Association of p53 mutations with metastatic prostate cancer.

In prostate cancer, mutation of the p53 tumor suppressor gene has been associated with locally advanced disease and hormone-resistant disease that is predominantly localized to bone. However, little is known regarding the status of the p53 gene in metastatic prostate cancer that has not been treated with hormonal manipulation. We evaluated formalin-fixed, paraffin-embedded malignant tissues from 86 patients with various stages of prostate cancer, including pathologically confined, locally advanced, and metastatic disease, to detect abnormal p53 nuclear protein accumulation using immunohistochemistry. No abnormal p53 immunostaining was detected in 18 patients with prostate cancer confined to the gland. Two tumors from 21 patients with locally advanced disease (extracapsular extension and/or seminal vesicle invasion) had abnormal nuclear p53 accumulation, and a mutation in exon 7 of the p53 gene was detected in tumor DNA from one patient using single-strand conformation polymorphism-direct sequencing analysis. Of the remaining 47 patients studied in whom tissues from the prostate gland and a metastatic site (44 lymph node, 2 bone, and 1 lung) were available, only 3 had received hormonal therapy prior to obtaining metastatic tissue. In four patients both primary and metastatic tumors demonstrated accumulation of p53 protein, whereas seven additional patients exhibited p53 accumulation only at the metastatic site. In three patients the metastatic tumors harbored missense single-base substitutions in exon 5, as detected using single-strand conformation polymorphism-direct sequencing. These results indicate that p53 abnormalities are associated with lymph node metastases derived from prostate cancer patients that had not undergone hormonal therapy.

Primary human prostate cancer cells harboring p53 mutations are clonally expanded in metastases.

Recent studies suggest a role for p53 in prostate cancer progression. Although p53 mutations in primary prostate cancer tissues are relatively infrequent, they occur at significant levels in metastatic disease. Here we describe a novel approach to the molecular analysis of p53 in paired specimens of primary and metastatic prostate cancer that results in quantitative estimates of the extent of clonal expansion. In 20 pairs with 1 or both specimens p53 immunopositive and in 6 pairs with both specimens immunonegative, the frequency of mutations was estimated by microdissection of the cancer from fixed and sectioned tissues, isolation of the DNA followed by PCR amplification of p53 genomic fragments, and cloning of the PCR products into plasmid vectors. At least 90 clones/tissue specimen were screened for mutations by single-strand conformational polymorphism analysis. DNA from abnormally migrating single-strand conformational polymorphism samples was sequenced to confirm mutations. Missense mutations in exon 5, 7, or 8 were detected in 9 of 20 immunopositive pairs and in 1 of 6 immunonegative pairs. A marked heterogeneity of mutations in primary prostate cancer was apparent. The frequency of p53 mutations was greater in the metastases than in the primary tumors. In three immunopositive pairs, the same p53 mutation was demonstrated at a low frequency in the primary tumor but was demonstrated at a greater frequency in the metastasis, indicating relatively limited clonal expansion of cells harboring specific p53 mutations in the primary tumor, yet significant clonal growth at metastatic sites as determined by this novel method.

Muscarinic receptors in diabetic rat prostate.

To investigate the effects of experimentally-induced diabetes on prostatic muscarinic cholinergic receptors, the binding characteristics of [3H]quinuclidinyl benzilate ([3H]QNB) to prostatic membrane particulates were examined in four groups of rats: control, diabetic, diabetic insulin treated, and diabetic myo-inositol treated. Diabetes was induced by i.v. injection of streptozotocin (STZ), 65 mg/kg. Diabetic and diabetic myo-inositol-treated rats had hyperglycemia, hypoinsulinemia, glucosuria, polydipsia, and polyuria as well as significantly smaller prostates and lower body weights compared to control and diabetic insulin-treated animals. The densities of muscarinic receptors (Bmax) as determined by saturation studies with [3H]QNB in the prostatic plasma membranes of control, diabetic, diabetic insulin-treated and diabetic myo-inositol-treated rats were 80 +/- 8, 51 +/- 5, 78 +/- 3, and 47 +/- 7 fmol/mg of protein, respectively. [3H]QNB binding to muscarinic receptors was inhibited by muscarinic antagonists with the following rank order of Ki values: atropine much less than pirenzepine less than AF-DX 116. The pharmacological profile of the muscarinic receptors was similar in all groups examined and was consistent with the predominance of the M3 muscarinic receptor subtype in prostatic membrane particulates. Our data indicate that STZ-induced diabetes caused a variety of abnormalities including a down-regulation in the density of M3 muscarinic receptors in the rat prostate and that insulin, but not myo-inositol could prevent the development of these abnormalities.

[Female urethral diverticulum. Report of a case]. / Divertículo uretral femenino. A propósito de un caso.

PURPOSE: We describe the successful repair of a large and complex urethral diverticulum in a female by transvaginal approach. Epidemiology, diagnostic methods, treatments and complications of female urethral diverticula are reviewed. PATIENTS AND METHODS: A 35-year-old woman with a history of postvoid dribbling, dyspareunia and recurrent urinary tract infections for 4 months was referred. Magnetic resonance imaging demonstrated two fluido-filled collections in the pelvis of 3.5 and 1 cm in size respectively which may be a very large and complex diverticulum, however, Bartholin gland cyst could not be rule out. Cystourethroscopy revealed a urethral diverticulum at 10 mm from the bladder neck with two ostia. It was performed transvaginal diverticulectomy and an anterior vaginal wall flap was placed. The published literature on female urethral diverticula was identified using a Pubmed Medline search and analysed. RESULTS: Convalescence was unremarkable. Suprapubic cystostomy tube was removed 2 weeks after surgery. The patient regained normal voiding. In the published literature there are no agreement neither in the diagnostic nor in the surgical techniques for female urethral diverticula. CONCLUSIONS: Urethral diverticula are diagnosed with increasing frequency. However, this entity continues to be overlooked because the symptoms may mimic other disorders. Cystourethroscopy, retrograde urethrograme using a double balloon catheter and recently magnetic resonance imaging may diagnose this disease. The cure rate of urethral diverticula with appropriate surgical management has a range of 86-100%. Complete excision through the anterior vaginal wall is the most successful treatment modality with minimum postoperative complications.

[Acute urinary retention secondary to clear cell adenocarcinoma of the urethra]. / Rétention urinaire aiguë secondaire à un adénocarcinome à cellules claires de l'urèthre.

The authors report a case of primary clear cell cancer of the urethra in a woman presenting with acute urinary retention. The diagnosis was based on cystoscopy and confirmed by histological examination of urethral biopsies. Treatment consisted of urethrocystectomy with creation of an "Indiana pouch". The pathological stage was T3N2M0 [1]. Three months postoperatively, the patient presented with inguinal lymph node metastases. She was treated with 3 courses of chemotherapy (mitomycin and 5-fluorouracil) combined with radiotherapy. With a follow-up of 10 months, the patient is still alive and inguinal lymph nodes have regressed. This case report emphasizes the rarity of this histological type and describes the management of urinary retention in a woman when an underlying specific disease is suspected.

International standards to document remaining autonomic function after spinal cord injury.

STUDY DESIGN: Experts opinions consensus. OBJECTIVE: To develop a common strategy to document remaining autonomic neurologic function following spinal cord injury (SCI). BACKGROUND AND RATIONALE: The impact of a specific SCI on a person's neurologic function is generally described through use of the International Standards for the Neurological Classification of SCI. These standards document the remaining motor and sensory function that a person may have; however, they do not provide information about the status of a person's autonomic function. METHODS: Based on this deficiency, the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS) commissioned a group of international experts to develop a common strategy to document the remaining autonomic neurologic function. RESULTS: Four subgroups were commissioned: bladder, bowel, sexual function and general autonomic function. On-line communication was followed by numerous face to face meetings. The information was then presented in a summary format at a course on Measurement in Spinal Cord Injury, held on June 24, 2006. Subsequent to this it was revised online by the committee members, posted on the websites of both ASIA and ISCoS for comment and re-revised through webcasts. Topics include an overview of autonomic anatomy, classification of cardiovascular, respiratory, sudomotor and thermoregulatory function, bladder, bowel and sexual function. CONCLUSION: This document describes a new system to document the impact of SCI on autonomic function. Based upon current knowledge of the neuroanatomy of autonomic function this paper provides a framework with which to communicate the effects of specific spinal cord injuries on cardiovascular, broncho-pulmonary, sudomotor, bladder, bowel and sexual function.

Postirradiation vesicovaginal fistula completely resolved with conservative treatment.

Postirradiation vesicovaginal fistulae (VVF) pose a great challenge for the urologist. The poorly vascularized radiated tissue surrounding the fistula impairs healing and makes operative repair technically demanding. Conservative treatment for postirradiation VVF is considered inappropriate, and to our knowledge has never previously been described. We present a case of a woman with postirradiation VVF that was resolved after transurethral coagulation and 3 weeks of catheterization.

Reconstruction and undiversion of the short or severely dilated ureter: the antireflux ileal nipple revisited.

PURPOSE: Patients undergoing reconstruction of short or severely dilated aperistaltic ureters are at significant risk for mechanical or functional obstruction and reflux, particularly when the ureters are being reimplanted into gastric or intestinal segments. For this problem we describe a simple handsewn, "stapleless" antireflux ileal nipple, which serves as a useful bridge between a short ureter and the bladder or reservoir. MATERIALS AND METHODS: A total of 12 patients, 4 to 42 years old (mean age 19), 9 with severely dilated and 3 with short ureters have received the stapleless antireflux ileal nipple as part of various reconstructive efforts. Briefly, a 12 to 15 cm. segment of ileum is isolated and the mesentery is stripped from the middle 8 cm. of the isolated segment, preserving the blood supply to the proximal and distal 2 cm. of ileum. Intussusception is created and maintained with multiple (5 to 7) circumferential rows of 4 to 6 interrupted seromuscular stitches of 3-zero silk. RESULTS: Mean followup is 27.5 months (range 6 to 60). Upper tract dilatation has stabilized or improved in all patients, deteriorating temporarily in 1 who had distal nipple stenosis. All patients underwent followup video urodynamic studies, which demonstrated no reflux. Nipple related complications included nipple stenosis in 1 patient and dessusception in another. Both complications were corrected without sequelae. Ureteroileal stenosis or stone formation has not occurred. CONCLUSIONS: The stapleless antireflux ileal nipple is safe and reliable in preventing reflux. It is a versatile adjunct to urinary reconstruction in patients with short or severely dilated, aperistaltic ureters in whom the alternative of a tapered reimplantation into a segment of bowel or stomach poses a significant complication threat.

Current investigations and treatment of interstitial cystitis.

Interstitial cystitis (IC) is a chronic condition characterized by a constellation of symptoms such as urinary frequency, nocturia, urinary urgency, suprapubic pressure, and bladder and pelvic pain. Since its original description, the etiology of the disorder has remained unknown despite intense investigations. The International Cystitis Association (ICA) and the National Institutes of Arthritis, Diabetes, Digestive and Kidney Diseases (NIDDK) have been instrumental in supporting the United States Interstitial Database (ICDB) and foster research to study the disorder. The NIDDK developed criteria to ensure that all groups of patients treated would be relatively comparable. However, many patients who would be clinically considered to have IC do not fulfill all the NIDDK criteria. Many clinical criteria for the diagnosis of IC, such as the presence of glomerulations and the intravesical potassium chloride test, are being challenged. The epidemiology of the disorder is not well established, but there are an estimated 700,000 cases of IC in the United States. Numerous pathophysiologic mechanisms have been proposed, but none have been proven. There is no representative animal model of IC. Both the oral and intravesical treatments of IC are noncurative, and few are based on a plausible mechanism or scientific evidence. Surgical treatment should be considered with extreme caution; it is the last therapeutic option because failure rate can be substantial.

Effect of insulin and dietary myoinositol on muscarinic receptor alterations in diabetic rat bladder.

Previous studies from our laboratory demonstrated that there is an up-regulation of muscarinic receptor density in the bladder dome of the 8-wks diabetic rat compared to control. To determine whether the changes observed in receptor density can be corrected by insulin or dietary myoinositol, five groups of rats were maintained for eight weeks: control (C), diabetic (D), diabetic insulin-treated (DI), diabetic myoinositol-treated (DMI), and control myoinositol-treated (CMI). Diabetes was induced by i.v. injection of 65 mg./kg. of streptozotocin. D and DMI animals were smaller, had higher serum glucose and lower serum insulin levels, higher water intakes and urine outputs, and larger bladder domes than the other groups. The density of the muscarinic receptors measured by radioligand receptor binding assays using [3H]quinuclidinyl benzilate were (in fmol./mg. protein): C, 88 +/- 13; D, 176 +/- 19; DI, 94 +/- 5; DMI, 158 +/- 8; CMI, 112 +/- 10. These data indicate that insulin, but not myoinositol treatment normalized diabetes induced abnormalities observed in the general features of streptozotocin-injected rats and prevented the diabetic-induced upregulation of bladder dome muscarinic receptors.

Beta adrenergic receptor alterations in diabetic rat prostate: effects of insulin and dietary myoinositol.

As sexual dysfunction is a well-recognized manifestation of diabetes mellitus and as the function of the prostate, a major accessory organ in the male reproductive system, is regulated by the autonomic nervous system, we studied beta adrenergic receptors in the prostate of streptozotocin-induced diabetic rats, using radioligand receptor binding techniques. Four groups of rats were maintained for 8 weeks: controls, diabetics, insulin-treated diabetics, and myoinisitol-treated diabetics. The diabetic and myoinisitol-treated diabetic animals were smaller, had higher blood glucose levels, higher water intake and urine output, smaller prostates, and lower serum insulin levels than the other groups. Saturation experiments with [3H]dihydroalprenolol showed that the induction of diabetes decreased the density of beta adrenergic receptors in prostatic membrane particulates. Inhibition studies with selective beta adrenergic antagonists demonstrated that these receptors were of the beta 2 subtype. Furthermore, insulin but not myoinositol treatment normalized blood glucose and insulin levels, maintained normal prostate and body weight-gain, and prevented the decrease in the density, i.e., down-regulation, of the prostatic beta adrenergic receptors.

Fixed and dynamic urethral compression for the treatment of post-prostatectomy urinary incontinence: is history repeating itself?

PURPOSE: We reviewed the evolution of appliances and devices used for treating post-prostatectomy urinary incontinence. MATERIALS AND METHODS: We used the MEDLINE to search the literature from 1966 to March 2000 and then manually searched bibliographies to identify studies that our initial search may have missed. RESULTS: The evolution of treatment for post-prostatectomy urinary incontinence may be traced back to the 18th century. Two main schools of thoughts simultaneously evolved. The first fixed urethral compression devices were constructed to enable urethral obstruction by fixed resistance. This outlet resistance allows voiding after intra-abdominal and intravesical pressure is elevated but it is sufficient to prevent leakage between urinations. The other school of thought preferred creation of dynamic urethral compression in which outlet resistance is not fixed but may be decreased when voiding is desired or elevated between urinations. Therapeutic fixed and dynamic urethral compression interventions may be further divided into external or internal compressive devices or procedures. External fixed compression devices may be traced back to antiquity. A penile clamp, similar to the later Cunningham clamp, and a truss designed to compress the urethra by external perineal compression were presented in the Heister textbook of surgery, Institutiones Chirurgicae, as early as 1750. Dynamic compressive devices applied externally were developed much later, such as the first artificial urinary sphincter, described by Foley, in 1947 and the Vincent apparatus, described in 1960. The modern era of fixed urethral compression began in 1961 with Berry. Acrylic prostheses impregnated with bismuth to allow radiographic visualization were produced in various shapes and sizes, and used to compress the urethra against the urogenital diaphragm. In 1968 the University of California-Los Angeles group under the direction of Kaufman began to use cavernous crural crossover to compress the bulbous urethra (Kaufman I). Later 2 other modifications were described, including approximation of the crura in the midline using a polytetrafluoroethylene mesh tape (Kaufman II) and an implantable silicone gel prosthesis (Kaufman III). With the advent of the artificial urinary sphincter pioneered by Scott in 1973 interest in passive urethral compression disappeared in favor of the implantation of an inflatable circumferential prosthetic sphincter. Recently there has been a trend back to passive urethral compression. Synthetic bolsters have been described that passively compress the bulbar urethra to achieve urinary incontinence after radical prostatectomy. CONCLUSIONS: Much creativity has been dedicated to solve the complex and challenging problem of post-prostatectomy urinary incontinence. Devices used for treating this condition may be grouped according to the mechanism of action and how they are applied. Passive urethral compression, long abandoned in favor of dynamic implantable sphincters, has reemerged. Further research in this field may determine which school of thought may provide the best solution for treating post-prostatectomy urinary incontinence.

Collaboration and practice patterns among urologists and gynecologists in the treatment of urinary incontinence and pelvic floor prolapse: a survey of the International Continence Society members.

Both urologists and gynecologists are involved in the care of women with urinary incontinence (UI) and pelvic floor prolapse (PFP). This study was designed to examine the differences among urologists and gynecologists who treat UI and PFP, and to characterize the collaboration between them. A 14-question survey was mailed to the International Continence Society (ICS) members who are urologists or gynecologists. Questions dealt with professional training, type of practice, volume of UI and PFP procedures, preferred procedures for various types of UI and PFP, and the type and extent of collaboration. Of the 666 urologists and gynecologists to whom the questionnaire was sent, 229 responded (34.4% response rate). Among them, 63.7% were urologists and 36.2% were gynecologists. Collaboration in the operating room was reported by 140 responders (50.7%) and was significantly correlated with the specialty, and with the country of practice, with P values of 0.004, and 0.004, respectively. Collaboration in the operating room was reported mainly in procedures for the correction of vaginal vault prolapse or enterocele, and hysterectomy. It was not statistically correlated with the time dedicated to UI and PFP, the volume of surgeries performed, UI and PFP fellowship training, university hospital affiliation, and years in practice. Reasons for not collaborating in the operating room included familiarity with all or most of the anti-incontinence and pelvic floor reconstruction procedures (44.5%), unavailability of the other professional (6.1%), and reimbursement problems (3.1%). While urologists and gynecologists do collaborate extensively in clinical research and diagnosis of challenging cases, surgical collaboration is limited to procedures traditionally performed by gynecologists. Future training programs exposing trainees to both fields of expertise may enable better ground for collaboration and improved care for women with UI and PFP.

4-Defect repair of grade 4 cystocele.

PURPOSE: The 4-defect repair of grade 4 cystocele corrects discrete and severe deficiencies of vesicourethral support. We describe this technique used during pelvic reconstruction in 130 women. MATERIALS AND METHODS: During a 3-year period 130 patients (age range 35 to 96 years) underwent repair of grade 4 cystocele using the 4-defect repair technique. Cystocele repair had been performed in 60 patients (46%) and hysterectomy had been performed in 85 (65%). A "goalpost incision" is used in the vaginal wall to facilitate separation of the wall from underlying perivesical fascia, entry into the retropubic space, and exposure of the urethropelvic ligament, cardinal ligament and perivesical fascia. The 4 polypropylene sutures are used to provide an anterior vaginal wall sling which is modified to incorporate perivesical fascia and cardinal ligaments. Central defect repair is achieved by approximation of the cardinal ligaments and midline plication of the perivesical fascia over absorbable mesh. RESULTS: A total of 112 patients were available for followup which ranged from 6 to 42 months (mean 21). Repair of grade 4 cystocele was accompanied by other transvaginal repairs in 94 patients (83%), including rectocele repair in 81, hysterectomy in 22 and enterocele repair in 31. Of the patients 92% had excellent objective and subjective results for anatomical cystocele repair. Of the patients with preoperative stress urinary incontinence 90% had excellent or good subjective results. De novo urge incontinence was seen in 7% of patients. CONCLUSIONS: The 4-defect repair technique relies on anatomical restoration of 4 distinct deficiencies of pelvic support and is highly effective for relief of symptoms of grade 4 cystocele.

Artificial urinary sphincter for post-radical prostatectomy urinary incontinence: long-term subjective results.

PURPOSE: Incontinence affects between 3% and 60% of patients after radical prostatectomy. Insertion of an artificial urinary sphincter is a mainstay therapeutic option available to these patients. We assessed patient satisfaction, outcome and complications long after artificial urinary sphincter implantation. MATERIALS AND METHODS: From a data bank of 131 patients who underwent artificial urinary sphincter prosthesis insertion we identified 71 with a mean age of 72 years who had also undergone radical prostatectomy and were available for evaluation. This group included 29 patients (40.8%) who received an earlier version of the AMS-800 (American Medical Systems, Minnetonka, Minnesota) and 42 (59.2%) who received the newer narrow back cuff device. Information on surgical procedures and followup were obtained from a computerized database. Patients were also contacted by an impartial reviewer who administered a standard telephone questionnaire on the degree of continence, complications, other means used to help with urinary continence, proficiency in device operation and satisfaction. RESULTS: At a mean followup of 7.7 years (range 0.5 to 16) 19 patients (27%) used 0, 23 (32%) used 1, 11 (15%) used 1 to 3 and 18 (25%) used more than 3 daily, while 1 used an external catheter. Surgical revision in 21 cases (29%) was required due to mechanical failure in 18 (25%), device erosion in 3 (4%) and infection in 1 (1.4%). The need for revision correlated significantly with the design of the sphincter (p = 0.005). Only 7 of the 42 patients in whom a narrow cuff AMS-800 was implanted needed revision versus 18 of the 23 with a previous design. Mean time to revision was 2.5 years (range 0.5 to 8). The device was removed in 2 cases (2.8%). Of the patients 41 (58%) are very satisfied, 14 (19%) are satisfied and 16 (23%) are unsatisfied with the device. The degree of satisfaction correlated with the number of pads used (p = 0.0005) and sphincter design (0.028) but not with the number of surgical revisions (p = 0.521) or patient age. CONCLUSIONS: The artificial urinary sphincter is a viable treatment option for post-radical prostatectomy incontinence with a high rate of continence and satisfaction for a long period after the procedure. Patients should be informed that complications necessitating device revision and explantation may appear late in followup. A standard definition of treatment success and studies of homogenous groups of patients with an artificial urinary sphincter would enable better understanding and patient education in the future.

Refashioned short bowel segments for the construction of catheterizable channels (the Monti procedure): early clinical experience.

PURPOSE: We report the early results of a new surgical procedure to construct a catheterizable stoma from a small segment of bowel according to the Monti technique. MATERIALS AND METHODS: Since November 1996, 4 male and 4 female patients with a mean age of 14 years have undergone the Monti procedure in association with other reconstructive efforts. Indications included the unavailability of appendix because of concomitant ACE Malone appendicocecostomy in 2 patients, atretic appendixes in 3, previous appendectomy in 2 and technical difficulties during appendix isolation in 1. In no patient was small bowel used instead of a suitable appendix. Other simultaneous surgical procedures included bladder augmentation in 4 patients in whom the bowel tube and patch for augmentation were created with the same mesenteric pedicle (ileum in 3 and sigmoid colon in 1). RESULTS: Followup ranged from 3 to 11 months (mean 7). No patient has had difficulty with catheterization or any other problems related to the stoma. In 2 patients stomal leakage required additional procedures and pharmacological manipulation. CONCLUSIONS: The appendiceal Mitrofanoff procedure remains the technique of choice for the construction of catheterizable continent stomas. In the absence of a suitable appendix a catheterizable bowel conduit based on the Monti technique appears to be the best alternative in our early experience. The short segment of bowel required for conduit construction, excellent blood supply throughout its length, and the possibility of developing the tube and bowel patch for simultaneous augmentation from the same pedicle are some of the clear advantages of this technique.

Grading pelvic prolapse and pelvic floor relaxation using dynamic magnetic resonance imaging.

OBJECTIVES: With significant vaginal prolapse, it is often difficult to differentiate among cystocele, enterocele, and high rectocele by physical examination alone. Our group has previously demonstrated the utility of magnetic resonance imaging (MRI) for evaluating pelvic prolapse. We describe a simple objective grading system for quantifying pelvic floor relaxation and prolapse. METHODS: One hundred sixty-four consecutive women presenting with pelvic pain (n = 39) or organ prolapse (n = 125) underwent dynamic MRI. The "H-line" (levator hiatus) measures the distance from the pubis to the posterior anal canal. The "M-line" (muscular pelvic floor relaxation) measures the descent of the levator plate from the pubococcygeal line. The "O" classification (organ prolapse) characterizes the degree of visceral prolapse beyond the H-line. RESULTS: The image acquisition time was 2.5 minutes per study. Each study cost $540. In the pain group, the H-line averaged 5.2 +/- 1.1 cm versus 7.5 +/- 1.5 cm in the prolapse group (P <0.001). The M-line averaged 1.9 +/- 1.2 cm in the pain group versus 4.1 +/- 1.5 cm in the prolapse group (P <0.001). Incidental pelvic pathologic features were commonly noted, including uterine fibroids, ovarian cysts, hydroureter, urethral diverticula, and foreign body. CONCLUSIONS: The HMO classification provides a straightforward and reproducible method for staging and quantifying pelvic floor relaxation and visceral prolapse. Dynamic MRI requires no patient preparation and is ideal for the objective evaluation and follow-up of patients with pelvic prolapse and pelvic floor relaxation. MRI obviates the need for cystourethrography, pelvic ultrasound, or intravenous urography and has become the study of choice at our institution for evaluating the female pelvis.

Life-threatening anaphylactoid reaction associated with indigo carmine intravenous injection.

Indigo carmine (sodium indigotindisulfonate), a blue dye, has been widely used by surgeons to identify and to examine the urinary tract and is considered biologically inert and extremely safe. We present a case of severe life-threatening anaphylactoid reaction followed by cardiac arrest associated with intravenous indigo carmine injection.

Effects of experimental diabetes on biochemical and functional characteristics of bladder muscarinic receptors.

Bladder dysfunction is a common complication of diabetes mellitus and is attributed in part to peripheral neuropathy. We investigated the effects of experimental diabetes on muscarinic receptors in rat bladder smooth muscle, 2, 4 and 8 weeks after i.v. injection of 65 mg/kg of streptozotocin. At all time points, diabetic animals had a lower body weight, higher serum glucose levels and reduced serum insulin levels than age-matched controls. Diabetic animals had a markedly increased urine output and significant enlargement of the bladder dome. The amount of muscarinic receptor labeled with [3H]quinuclidinyl benzylate (QNB) was higher in the bladder dome of diabetic animals than control animals, whereas the affinity of the labeled antagonist for its binding sites was similar in both groups. Muscarinic agonists and antagonists inhibited [3H]QNB binding with similar inhibitory constants (Ki) in control and diabetic dome. The rank order of Ki values in inhibition of [3H]QNB binding by muscarinic agonists and antagonists: atropine less than acetylcholine less than carbachol less than AF-DX 116 = pirenzepine less than bethanechol, is consistent with the presence of M2 muscarinic receptors in the bladder dome. In functional studies, muscarinic agonists induced a larger contractile response in bladder dome muscle strips from 8-week-diabetic animals than from controls. ED50 values were similar in control and treated groups, with the rank order of ED50 values being in good agreement with the Ki values obtained from receptor binding studies, i.e., acetylcholine less than carbachol less than bethanechol. These data show a direct correlation between the diabetes-induced biochemical and functional alterations in muscarinic receptor properties of rat bladder.

Genetic and molecular analysis of spontaneous respiratory deficient (res-) mutants of Escherichia coli K-12.

Respiratory deficient (res-) mutants of E. coli are slow growing microcolonial, anaerobic, catalase and benzidine negative strains whose broad phenotypic alteration may result from pleiotropic mutations in genes of the hemin biosynthetic pathway. They are easily recovered from platings of sensitive cells on concentrations of gentamicin higher than the minimal inhibitory concentration. These mutants show a dramatic change in their biochemical diagnostic profile resulting primarily from deficiencies in the active transport mechanisms of the cell. Using well-marked F- and Hfr strains, 157 mutants were analyzed from 3 different parent strains; all but 2 resulted from mutations in 3 loci of the hemin biosynthetic pathway. Of these a marked skew to hemB- mutations was seen, with more than 80% mapping there. The possibility that this hot spot resulted from transpositional activity was tested by Southern hybridization of EcoRI digests of the chromosomal DNA, using as a probe, a 2.8-kb fragment containing the hemB gene. The WT and other hemB+ control strains contained a 14.6-kb fragment. Of 18 hemB strains tested, 14 showed deletion and insertion mutations which fell into four classes based on the variation in the size of the fragment or on the absence of hybridization. The latter resulted from complete deletion of the hemB gene. An increase in fragment size from 1.5-kb to 3.4-kb was observed in some of the strains.