Lower urinary tract injury during the Burch procedure: is there a role for routine cystoscopy?

OBJECTIVE: This study was undertaken to evaluate the use of intraoperative cystoscopy for the detection of incidental bladder or ureteral injuries during abdominal urethropexy procedures and to determine whether the incidence of injuries warrants the routine use of cystoscopy. METHODS: We reviewed the medical records of 109 consecutive patients who underwent abdominal urethropexy procedures between November 1990 and February 1996 at a teaching institution. Each underwent intraoperative cystoscopy. We determined the incidence of cystotomy and ureteral obstruction and attempted to determine surgical factors that might be associated with an increased risk of injury. RESULTS: Ten of 109 patients (9%) had bladder or ureteral injury, including 1 cystotomy during retropubic dissection, 6 cases of a transvesical suture noted during cystoscopy, 1 cystotomy recognized before closure, 1 case of ureteral obstruction found during cystoscopy, and 1 case of ureteral obstruction not recognized at cystoscopy. Cystoscopy allowed detection of 7 of 9 (78%) otherwise unrecognized events. The only injury that resulted in significant postoperative morbidity was the unrecognized ureteral obstruction. There was no association between incidence of lower urinary tract injuries and surgical risk factors. CONCLUSION: Intraoperative bladder or ureteral injuries during urethropexy procedures are not uncommon, with an incidence of 9% in our series. There is minimal morbidity if these injuries are detected and corrected during the operation, whereas morbidity may be significant if they remain unrecognized. With a potential for unrecognized injury in 8% of Burch procedures without the use of cystoscopy, routine use of cystoscopy during urethropexy procedures appears to be warranted.

Role of the insulin-like growth factor system in uterine function and placental development in ruminants.

Maternal nutrition during pregnancy influences fetal and placental weights. The insulin-like growth factors (IGF) are also important determinants of fetal size. Furthermore, the expression of several components of the IGF system is regulated by nutrition. Effects of nutrition on fetal growth could therefore be mediated by the IGF system in the uterus and placenta. The oviductal mucosa produces IGF-I, which may influence oviductal secretions or act directly on embryonic type 1 IGF receptors. In the uterus, IGF-I mRNA is localized to the stroma surrounding the endometrial glands, which contain high concentrations of IGF type 1 receptors. Uterine IGF-I concentrations fall during pregnancy; therefore, glandular activity is more likely influenced by systemic than local IGF-I production. The IGF-II mRNA is present in both caruncles and fetal placental mesoderm, but concentrations are much higher in the latter. The actions of IGF-I and IGF-II on the endometrium and placenta are influenced by IGF-binding proteins. In the ewe, mRNAs for IGF binding protein-1 and -5 are located in the luminal and glandular epithelia, IGF binding proteins-2 and -4 are produced in the subepithelial stroma, and IGF binding protein-4 is also in the placentome capsule; IGF binding protein-3 is more widely expressed in both maternal and fetal tissues. The IGF binding proteins, therefore, form a major barrier to the passage of IGF between the fetal and maternal circulatory systems.

Pregnancy-specific alterations in the expression of the insulin-like growth factor system during early placental development in the ewe.

The placenta is recognized as an important determinant of fetal growth rate, yet the factors regulating its proliferation remain poorly understood. Components of the insulin-like growth factor (IGF) system were localized in the ovine uterus using in situ hybridization between days 13-55 of gestation, the period of implantation and placentome formation. IGF-II messenger RNA (mRNA) expression was intense in the fetal mesoderm, particularly at the tips of the invading placentome villi. Moderate levels of IGF-II mRNA were also observed in the maternal caruncular stroma. In contrast, expression of IGF-1 mRNA was low (compared to estrous levels) and ubiquitous decreasing as gestation advanced. IGF-binding protein-2 (IGFBP-2 mRNA was not detected until day 29 of gestation, when it appeared restricted to the dense caruncular-like stroma lining the luminal epithelium, colocalized with IGFBP-4. High concentrations of IGFBP-4 mRNA expression were also found in the placentome capsule. IGFBP-3 mRNA expression was intense in the luminal epithelium between days 13-15 of gestation. Subsequently, levels in this region dropped significantly (P < 0.001). IGFBP-3 mRNA expression was also high in the maternal placentome villi, where photographic emulsions localized expression to blood vessel walls. Peak expression of IGF type 1 receptor (IGF-1R) mRNA was found in the deep uterine glands, with intermediate expression in the superficial uterine glands. Moderate expression of IGF-1R mRNA was initially recorded in caruncular stroma, but levels in this region decreased significantly (P < 0.001) to below the detection limit of the technique after interdigitation by the fetal allantochorion. Furthermore, IGF-1R mRNA could not be detected in any fetal placentome tissue. This study, therefore, has established the pattern of expression of the IGFs, IGF-1R, and three of the IGFBPs during establishment of the ovine placenta. It will form the basis for future work to investigate how this system is regulated and to determine the role of the IGFs in placental development.

Regulation of oxytocin, oestradiol and progesterone receptor concentrations in different uterine regions by oestradiol, progesterone and oxytocin in ovariectomized ewes.

The regulation of oxytocin, oestradiol and progesterone receptors in different uterine cell types was studied in ovariectomized ewes. Animals were pretreated with a progestogen sponge for 10 days followed by 2 days of high-dose oestradiol to simulate oestrus. They then received either low-dose oestradiol (Group E), low-dose oestradiol plus progesterone (Group P) or low-dose oestradiol, progesterone and oxytocin (via osmotic minipump; Group OT). Animals (three to six per time-point) were killed following ovariectomy (Group OVX), at oestrus (Group O) or following 8, 10, 12 or 14 days of E, P or OT treatment. In a final group, oxytocin was withdrawn on day 12 and ewes were killed on day 14 (Group OTW). Oxytocin receptor concentrations and localization in the endometrium and myometrium were measured by radioreceptor assay, in situ hybridization and autoradiography with the iodinated oxytocin receptor antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]-vasotocin. Oestradiol and progesterone receptors were localized by immunocytochemistry. Oxytocin receptors were present in the luminal epithelium and superficial glands of ovariectomized ewes. In Group O, endometrial oxytocin receptor concentrations were high (1346 +/- 379 fmol [3H]oxytocin bound mg protein-1) and receptors were also located in the deep glands and caruncular stroma in a pattern resembling that found at natural oestrus. Continuing low-dose oestradiol was unable to sustain high endometrial oxytocin receptor concentrations with values decreasing significantly to 140 +/- 20 fmol mg protein-1 (P < 0.01), localized to the luminal epithelium and caruncular stroma but not the glands. Progesterone treatment initially abolished all oxytocin receptors with none present on days 8 or 10. They reappeared in the luminal epithelium only between days 12 and 14 to give an overall concentration of 306 +/- 50 fmol mg protein-1. Oxytocin treatment caused a small increase in oxytocin receptor concentration in the luminal epithelium on days 8 and 10 (20 +/- 4 in Group P and 107 +/- 35 fmol mg protein-1 in Group OT, P < 0.01) but the rise on day 14 was not affected (267 +/- 82 in Group OT and 411 +/- 120 fmol mg protein-1 in Group OTW). In contrast, oestradiol treatment was able to sustain myometrial oxytocin receptors (635 +/- 277 fmol mg protein-1 in Group O and 255 +/- 36 in Group E) and there was no increase over time in Groups P, OT and OTW with values of 61 +/- 18, 88 +/- 53 and 114 +/- 76 fmol mg protein-1 respectively (combined values for days 8-14). Oestradiol receptor concentrations were high in all uterine regions in Group O. This pattern and concentration was maintained in Group E. In all progesterone-treated ewes, oestradiol receptor concentrations were lower in all regions at all time-points. The only time-related change occurred in the luminal epithelium in which oestradiol receptors were undetectable on day 8 but developed by day 10 of progesterone treatment. Progesterone receptors were present at moderate concentrations in the deep glands, caruncular stroma, deep stroma and myometrium in Group O. Oestradiol increased progesterone receptors in the luminal epithelium, superficial glands, deep stroma and myometrium. Progesterone caused the loss of its own receptor from the luminal epithelium and superficial glands and decreased its receptor concentration in the deep stroma and myometrium at all time-points. There was a time-related loss of progesterone receptors from the deep glands of progesterone-treated ewes between days 8 and 14. These results show differences in the regulation of receptors between uterine regions. In particular loss of the negative inhibition by progesterone on the oxytocin receptor by day 14 occurred only in the luminal epithelium, but is unlikely to be a direct effect of progesterone as no progesterone receptors were present on luminal epithelial cells between days 8 and 14.

Voiding dysfunction in women.

Voiding disorders are frequently associated with urinary incontinence and other lower urinary tract dysfunction in women, but the cause of these disorders is not well understood and treatment options are limited. Little has changed in the treatment and evaluation of voiding disorders. New approaches to the study of detrusor function have added insights into the etiology of these disorders.

Insulin-like growth factors and their binding proteins in the ovine oviduct during the oestrous cycle.

The oviduct is the site of fertilization, and factors present in the oviductal fluid appear to be crucial to the future success of conceptus development. The spatial and temporal localization of mRNA encoding components of the insulin-like growth factor (IGF) system (IGF-I, IGF-II, the type 1 IGF receptor, and IGF-binding proteins -2, -3 and -4) in the ovine oviduct were examined in tissue samples taken during the early and late stages of follicular development, and the early, mid-, and late luteal phases using in situ hybridization. Expression of mRNA encoding IGF-I showed a cyclical pattern, increasing sharply in the mucosa and muscularis during the late follicular phase (P < or = 0.001), then declining. In the muscularis, mRNA encoding IGF-II exhibited no temporal changes, but concentrations in the mucosa increased from the late follicular stage to the early luteal phase. mRNA encoding the type 1 IGF receptor was present throughout the oviduct. Concentrations increased during the follicular phase to peak in the early luteal phase in both the mucosa and muscularis (P < 0.001). IGFBP-2 gene transcripts were undetectable at all time points examined. mRNAs encoding IGFBP-3 and IGFBP-4 were localized primarily in the stromal region. IGFBP-3 expression peaked in the late follicular stage of the cycle P < or = 0.001). The concentration of mRNA encoding IGFBP-4 increased in the follicular phase and was maintained at a significantly higher concentration during the early and mid-luteal stages (P < 0.001). The co-ordinate maximum expression of mRNA for both IGF-I and IGF-II, the type 1 IGF receptor and IGFBP-3 during the period when the gametes and embryo are in transit suggests a role for IGF-I and possibly IGF-II peptides in providing an oviductal environment propitious to conception and early embryonic growth and metabolism.

Oxytocin receptor development in ovine uterus and cervix throughout pregnancy and at parturition as determined by in situ hybridization analysis.

The development of uterine oxytocin receptors is an important regulatory step in the initiation of labour. Paracrine production of oxytocin by uterine and placental tissues may also be involved in some species. Placentome, intercotyledonary endometrium, myometrium and fetal membranes were collected from 3-5 ewes each, at regular intervals throughout pregnancy and from eight ewes during labour. Localization of mRNA encoding oxytocin and its receptor was by in situ hybridization; oxytocin peptide concentrations were measured by radioimmunoassay and oxytocin receptor concentrations were measured by autoradiography and radioreceptor assay. In the intercotyledonary endometrium, mRNA encoding the oxytocin receptor was located in the luminal epithelium only. Both the epithelial and myometrial receptors were detected at low concentrations from the fourth week of gestation onwards, with a major increase associated with the onset of labour. In the placentomes, oxytocin receptors were localized to a stromal capsule surrounding the placental villi. Expression in this region was maximal in mid-gestation, declining in the second half of pregnancy and remaining low during labour. Cervical oxytocin receptors were detected at low concentrations in the epithelium and the muscular/connective tissue layers from day 22 of pregnancy onwards. There was no evidence for the local uterine production of oxytocin in the ewe; mRNA encoding oxytocin was undetectable and oxytocin concentrations were always < 23 pg g-1 wet mass of tissue. These results suggest that regulation of the timing of oxytocin receptor development varies between the different tissue types, despite a similar steroidal background. The receptors in the luminal epithelium are probably associated with the ability of exogenous oxytocin to induce the release of PGF2 alpha throughout most of pregnancy. The increase in receptors in both the intercotyledonary endometrium and myometrium at term suggest an involvement in labour, whereas their role in caruncular stroma in mid-pregnancy is unknown.

Sling transection of urethra: a rare complication.

Common postoperative complications associated with suburethral sling procedures include voiding disorders and urinary retention, de novo development of detrusor instability, sling graft rejection and, rarely, erosion of the graft into the urethra. The authors present a case of a late postoperative complication of polytetrafluoroethylene graft erosion and partial transection of the urethra, with resultant acute urinary retention. A 50-year-old patient presented with acute urethral outflow obstruction due to sling graft erosion into the urethra nearly 2 years after she underwent a curative sling procedure for recurrent genuine stress incontinence. After relieving the acute urinary retention by inserting a suprapubic catheter under ultrasound guidance, the sling graft was accessed and removed. The urethral defect was repaired successfully. At follow-up 5 months later, the patient was continent subjectively and by urodynamic criteria, with no voiding abnormalities. Although erosion of the sling graft into the urethra and transection of this structure is a rare complication after a sling procedure, it should be considered in the patient who experiences progressive voiding difficulties, has transvaginal urinary leakage, and/or cannot be catheterized transurethrally. Expedient relief of the urinary retention and outflow obstruction is necessary, as well as careful surgical reconstruction of the urethra. To minimize the development of this complication we recommend plication of paraurethral connective tissue in the midline beneath the sling graft, and placement of minimal tension on the sling.

Local action of trophoblast interferons in suppression of the development of oxytocin and oestradiol receptors in ovine endometrium.

Luteolysis in sheep is associated with uterine secretion of pulses of prostaglandin F2 alpha (PGF2 alpha) due to the action of luteal oxytocin on endometrial oxytocin receptors. For pregnancy to become established inhibition of oxytocin receptors is important as an antiluteolytic mechanism. The maternal recognition of pregnancy in cattle and sheep involves production, by the trophoblast, of a type 1 interferon (IFN-tau) that suppresses uterine development of oxytocin receptors and the generation of luteolytic episodes of PGF2 alpha. The action of IFN-tau in surgically prepared unilaterally pregnant ewes was investigated. Finn-Dorset ewes were anaesthetized on day 6 or 7 of the oestrous cycle and one uterine horn was surgically isolated at the uterine bifurcation from the body of the uterus. Ewes were mated at the subsequent oestrus either by a fertile or by a vasectomized ram and killed on day 13 or 16 after mating. On day 16, in the non-pregnant ewes, there was no measurable uterine IFN-tau but there were high concentrations of oxytocin receptors in both horns. In the pregnant ewes on day 16 after mating, the oxytocin receptor concentration was 45 +/- 11 fmol mg-1 protein in the pregnant horn and 585 +/- 131 fmol mg-1 in the non-pregnant horn. Antiviral activity was 5.8 x 10(7) +/- 5.2 x 10(7) U ml-1 in the pregnant horn and 2.9 x 10(3) +/- 1.2 x 10(3) U ml-1 in the non-pregnant horn. Thus, 16 days after mating, the pregnant horn exhibited high antiviral activity but oxytocin receptors were suppressed, while in the same endocrine environment (characteristic of pregnancy) there were low IFN-tau and high oxytocin receptor concentrations in the isolated horn equivalent to those expected at the onset of luteolysis. In situ hybridization to ovine mRNA encoding the oxytocin receptor and autoradiographic studies using the 125I-labelled oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]-vasotocin both showed that the large amount of oxytocin receptor message and binding sites in the endometrium of the isolated horn were localized in the luminal epithelium. Immunocytochemical studies showed that there was a suppression of oestradiol receptors in the pregnant horn but high concentrations equivalent to those at oestrus were present in the isolated horn. The content of progesterone receptors was low in the stromal tissue only in both horns, a pattern of localization similar to that seen in the late luteal phase and in early pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)

Localization of insulin-like growth factor-I (IGF-I) and -II messenger ribonucleic acid and type 1 IGF receptors in the ovine uterus during the estrous cycle and early pregnancy.

Insulin-like growth factor-I (IGF-I), IGF-II, and the type 1 IGF receptor (IGF-IR) gene transcripts were localized in sections of ovine uterus collected from 53 ewes at different stages during the estrous cycle and the first 3 weeks of pregnancy using in situ hybridization with synthetic oligonucleotides. Binding studies on cryostat sections using [125I]IGF-I or [125I]des(1-3)IGF-I were carried out to assess whether binding sites for IGF-I colocalized with sites of IGF-IR gene transcription. Peak IGF-I mRNA concentrations occurred at estrus in both the periepithelial endometrial stromal cells and the longitudinal and circular muscle cells of the myometrium. Concentrations of transcript returned to basal levels by 48 h after estrus. The variations in IGF-I mRNA concentration during the estrous cycle showed significant correlations with the estradiol receptor concentration in the same cell types, measured in the same animals by immunocytochemistry (P < 0.01). IGF-II mRNA was localized exclusively to the caruncular stroma (high transcription) and endometrial stroma (low transcription), with levels showing no positive correlation to the concentration of estradiol receptors, progesterone receptors, or plasma progesterone, but decreasing gradually between estrus and days 14-15 (P < 0.05). IGF-IR mRNA was localized mainly to the deep and superficial glandular epithelium, with lower levels of transcription in the caruncular stroma and myometrium. Transcription in the deep glands remained high throughout the cycle, but in the superficial glands and myometrium, a small peak occurred in the early luteal phase (days 1-2), 24-48 h after peak IGF-I gene transcription. [125I]IGF-I- and des(1-3)IGF-I-binding sites colocalized with sites of IGF-IR gene transcription. Additional binding sites were revealed with the iodinated ligands in the myometrium, superficial glands, deep stroma, and blood vessel walls, which were probably attributable to the presence of binding proteins (IGFBPs). The different affinities of des(1-3)IGF-I for IGFBP-3, -2, and -1 lead us to suggest that IGFBP-2 and/or -1 are present in the deep stroma and glands, whereas IGFBP-3 may be responsible for the additional binding sites in the myometrium and blood vessel walls. Comparisons between pregnant and nonpregnant ewes on days 2-15 after estrus did not reveal any clear pregnancy-associated differences in either the sites or levels of IGF-I, IGF-II, or IGF-IR gene transcription.

Localization of oxytocin receptor mRNA in the ovine uterus during the oestrous cycle and early pregnancy.

A synthetic 45-mer oligonucleotide corresponding to part of the ovine endometrial oxytocin receptor cDNA was hybridized to sections of ovine uterus collected from 40 ewes at different stages during the oestrous cycle, the first 3 weeks of pregnancy and seasonal anoestrus. The quantity of oxytocin receptor mRNA was measured as the optical density (OD) value on autoradiographs using image analysis. Message first appeared in the luminal epithelium on days 14-15 of the cycle, increasing to a peak OD of 0.48 at oestrus and decreasing again between days 2 and 5. Oxytocin receptor mRNA in the superficial glands, deep glands and caruncular stroma increased between day 15 and oestrous to peak OD values of 0.17, 0.11 and 0.11 respectively, declining again by day 2 and reaching basal values (OD < 0.015) by day 5. Hybridization to the myometrium tended to rise from a mean OD value of 0.01 on days 2-15 to a peak of 0.03 +/- 0.01 (mean +/- S.E.M.) on days 0-1, but the change was not significant. In pregnant ewes there was no detectable oxytocin receptor mRNA on days 14-15 in any region, but hybridization to the luminal epithelium was present in two of three ewes on day 21. In anoestrous ewes oxytocin receptor mRNA concentrations in all areas of the endometrium were approximately half those measured at oestrus. Optical density readings for oxytocin receptor mRNA in the various uterine compartments were compared with measurements of oxytocin receptors in the same regions as assessed by binding studies using the 125I-labelled oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]-vasotocin (125I-labelled OTA). In the endometrium, receptor mRNA and 125I-labelled OTA binding patterns changed in parallel, and both sets of measurements were significantly correlated (P < 0.01). In the myometrium, a significant increase in 125I-labelled OTA binding occurred at oestrus; this was not accompanied by a similar increase in oxytocin receptor mRNA hybridization. This study helps to confirm that the previously identified cDNA clone is derived from the ovine oxytocin receptor, as patterns of oxytocin receptor mRNA expression in the endometrium closely resembled those of oxytocin binding. Maximum expression and binding both occurred at oestrus, suggesting that regulation of the oxytocin receptor gene in the uterus occurs principally at the transcriptional, rather than at the translational, level. Failure to detect a significant increase in myometrial mRNA expression at oestrus may indicate that the endometrial and myometrial oxytocin receptors are of different isoforms.

Isolation and structure of a partial sheep oxytocin receptor cDNA and its use as a probe for northern analysis of endometrial RNA.

The polymerase chain reaction (PCR) was used to generate a 131 bp cDNA encoding part of the sheep endometrial oxytocin receptor. The nucleotide sequence of this cDNA was 93.8% identical to the human oxytocin receptor sequence in this region. When used to probe Northern blots of sheep endometrial RNA the PCR product identified a 6.7 kb mRNA which appeared and disappeared during the oestrous cycle in parallel with the oxytocin receptor molecule as measured by ligand binding. The sheep endometrial receptor mRNA was significantly larger than the human myometrial mRNA (4.7 kb). It is suggested that the cloned cDNA described here is an appropriate probe for use where it is required to measure sheep oxytocin receptor mRNA.

Measurement of oxytocin concentrations in plasma and ovarian extracts during the oestrous cycle of mares.

Jugular venous blood samples were collected throughout a complete oestrous cycle from 9 mares for measurement of progesterone and oxytocin by radioimmunoassay. Mean oxytocin concentrations remained at approximately 1 pg/ml throughout, with no evidence of cyclic variation in the release pattern. Extracts of corpus luteum and follicles obtained from a further 33 mares at different stages of the cycle all contained oxytocin concentrations of less than 10 pg/g wet weight of tissue. We conclude that the ovaries are not a source of circulating oxytocin during the oestrous cycle in this species. The plasma oxytocin concentrations reported here are substantially lower than those found by other groups.

Small center kidney transplantation.

We herein present the results of our first 100 kidney transplants. The 1-year patient and graft survivals were 94 and 74 per cent, respectively, for living related grafts, and 85 and 57 per cent, respectively, for cadaver grafts. These results compare favorably to the recent standards set by the American Society of Transplant Surgeons Standards Committee (95.1, 78.6, 88.6 and 55 per cent). Initial hospitalization averaged 21 plus or minus 7 days, while hospitalization during the first year after transplantation averaged 35 plus or minus 21 days. Average expenses (Medicare reimbursed) during the first 12 months after kidney placement were $29,572 plus or minus $6,468 for 15 successive patients. A total of 22 complications occurred within 1 year of transplantation and 11 required surgical management. Of 24 patients who survived 1 year with loss of graft function 15 (62 per cent) required transplant nephrectomy. Causes of death and types of complications are presented. Our results suggest that high quality kidney transplantation may be available to patients in small transplant centers.