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It is proposed that opening and closure of the proximal urethra and bladder neck are regulated by a battery of surrounding structures, the most important being the pubourethral-vesical ligaments, the suburethral vaginal wall, 'the hammock', the pubococcygeus muscles, the levator plate and the connective tissue which like glue connects these structures to each other. Inappropriate function in one of these structures can, to some extent, be compensated for by an improved function in another hereby maintaining continence. However, a significantly deteriorated function in the support of urethra--normally maintained by the pubourethral/pubovesical ligaments, the pubococcygeus muscles and suburethral vaginal wall--will result in pronounced stress incontinence. Severe defects in these structures can generally not be compensated for by exercises of the pelvic muscles. This is true, in particular, if there is also a defect function in the connective tissue which 'glues' the urogenital structures to each other. Under such circumstances surgical procedures have to be considered to alleviate the patients symptoms. What is said so far must not exclude the importance of recognizing the role of the internal urethral structures to maintain continence, in particular the quality of urethral muscles, connective tissue and vascularization. In some specific cases of mixed incontinence it can be speculated whether the urge symptom can be caused by an anatomical dysfunction causing the proximal urethra and the bladder neck to remain involuntarily open or to open promptly at even minor pressure provocations. If so distension of the bladder neck and proximal urethra may activate stretch receptors located here which will induce uninhibited detrusor contractions. The presence of estrogen receptors in many of the structures involved in preserving continence may explain the increased prevalence of dysfunctions in the urogenital tract in postmenopausal patients, in particular in those not on hormone replacement therapy.

The significance of cough transmission ratios (CTR) in 6 unoperated and 15 previously operated patients is discussed. It is concluded that CTR is an index of periurethral muscle contractile activity, and vaginal wall tension, rather than urethral closure.

Urinary incontinence was observed in 19 patients after bladder neck elevation or vaginal repair operations. Characteristically, patients could not suppress their urge to micturate on getting up in the morning, and they wet before arrival at the toilet. Urodynamically, a high posterior cough transmission ratio was noted. A 1.5 cm longitudinal incision in the vagina, dissected free and resutured horizontally (I-plasty), immediately cured this particular condition, but ultimately failed in 1/3 cases. Most of these failed patients were subsequently cured by further adjustment of vaginal tension under local anaesthesia (Tuck procedure). These findings confirm the emphasis given by the Integral Theory of Female Urinary Incontinence as to maintain adequate elasticity in the zone of critical elasticity (ZCE) of the supralevator vagina. The ZCE acts as an elastic hinge, allowing (i.e. facilitates) the separate and opposite contractile forces of anterior pubococcygeus, and levator plate which are necessary to close off urethra and bladder neck respectively. Inadequate elasticity at the ZCE converts the ZCE's role from facilitation to opposition. The stronger levator muscle contraction counteracts the forward section of the weaker anterior part of pubococcygeus muscle, preventing bladder neck closure.

Thirty patients with symptoms and signs of stress and urge incontinence were treated with a Combined Intravaginal Sling and Tuck procedure. Primarily, only the first part of the procedure, the Sling operation was undertaken. This procedure creates an artificial pubourethral ligament which is achieved by controlled deposition of collagen around a retropubically implanted, removable, 0.5 cm wide Mersilene tape, inserted through a special tunneler. This part, stage 1 of the combined surgical procedure is mainly performed under local anaesthesia without postoperative catheterization, and early return to work. Urgency symptoms were cured simultaneously with the stress symptoms. The 50% success rate of the sling procedure was improved to 82% when the second part (stage 2) of this operation was undertaken. This procedure, the "Tuck" operation, tightens the suburethral vagina. The results of the combined procedure indicate that both an intact pubourethral ligament and tight suburethral vagina are equally important for cure as proposed in the Integral Theory of Female Urinary Incontinence.

A new surgical principle which can safely result in the formation of an artificial neo-ligament, and induce the adhesion of tissues is described. Under certain conditions, an implanted Mersilene tape may act as a template, provoking a controlled linear deposition of collagen which remained unchanged, even after removal of the tape. This was proven by retropubic implantation of Mersilene tapes in female dogs, in the position of the pubo-urethral ligament. The procedure relies on the normally negative aspects of wound healing for its effect, such as foreign body reaction, bacterial colonization, and continued tissue breakdown and regeneration.

In this Theory paper, the complex interplay of the specific structures involved in female urinary continence are analyzed. In addition the effects of age, hormones, and iatrogenically induced scar tissue on these structures, are discussed specifically with regard to understanding the proper basis for treatment of urinary incontinence. According to the Theory stress and urge symptoms may both derive, for different reasons from the same anatomical defect, a lax vagina. This laxity may be caused by defects within the vaginal wall itself, or its supporting structures i.e. ligaments, muscles, and their connective tissue insertions. The vagina has a dual function. It mediates (transmits) the various muscle movements involved in bladder neck opening and closure through three separate closure mechanisms. It also has a structural function, and prevents urgency by supporting the hypothesized stretch receptors at the proximal urethra and bladder neck. Altered collagen/elastin in the vaginal connective tissue and/or its ligamentous supports may cause laxity. This dissipates the muscle contraction, causing stress incontinence, and/or activation of an inappropriate micturition reflex, ("bladder instability") by stimulation of bladder base stretch receptors. The latter is manifested by symptoms of frequency, urgency, nocturia with or without urine loss.

Seventeen women, 14 with urge incontinence, and 3 with debilitating sensory urgency symptoms were operated on with a combined Intravaginal Sling operation and Tuck procedure. All but three were cured of their preoperative symptoms. The reason for the high cure rate achieved may be explained by restoration of anatomical support below the bladder neck. This prevents the stretch receptors from firing off at rest. Importantly, Intravaginal Sling operation and Tuck procedure do not elevate the bladder neck, so that these stretch/pain receptors are not stimulated by the elevation process. The results accord with the Integral Theory of Female Urinary Incontinence, which states that urge as well as stress symptoms may derive from the same anatomical defect, a loose vagina.

A minor operative procedure involving the excision of bilateral small elliptical 1 x 0.5 cm pieces of vaginal mucosa is described as a proposed alternative to a Kelly Repair. Twelve month success rate was 47%. The modus operandi of the procedure is examined with reference to the Integral Theory of Female Urinary Incontinence, as are the possible reasons for the operative failure.

Ten patients are presented with symptoms of urinary stress and/or urgency. Eight were cured by approximation of the uterosacral ligaments. This supports the contention of the Integral Theory of Female Urinary Incontinence that a loosely tethered supralevator vagina may be an important element in urinary incontinence, especially following hysterectomy.

Six patients, average age 80 years, with no previous operations, presented with urinary incontinence. The predominant symptoms were "being wet all the time" and "sudden uncontrolled urine loss". They had no symptoms of urgency or stress incontinence, and no objective evidence of "detrusor instability" or urine loss on cough stress pad testing. All but one patients were cured by the simultaneous combined Intravaginal Sling and Tuck operation, indicating that the primary cause of the symptoms was an anatomical defect in the vagina and the ligamentous supports in the region of the bladder neck, as stated in the Integral Theory of Urinary Incontinence, this supplement, elderly.

This office test reinforces the Integral Theory of Female Urinary continence which states that there are two distinct anatomical segments of vagina which transmit the muscular contractions of the pelvic floor muscles, and in so doing, constitute the 1st and 2nd closure mechanisms. The test is based on tightening the loose vagina, hereby correcting the anatomical defects causing the stress incontinence. The Pinch Test, and with it, the Bonney Test, are analysed with reference to the 1st and 2nd closure mechanisms presented in the Theory of Female Urinary Incontinence described earlier in this issue.

The in vitro release profile of prostaglandin E2 (PGE2) from a starch polymer hydrogel was studied. Using a diffusion cell apparatus the in vitro release was measured in a cumulative manner based on a steady-state diffusion concept. The results showed that PGE2 was slowly released for a total of 18 hours. The rate of release was constant for up to 2 hours before changing to a lower value for the remaining time period. The PGE2-hydrogel showed sustained release characteristics which could be of significance in the clinical situation in providing a delayed release mechanism.

Uterine hypercontractility is considered to be an important factor in primary dysmenorrhea. A survey is given on possible mechanisms controlling the cytoplasmic concentration of free calcium and thereby contractile activity in the myometrial smooth muscle cell. Probably acting by different modes of action, inhibitors of prostaglandin synthesis, calcium antagonists and beta 2 stimulators have all been shown to reduce myometrial activity and relieve dysmenorrheic pain. The possibility of achieving further uterine relaxation after initial treatment with prostaglandin inhibitors by adding a calcium antagonist such as nifedipine is discussed. It is also suggested that when utilizing a reliable pressure recording technique in the evaluation of dysmenorrheic patients, the pronounced myometrial relaxation obtained by such combined therapy may be of diagnostic value.

In 54 patients with an unripe cervix in late third trimester, in which gestational age had been properly determined by repeated ultrasound scannings, labor was induced by intracervical application of 0.5 mg PGE2 in viscous gel. It was found that the outcome of the induced labor was not related to the gestational duration, but to the pre-inductive cervical score. Thus, the number of successful inductions was smaller and induction-delivery time longer, the lower the cervical score. Moreover, instrumental deliveries occurred most frequently in nulliparous women, with a low pre-inductive cervical score. Taking into consideration the difficulties of labor induction in the present type of patient, the overall proportion of instrumental deliveries (17%, including 7% cesarean sections) was low. No maternal or fetal side effects were observed. It is concluded that intracervical application a small dose of PGE2 in gel can be recommended for cervical priming and labor induction in pre- and post-term pregnancy.

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.

In 100 pregnant women at term, labor was induced for medical reasons by i.v. infusion of a low dose of prostaglandin F2 alpha (PGF2 alpha). With a dose not exceeding 6 micrograms PGF2 alpha/min, all patients were induced into labor. The mean induction-delivery time was 6.6 hours and the overall proportion of instrumental deliveries was 19%, including 6% cesarean sections. Very few side effects were observed. It is concluded that i.v. infusion of prostaglandin F2 alpha in a low dose regimen might be considered as an alternative to existing methods for the induction of labor at term.

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.

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.

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.

In this survey the effect of intracervically applied prostaglandin E2 (PGE2) on the pregnant uterus is outlined. It is concluded that PGE2 decreases cervical resistance and stimulates the myometrium to contract. In small doses (0.25 mg and 0.5 mg) PGE2 produces a rapid and prominent ripening of the cervix without systemic side effects and indepedent of prominent uterine contractions. Prostaglandin E2 applied intracervically in viscous gel seems to be superior to previously used methods for treatment of patients with an unfavorable cervical state.

The methods used to date to ripen the unfavorable cervix during pregnancy have considerable disadvantages, chiefly from the practical point of view. Intracervical application of a small dose (0.5 mg) of prostaglandin E2 (PGE2) in viscous gel is a safe, easily performed and effective method to ripen the cervix in both early and late pregnancy. A new starch-based gel seems to have solved the pharmaceutical problems associated with gel preparations used hitherto. The histological and biochemical changes induced by local application of PGE2 are similar to those occurring spontaneously during late pregnancy.