Urinary leakage during coitus in women.

During a 4-year period from 1993 to 1997, a total of 2153 women were referred to our urogynaecology clinic complaining of urinary incontinence. Of these women, 228 (10.6%) admitted to coital incontinence. Only 22 of these 228 women complained of this symptom without direct questioning. Urine loss occurred during penetration in 158 women, during orgasm in 45 women and during both in 25 women. Comparison of these groups showed few other differences in their presenting symptoms, examination findings, urodynamic data or diagnosis. Genuine stress incontinence was present in 79.8% of women with urinary leakage during penetration, in 93.2% with leak on orgasm and in 92.0% who leaked on both. Detrusor instability was uncommon. In most women who complain of urinary leakage during sexual intercourse, the underlying pathophysiological mechanism is urethral sphincter incompetence. Compared with women presenting with urinary incontinence in the absence of coital incontinence, women with coital leakage had a higher incidence of stress and urge incontinence, and a significantly greater incidence of anterior vaginal wall prolapse and demonstrable stress incontinence on examination.

Burch colposuspension for the treatment of coital urinary leakage secondary to genuine stress incontinence.

The efficacy of Burch colposuspension in treating the symptom of coital urinary leakage in women with genuine stress incontinence has to date never been reported. Women who presented to our clinic with regular coital urinary leakage and urodynamically proven genuine stress incontinence between 1993 and 1997, and who proceeded to a Burch colposuspension procedure, were reviewed to determine the outcome of surgery. Fifty-five women were identified (mean age 46.1 years) with a mean follow-up interval after surgery of 18 months (range 3-42 months). All 55 women had symptoms of stress, urge and coital incontinence preoperatively. Following colposuspension, the subjective cure rates for stress and urge incontinence were 84% and 85%, respectively. Of 52 women that were sexually active after surgery, 81% described no further coital incontinence. The success or failure of surgery was not influenced by whether leakage occurred with penetration or orgasm preoperatively.

Inhibitory potency of isoprenaline on guinea-pig and gravid human myometrium following extraneuronal uptake blockade.

The hypothesis that inhibitory effects of isoprenaline on myometrial contractility may be constrained by activation of putative intracellular beta-adrenoceptors negatively-coupled to adenylate cyclase was examined. Field-stimulated preparations of guinea-pig and human myometrium were used to examine the influence of the catecholamine extraneuronal uptake2 inhibitors, corticosterone and beta-oestradiol, on the inhibitory effects of the beta-adrenoceptor agonist, isoprenaline, on uterine contraction. Longitudinal and circular myometrial layers were obtained from guinea-pigs in dioestrus, primed with oestrogen before progesterone, or pregnant (Days 62-65). In the guinea-pig myometrium, corticosterone (30 microM) did not affect responses to isoprenaline. beta-oestradiol (10 microM) induced a small potentiation of the effects of isoprenaline on longitudinal myometrium from dioestrus guinea-pigs. Myometrial preparations were obtained from pregnant women (36-40 weeks gestation) undergoing caesarean section. Isoprenaline inhibited stimulation-evoked contractions in 7 of 10 preparations of the inner myometrial layer and in 5 of 8 preparations of outer myometrial layer. Corticosterone (30 microM) reduced the effects of isoprenaline on the inner layer and did not affect the outer layer. These results do not support the existence of mechanism involving isoprenaline-sensitive intracellular receptors which constrain responses to beta-adrenoceptor agonists.

Supersensitivity to the stimulant action of noradrenaline on human myometrium near term.

Noradrenaline (10-50 nM) and tyramine (0.05-1 mM) enhanced contractile force elicited by field stimulation of strips of myometrium from non-pregnant and pregnant women. In higher concentrations, noradrenaline produced sustained contractions. The EC50 values for noradrenaline were 0.4 microM in tissues from pregnant women and 3.1 microM in tissues from non-pregnant women; maximum responses were greater in the former tissues. In addition, the effects of noradrenaline on myometrium from pregnant women were more marked on the inner layer than on the outer layer, antagonized by the alpha 1-adrenoceptor antagonist prazosin (0.1 and 1.0 microM), and unaffected by the inhibitor of neuronal uptake, nisoxetine (0.1 microM). Taken together, these observations confirm that supersensitivity to noradrenaline develops during pregnancy and is present near term. The supersensitivity to noradrenaline at term can be attributed only in part to a decrease in its removal by the sympathetic innervation, which declines towards term, because responses to tyramine were also enhanced in tissues from pregnant women. It is possible that gap junction formation may also contribute to this supersensitivity.

The actions of tulobuterol on isolated preparations of gravid human myometrium.

1. The effects of tulobuterol (Abbott 54173) on the contractile force developed by electrically stimulated strips of gravid (gestation 36-40 weeks) human uterine muscle were compared with those of isoprenaline and adrenalin. 2. Isoprenaline produced inhibition of electrically evoked contractions of myometrium from 12 of 17 women at concentrations at or below 1 mumol/L (range 0.001-1 mumol/L). It enhanced contractions at concentrations of 10-50 mumol/L. In tissues from the remaining five women isoprenaline produced neither inhibitory nor excitatory effects. Adrenalin (0.1-50 mumol/L) was found to enhance contractile force in a concentration-dependent manner (EC50 = 0.30 mumol/L). 3. In the presence of metoprolol (0.3 mumol/L), a selective antagonist at beta 1-adrenoceptors, the isoprenaline concentration-response relationship was shifted to the left, indicating that beta 1-adrenoceptors are present and that they mediate excitation in the human uterus. 4. In contrast tulobuterol (in neither the presence nor absence of metoprolol), in the same concentration range as isoprenaline and adrenalin, (0.001-50 mumol/L) was found to have no effect on the electrically evoked contraction of gravid human uterine muscle strips.

Effects of adrenaline, isoprenaline and forskolin on pregnant human myometrial preparations.

1. The effects of adrenaline, isoprenaline and forskolin upon the evoked contractions of field-stimulated preparations of human, pregnant, isolated myometrium have been examined. Specimens were obtained at lower segment Caesarean section from patients at 31 (n = 1) and 36-40 (n = 10) weeks of gestation. 2. Adrenaline enhanced the electrically evoked contractions of all preparations studied, indicating that its predominant action on these pregnant myometrial tissues was at alpha- and not beta-adrenoceptors. 3. Isoprenaline in concentrations at and below 10 mumol/l produced inhibitory effects in eight of 11 experiments. In the remaining three experiments, tissues were not responsive to the inhibitory effects of isoprenaline. 4. In all preparations exposed to higher concentrations of isoprenaline (30 or 100 mumol/l), its effects were excitatory. 5. Forskolin produced inhibitory effects on preparations from all uteri, including those from which tissues unresponsive to isoprenaline had been obtained. 6. It is suggested that forskolin in the concentrations which were effective in this study produced its inhibitory effects largely through activation of adenylate cyclase. This implies that the lack of an inhibitory response of some preparations to isoprenaline was not due to reduced activity of the adenylate cyclase system, but that the failure of isoprenaline to produce an inhibitory effect could be due to diminished numbers of beta-adrenoceptors and/or increased numbers of alpha-adrenoceptors, or to a defect in the coupling of the receptors to the adenylate cyclase system. Alternatively, the presence of an endogenous antagonist of the effects of isoprenaline (for example, an eicosanoid), could mask its inhibitory effects. 7. The absence of an inhibitory effect of isoprenaline on some specimens of human gravid myometrium could have clinical implications, in view of the widespread use of beta 2-adrenoceptor agonists as uterine relaxants.

Pharmacokinetics of intravenous and oral salbutamol and its sulphate conjugate.

The pharmacokinetics of salbutamol and its sulphate conjugate metabolite were investigated after intravenous and steady-state oral administration of salbutamol to 10 healthy volunteers. With intravenous administration, total plasma clearance was 480 +/- 123 ml min-1, elimination half-life was 3.86 +/- 0.83 h and apparent volume of distribution was 156 +/- 381. Urinary excretion of unchanged drug and sulphate conjugate were 64.2 +/- 7.1% and 12.0 +/- 3.1% of the dose, respectively. With oral administration, systemic availability was 0.50 +/- 0.04, and urinary excretion of unchanged drug and sulphate conjugate were 31.8 +/- 1.9% and 48.2 +/- 7.3% of the dose, respectively. The drug eliminated on the first-pass could be accounted for entirely as sulphate conjugate formed, presumably, in the intestinal wall. Renal clearance of salbutamol was 291 +/- 70 ml min-1 after intravenous and 272 +/- 38 ml min-1 after oral administration, while the renal clearance of the sulphate conjugate was 98.5 +/- 23.5 ml min-1 after oral administration. Heart rate increased with increasing plasma salbutamol concentration, although a lag was evident. The effect on heart rate was lower after 24 h continuous oral salbutamol administration.

Reflexes in cat ankle muscles after landing from falls.

1. Electrical activity and length of ankle muscles were recorded by telemetry during free fall and landing in cats. 2. After foot contact, there was a delay in onset of stretch of ankle extensors of between 8 and 11 ms. High-speed cinematography showed the delay to be associated with rapid initial dorsiflexion of the toes. 3. Electromyograms (e.m.g.) from lateral gastrocnemius increased in amplitude prior to landing. An early depression of lateral gastrocnemius e.m.g. commenced at 8 ms after foot contact, and was followed by a large peak of activity commencing some 8 ms after the first increase in lateral gastrocnemius length. 4. Local anaesthesia of the plantar cushion did not alter this pattern of response. 5. The early inhibition of lateral gastrocnemius was attributed to the action on lateral gastrocnemius motoneurones of non-cutaneous afferents responding to the initial toe dorsiflexion. Additional autogenetic inhibition may also have contributed. 6. The subsequent peak of e.m.g. was at a latenty consistent with a rapid stretch reflex, and occurred soon enough for the resulting active tension to contribute significantly to the extensor force during body deceleration.

Ia afferent activity during a variety of voluntary movements in the cat.

1. Implanted dorsal root electrodes were used to record discharge trains of single spindle primary afferents (Ia's) of the cat's hind limb during different types of movement.2. The length of the ipsilateral ankle extensors was continuously monitored by an implanted length gauge. Length changes occurring during active stepping were subsequently passively reproduced during brief anaesthesia.3. A comparison of the Ia responses in active and simulated step cycles revealed that moderate fusimotor drive to ankle extensor spindles probably occurred mainly, if not exclusively, during the E(1), E(2) and E(3) phases of active stepping.4. A temporal advance in the Ia response to passive stretching in the F-phase was attributed to the after-effects of fusimotor activity in the extension phases.5. Light thrust applied to the animal's back evoked a potent fusimotor response. This load compensation effect may provide an explanation for the apparently higher degree of alpha-gamma co-activation seen in the mesencephalic locomotor preparation.6. Ankle extensor Ia discharge decreased during falls, despite an increase in extensor e.m.g. This is seen as a clear example of independent alpha and gamma control.7. Placing reactions during walking were consistent with the notion that cutaneous inputs dominate over proprioceptive inputs in these movements.8. alpha and Ia discharge during paw-shaking showed many of the characteristics of that in decerebrate and spastic clonus. The present results suggest that movements resembling clonus may be part of the animal's normal repertoire.9. Isometric co-contraction of agonists and antagonists was found to involve alpha-gamma co-activation.10. Hamstring Ia discharge behaviour during stepping further highlighted the increases in firing rate which normally occur during passive muscle stretching in ;pre-programmed' movements.

Discharges of single hindlimb afferents in the freely moving cat.

1. Implanted semimicroelectrodes were used to record single afferent fiber discharges from L7 dorsal roots during unrestrained walking in the conscious cat. 2. A series of tests were used to identify an afferent during a short period of anesthesia following each recording session. The majority of afferents were from muscle spindle primary endings in hindlimb muscles. 3. Ankle extensor spindle primaries generally showed their highest firing rates during that phase of stepping in which they were passively stretched. During active muscle contraction there was evidence of fusimotor drive, although this was not usually sufficient to entirely overcome the unloading effect of rapid muscle shortening. The variability of firing rate from cycle to cycle was considerably greater for the phase of active muscle contraction. The EMG response to brisk stretches of the ankle extensor muscle indicated a rapid (disynaptic or trisynaptic) reflex arc in the conscious animal. 4. Knee flexor spindle primaries showed similarly higher firing rates during passive muscle stretching in the step cycle. The shorter periods of presumed alpha-gamma coactivation corresponded to the much more phasic role of these muscles in stepping. 5. Tendon organs in the physiological extensors of the toes were mainly active during stance, although some discharges were usually seen during the swing phase. It is suggested that previous experiments on mesencephalic preparations may have led to an exaggerated view of the degree of alpha-gamma coactivation during normal stepping movements.