reduce undesirable side effects. Research on male-oriented methods has intensified during the last 10-15 years, but a new product is not likely to appear in the next 5-10 years.^ieng

Catheter occlusion of a mycotic renal artery aneurysm with cure of associated renovascular hypertension.

We describe successful transcatheter occlusion of a mycotic renal artery aneurysm. The patient's hypertension resolved following occlusion of the aneurysm and infarction of the renal parenchyma in the distribution of the aneurysmal vessel.

Intrinsic sympathomimetic activity counteracts beta-blocker inhibition of renin activation.

Enzymatically inactive renin (IR) is the predominant circulating form of renin. Sympathetic activity may influence plasma renin activity (PRA) by regulation of the conversion of IR to active renin (AR, PRA). It has been demonstrated previously that beta blockade lowers PRA at least partly through inhibition of this conversion process. The authors hypothesized that beta blockade and intrinsic sympathomimetic activity (ISA) would have opposing effects on production of AR from its inactive precursor. Eighteen primary hypertensives (12 male, 6 female, mean age 57.7 +/- 2.7) were entered in a placebo-controlled, double-blind crossover study of the effects of equipotent doses of pindolol and propranolol on mean +/- SEM systolic BP, diastolic BP, heart rate, active renin (AR), total renin (TR), inactive renin (IR), and % AR/TR. Drug dose was titrated to achieve a goal DBP of 90 mmHg or less. Active renin was defined as the rate of generation of angiotensin I in 37 degrees C plasma at pH 5.7. Total renin was determined by preincubation of plasma aliquots with 1.5 mg/mL trypsin in the presence of 5 mM benzamadine for one hour at -4 degrees C prior to assay of renin activity. Inactive renin was calculated as TR minus AR. The BP responses achieve by dose titration of propranolol and pindolol were virtually identical at rest, indicating equivalent depressor effects of the two beta blockers. Heart rate and active renin were, however, lowered to a much greater extent with propranolol as compared with pindolol. The lack of significant pindolol-induced fall in % AR/TR suggests that this drug has little net effect on the formation of AR from IR.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship of plasma renin activity to clinic and ambulatory blood pressure in elderly people with isolated systolic hypertension.

Eighty-one untreated elderly patients with clinic-defined isolated systolic hypertension (ISH) and 39 normotensive elderly subjects underwent 24-h ambulatory blood pressure monitoring. Before the ambulatory blood pressure monitoring, EDTA-anticoagulated venous blood was obtained from seated subjects for determination of plasma renin activity. Ambulatory blood pressure and heart rates were determined at 15-30-min intervals by a validated, portable non-invasive technique (Spacelabs 5200). Ambulatory blood pressure variability was defined for each subject as the standard deviation and the coefficient of variation of the ambulatory blood pressure. The mean awake systolic blood pressure was much lower than the clinic-determined value in the ISH group (P less than 0.001), but only slightly so in the normotensive group. Forty-two per cent of the clinic-defined ISH group had mean awake ambulatory systolic blood pressures below the 90th percentile of the normotensive group. A discrepancy between office and ambulatory blood pressures was not associated with blood pressure variability, heart rate or plasma renin activity.

Comparison of office, home and 24-hour ambulatory blood pressures in borderline and mild hypertension.

Clinic/office (casual), home (self), and twenty-four-hour ambulatory (ABP) blood pressure determinations were compared in 32 subjects defined by conventional office criteria as mild or borderline hypertensives. Office diastolic blood pressures (mean 93.1 +/- 5.3 mmHg) were significantly higher than either home (mean 88.9 +/- 7.1 mm Hg) or awake ABP (mean 88.4 +/- 8.4 mm Hg) readings for the total group, as well as for the mild hypertension subgroup (office mean 96.0 +/- 3.5 mm Hg, home mean 91.0 +/- 8.0, awake ABP mean 90.4 +/- 8.8) but not for the borderline subgroup. In the total study group, office diastolic blood pressure (DBP) correlated better with home DBP (r = 0.58, p = 0.0005), than with the awake ABP (r = 0.40, p = 0.02). Home DBP correlated well with awake DBP (r = 0.48, p = 0.006). In subgroup analysis, office DBPs correlated well with home (self) readings for both the mild (r = 0.53, p = 0.03) and the borderline (r = 0.62, p = 0.01) subgroups. When office DBPs were compared with awake ABP DBPs, the correlation coefficient for the mild subgroup was significant (r = 0.49, p = 0.04); this was not the case for the borderline subgroup (r = 0.10, p = NS). Comparison of home (self) DBPs with awake ABP determinations revealed a good correlation for the borderline subgroup (r = 0.63, p = 0.01) but not for the mild subgroup (r = 0.35, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative anti-fertility effects of gossypol enantiomers in male hamsters.

The enantiomers of gossypol have been tested as male oral anti-fertility agents in hamsters. As determined by fertility tests the (-) isomer was fully active at half the effective dose of the racemate, whereas the (+) isomer exerted no anti-fertility effect.

Digoxin-like immunoreactive substance in chronic hemodialysis patients: effect on digitoxin radioimmunoassay.

Digoxin-like immunoreactive substance(s) (DLIS) in the sera of patients with renal insufficiency may confound attempts to monitor serum digoxin levels. We investigated whether DLIS would affect the radioimmunoassay (RIA) for digitoxin. DLIS was detected by RIA in 9 of 38 chronic hemodialysis patients and in none of 25 healthy controls. Digitoxin levels were not elevated in either the control or dialysis group, and false-positive results for digitoxin by RIA were not obtained in any patient with DLIS. It is concluded that DLIS does not interfere with the digitoxin RIA, nor are digitoxin levels spuriously elevated in chronic hemodialysis patients. Digitoxin may be a preferable preparation for digitalis-dependent dialysis patients with DLIS.

The effect of dialysate calcium levels on blood pressure during hemodialysis.

A controlled double-blind prospective study was undertaken of the effect of dialysate calcium levels on BP during hemodialysis. Twenty patients and 240 dialyses were studied using a protocol in which patients underwent alternate hemodialyses with dialysate calcium of 2.5 and 3.5 mEq/L. Dialysate composition was otherwise the same. Mean BPs during dialysis were significantly lower at 1.5, 2.5, and 3.5 hours of dialysis when the lower dialysate calcium was used (P = .007 to .02). However, the difference in BP between the high and low dialysate calcium treatments was clinically minor, with a maximum mean difference (at 1.5 hours) of 4.6 mm Hg. Subgroups of patients with frequent hypotension and low or normal serum calcium did not appear more sensitive to the hypotensive effect of low calcium dialysate. Dialysate calcium levels of 2.5 and 3.5 mEq/L thus differ in their effect on intradialytic BP in a statistically significant, but clinically minor, way. Low calcium dialysate thus may prove useful in the management of patients in whom large amounts of enteric calcium absorption are indicated or unavoidable.

(-)-Gossypol: an active male antifertility agent.

The enantiomers of gossypol have been resolved by preparative HPLC of diastereomeric Schiff's base derivatives on a chiral bonded phase. Whereas (+)-gossypol has previously been reported to be inactive, (-)-gossypol is now shown to be active as a male oral antifertility agent in hamsters.

PIP: This paper describes the successful separation of (-)-gossypol from the racemate and demonstrates that in hamsters, it is indeed the component possessing male oral antifertility activity. Young, adult male hamsters were randomly divided into 4 groups of 5, and were treated with the agent orally, once a day, for 40 days. Each male was cohabited with a new set of 2 adult, virgin females for 1 week and the females, in turn, were checked daily for the presence of sperm in the vagina. After 37 days of treatment with (-)-gossypol, only 2 out of 5 males were fertile, and a further loss of fertility was apparent during the next cohabitation period. Results show that gossypol-acetic acid is more effective in reducing fertility at a dose level of 16 mg/kg/day than either of the other drugs tested. However, it is also shown to be more toxic as expressed by reduced body weight gain of the hamsters tested. Overall, based on the limited dosing schedule employed, the minus isomer appears about twice as potent as the racemic mixture.

Long-acting contraceptive agents: structure activity relationships in a series of norethisterone and levonorgestrel esters.

A large number of esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) and levonorgestrel (D-(-)-13 beta-ethyl-17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one) were synthesized and tested for biological activity. The test employed in these studies was the duration of estrus suppression in cycling mature rats. In the norethisterone series several esters exhibited duration of activity comparable to that of norethisterone enanthate. In the levonorgestrel series the butanoic, cyclobutylcarboxylic and cyclopropylcarboxylic esters were longer acting than medroxyprogesterone acetate (17 alpha-acetoxy-6 alpha-methylpregn-4-ene-3,20-dione) when prepared as aqueous microcrystalline suspensions.

PIP: A large number of esters of norethisterone (17alpha-ethynyl-17beta-hydroxyestr-4-en-3-one) and levonorgestrel (D-(-)-13beta-ethyl-17alpha-ethynyl-17beta-hydroxygon-4-en-3-one) were synthesized and tested for biological activity. The test employed in these studies was the duration of estrus suppression in cycling in mature rats. In the norethisterone series, several esters exhibited duration of activity comparable to that of norethisterone enanthate. In the levonorgestrel series, the butanoic, cyclobutylcarboxylic, and cyclopropylcarboxylic esters were longer acting than medroxyprogesterone acetate (17alpha-acetoxy-6alpha-methylpregn-4-ene-3,20-dione) when prepared as aqueous microcrystalline suspensions.

Potential antifertility agents. 6. Synthesis and biological activities of optical isomers of 4 beta-(p-methozyphenyl)-2 beta-methylcyclohexane-alpha-carboxylic acid and related compounds.

PIP: The optical isomers of the title compound were synthesized and the biological potencies of the two enantiomers were compared. There was essentially no difference in their hypocholesterolemic activities, as had been predicted, and little or no difference between their uterotropic potencies. The approximately equal uterotropic activities seen with the enantiomers is explained in terms of stereochemical requirements at the receptor level for an estrogenic response. A working model of an estrogenic receptor is proposed. An accompanying paper provides support for the proposed model.^ieng