Management of overactive bladder: consensus statements from the Hong Kong Urological Association and the Hong Kong Geriatrics Society.

Overactive bladder (OAB) is a common urological disease with a high prevalence in older adult populations. Antimuscarinic drugs have been the most common treatment for OAB for more than a decade, but their anticholinergic side-effects and potential impact on cognitive function among older patients are usually underestimated. This consensus aimed to provide practical recommendations concerning OAB management, with a particular emphasis on older patients. A joint consensus panel was formed by representatives of the Hong Kong Urological Association and the Hong Kong Geriatrics Society. Literature searches regarding OAB and its management were performed in PubMed and Ovid. Several working meetings were held to present and discuss available evidence, develop consensus statements, and vote for the statements. A modified Delphi method was used in this consensus process. To address questions regarding various aspects of OAB, 29 consensus statements were proposed covering the following areas: diagnosis, initial assessment, non-pharmacological treatments, considerations before administration of pharmacological treatments, various pharmacological treatments, combination therapy, and surgical treatment. Twenty-five consensus statements were accepted.

Prenatal pharmacogenomics: a promising area for research.

Clinical applications of prenatal genetic screening currently focus on detection of aneuploidy and other genetic diseases in the developing fetus. Growing evidence suggests that the fetal genome may also be informative about fetal exposures through contributions to placental transport as well as placental and fetal metabolism. Possible clinical applications of prenatal pharmacogenomic screening include prospective optimization of medication selection and dosage, as well as retrospective assessment of whether a fetus was previously exposed to significant risk. Newly available noninvasive methods of prenatal genetic screening mean that relevant fetal genotypes could be made available to obstetricians for use in management of a current pregnancy. This promising area for research merits more attention than it has thus far received.The Pharmacogenomics Journal advance online publication, 10 May 2016; doi:10.1038/tpj.2016.33.

Preliminary report: Surgical outcomes following genitoplasty in children with moderate to severe genital atypia.

INTRODUCTION: Prior studies of outcomes following genitoplasty have reported high rates of surgical complications among children with atypical genitalia. Few studies have prospectively assessed outcomes after contemporary surgical approaches. OBJECTIVE: The current study reported the occurrence of early postoperative complications and of cosmetic outcomes (as rated by surgeons and parents) at 12 months following contemporary genitoplasty procedures in children born with atypical genitalia. STUDY DESIGN: This 11-site, prospective study included children aged ≤2 years, with Prader 3-5 or Quigley 3-6 external genitalia, with no prior genitoplasty and non-urogenital malformations at the time of enrollment. Genital appearance was rated on a 4-point Likert scale. Paired t-tests evaluated differences in cosmesis ratings. RESULTS: Out of 27 children, 10 were 46,XY patients with the following diagnoses: gonadal dysgenesis, PAIS or testosterone biosynthetic defect, severe hypospadias and microphallus, who were reared male. Sixteen 46,XX congenital adrenal hyperplasia patients were reared female and one child with sex chromosome mosaicism was reared male. Eleven children had masculinizing genitoplasty for penoscrotal or perineal hypospadias (one-stage, three; two-stage, eight). Among one-stage surgeries, one child had meatal stenosis (minor) and one developed both urinary retention (minor) and urethrocutaneous fistula (major) (Summary Figure). Among two-stage surgeries, three children developed a major complication: penoscrotal fistula, glans dehiscence or urethral dehiscence. Among 16 children who had feminizing genitoplasty, vaginoplasty was performed in all, clitoroplasty in nine, external genitoplasty in 13, urethroplasty in four, perineoplasty in five, and total urogenital sinus mobilization in two. Two children had minor complications: one had a UTI, and one had both a mucosal skin tag and vaginal mucosal polyp. Two additional children developed a major complication: vaginal stenosis. Cosmesis scores revealed sustained improvements from 6 months post-genitoplasty, as previously reported, with all scores reported as good or satisfied. DISCUSSION: In these preliminary data from a multi-site, observational study, parents and surgeons were equally satisfied with the cosmetic outcomes 12 months after genitoplasty. A small number of patients had major complications in both feminizing and masculinizing surgeries; two-stage hypospadias repair had the most major complications. Long-term follow-up of patients at post-puberty will provide a better assessment of outcomes in this population. CONCLUSION: In this cohort of children with moderate to severe atypical genitalia, preliminary data on both surgical and cosmetic outcomes were presented. Findings from this study, and from following these children in long-term studies, will help guide practitioners in their discussions with families about surgical management.

Urinary tract infection after voiding cystourethrogram.

BACKGROUND: Reported rates of post-procedural urinary tract infection (ppUTI) after voiding cystourethrogram (VCUG) are highly variable (0-42%). OBJECTIVE: This study aimed to determine the risk of ppUTI after cystogram, and evaluate predictors of ppUTI. STUDY DESIGN: A retrospective cohort study of children undergoing VCUG or radionuclide cystogram (henceforth 'cystogram') was conducted. Children with neurogenic bladder who underwent cystogram in the operating room and without follow-up at the study institution were excluded. Incidence of symptomatic ppUTI within 7 days after cystogram was recorded. Predictors of ppUTI were evaluated using univariate statistics. RESULTS: A total of 1108 children (54% female, median age 1.1 years) underwent 1203 cystograms: 51% were on periprocedural antibiotics, 75% had a pre-existing urologic diagnosis (i.e., vesicoureteral reflux (VUR) or hydronephrosis; not UTI alone), and 18% had a clinical UTI within 30 days before cystogram. Of the cystograms, 41% had an abnormal cystogram and findings included VUR (82%), ureterocele (6%), and diverticula (6%). Twelve children had a ppUTI (1.0%; four girls, five uncircumcised boys, three circumcised boys; median age 0.9 years). Factors significantly associated with diagnosis of a ppUTI (Summary fig.) included: pre-existing urologic diagnosis prior to cystogram (12/12, 100% of patients with ppUTI), abnormal cystogram results (11/12, 92%), and use of periprocedural antibiotics (11/12, 92%). All 11 children with an abnormal cystogram had VUR ≥ Grade III. However, among all children with VUR ≥ Grade III, 4% (11/254) had a ppUTI. DISCUSSION: This is the largest study to date that has examined incidence and risk factors for ppUTI after cystogram. The retrospective nature of the study limited capture of some clinical details. This study demonstrated that the risk of ppUTI after a cystogram is very low (1.0% in this cohort). Having a pre-existing urologic diagnosis such as VUR or hydronephrosis was associated with ppUTI; therefore, children with moderate or high-grade VUR on cystogram may be at highest risk. Development of ppUTI after cystogram also highlighted the potential for a delay in diagnosis or oversight of a healthcare-associated infection due to several factors: 1) cystograms may be ordered, performed/interpreted, and followed up by multiple different providers; and 2) such infections are not captured by traditional healthcare-associated infection surveillance strategies. CONCLUSIONS: The risk of ppUTI after a cystogram is very low. Only children with pre-existing urologic diagnoses developed ppUTI in this study. This study's findings suggest that children undergoing a cystogram should not be given peri-procedural antibiotic prophylaxis for the sole purpose of ppUTI prevention.

Lipomyelomeningocele for the urologist: Should we view it the same as myelomeningocele?

INTRODUCTION: The primary urologic objectives for lipomyelomeningocele (LMM) and myelomeningocele (MM) are preserving renal integrity and achieving continence. Due to this common ground, LMM and MM are urologically treated the same. However, unlike MM, LMM may present with no evident functional concerns. Indications for and timing of tethered cord release (TCR) in LMM are therefore controversial. Long-term urologic outcomes are not well defined. OBJECTIVE: Expectations for continence and potential for intermittent catheterization (CIC) following TCR in LMM are important for realistically counseling families regarding future needs. The present study aimed to identify prognostic factors for continence and need for CIC in LMM. STUDY DESIGN: The present study retrospectively identified 143 patients from the multidisciplinary clinic who underwent TCR for LMM between 1995 and 2010. Concomitant anorectal/genitourinary anomalies, filar lipoma, fatty filum, previous TCR, and follow-up <1 year were excluded. Analysis was limited to those toilet trained or aged ≥6 years at latest follow-up. Lipomyelomeningocele was classified as dorsal, distal, transitional or chaotic. Pre- and post-TCR urologic status was assessed. Ability to achieve urinary continence, with or without CIC, was the primary outcome, and need for CIC was the secondary outcome of interest. RESULTS: A total of 56 patients met inclusion criteria. Median age at TCR was 4.4 months (range 1.0-224.0) with a median follow-up of 10.7 years (range 1.3-19.1); 68% were asymptomatic at presentation. Clinical symptoms were urologic in 7%. At the latest follow-up, 86% of patients were continent spontaneously or with CIC (Summary Fig.). Of the four patients who presented with urologic symptoms, all were continent, but three required CIC. Overall, 23% of patients required CIC. Median age at CIC initiation was 7.6 years (range 1.6-17.4). Long-term continence was not associated with any demographic, anatomic, surgical or functional variable. Need for CIC at latest follow-up was associated with symptomatic presentation, partial TCR, transitional lipoma, and high-risk pre-operative urodynamics. DISCUSSION: In this series of primary TCR for LMM, where 93% of patients were urologically asymptomatic before TCR, prospects for continence were excellent. No studied parameter clearly impacted continence; however, need for CIC was associated with multiple variables. CONCLUSIONS: Clear predictors for continence after TCR will require additional long-term patient outcomes. Families can anticipate 23% likelihood of CIC, which is considerably less than in MM, but long-term urologic follow-up is still strongly recommended.

Prospective assessment of cosmesis before and after genital surgery.

INTRODUCTION: Little data exist about the surgical interventions taking place for children with disorders of sex development (DSD). Most studies that have evaluated cosmetic outcomes after genitoplasty have included retrospective ratings by a physician at a single center. OBJECTIVE: The present study aimed to: 1) describe frequency of sex assignment, and types of surgery performed in a cohort of patients with moderate-to-severe genital ambiguity; and 2) prospectively determine cosmesis ratings by parents and surgeons before and after genital surgery. STUDY DESIGN: This prospective, observational study included children aged <2 years of age, with no prior genitoplasty at the time of enrollment, moderate-to-severe genital atypia, and being treated at one of 11 children's hospitals in the United States of America (USA). Clinical information was collected, including type of surgery performed. Parents and the local pediatric urologist rated the cosmetic appearance of the child's genitalia prior to and 6 months after genitoplasty. RESULTS: Of the 37 children meeting eligibility criteria, 20 (54%) had a 46,XX karyotype, 15 (40%) had a 46,XY karyotype, and two (5%) had sex chromosome mosaicism. The most common diagnosis overall was congenital adrenal hyperplasia (54%). Thirty-five children had surgery; 21 received feminizing genitoplasty, and 14 had masculinizing genitoplasty. Two families decided against surgery. At baseline, 22 mothers (63%), 14 fathers (48%), and 35 surgeons (100%) stated that they were dissatisfied or very dissatisfied with the appearance of the child's genitalia. Surgeons rated the appearance of the genitalia significantly worse than mothers (P < 0.001) and fathers (P ≤ 0.001) at baseline. At the 6-month postoperative visit, cosmesis ratings improved significantly for all groups (P < 0.001 for all groups). Thirty-two mothers (94%), 26 fathers (92%), and 31 surgeons (88%) reported either a good outcome, or they were satisfied (see Summary Figure); there were no significant between-group differences in ratings. DISCUSSION: This multicenter, observational study showed surgical interventions being performed at DSD centers in the USA. While parent and surgeon ratings were discordant pre-operatively, they were generally concordant postoperatively. Satisfaction with postoperative cosmesis does not necessarily equate with satisfaction with the functional outcome later in life. CONCLUSION: In this cohort of children with genital atypia, the majority had surgery. Parents and surgeons all rated the appearance of the genitalia unfavorably before surgery, with surgeons giving worse ratings than parents. Cosmesis ratings improved significantly after surgery, with no between-group differences.

HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, is overexpressed in colon carcinoma.

Using the palindromic PCR-cDNA display method, we have cloned a novel gene overexpressed by human colon carcinoma relative to normal colon. Among normal tissues examined, only testis expresses it at a high level. Sequence analysis revealed its extensive homology with checkpoint genes rad17 of Schizosaccharomyces pombe and RAD24 of Saccharomyces cerevisiae. This novel gene designated as hRad17 is localized to chromosome 5q12,13.1, a region known to be deleted in a variety of human cancers. Promoter region and one pseudogene of hRad17 have been identified. Whereas the increased expression of hRad17 by human colon carcinomas may be related to the known resistance of these cells to DNA-damaging agents during therapy, the deletion of hRad17 in a variety of cancers may predispose them to increased rate of mutation and heightened sensitivity to DNA-damaging agents, including radiation and anticancer drugs.

Repair of megameatus: a modified approach.

OBJECTIVE: To demonstrate surgical reconstruction of a megameatus variant of hypospadias by using a modified, patient-specific approach. METHODS: An 8-month-old male had a megameatus, which was discovered after newborn circumcision. In repair of megameatus, it is important to recognize the full extent to which the distal urethra is widened, in order to avoid inadvertent urethrotomy during mobilization of the glans wings and skin immediately proximal to the glans. In this case, a small wedge of tissue was excised from the ventral aspect of the urethra, and a midline relaxing incision of the urethral plate was made. Standard principles of hypospadias repair should be followed, with tension-free urethral tubularization, coverage of the neourethra with well-vascularized tissue, and adequate mobilization of the glans wings to allow midline reconstruction without compression of the underlying neourethra. RESULTS: There were no perioperative or postoperative complications in this case. The urethral meatus was positioned near the tip of the glans penis, and there was no evidence of meatal stenosis or urethrocutaneous fistula at 5-months follow-up. CONCLUSION: Each case of megameatus is unique, and a variety of surgical techniques can be used in formulating an approach that achieves optimal cosmetic and functional outcomes.

Successful term pregnancy in an intestine-pancreas transplant recipient with chronic graft dysfunction and parenteral nutrition dependence: a case report.

Pregnancy after solid organ transplantation is becoming more common, with the largest recorded numbers in renal and liver transplant recipients. Intestinal transplantation is relatively new compared to other solid organs, and reports of successful pregnancy are far less frequent. All pregnancies reported to date in intestinal transplant recipients have been in women with stable graft function. The case reported here involves the first reported successful term pregnancy in an intestine-pancreas transplant recipient with chronic graft dysfunction and dependence on both transplant immunosuppression and parenteral nutrition (PN) at the time of conception. Pregnancy was unplanned and unexpected in the setting of chronic illness and menstrual irregularities, discovered incidentally on abdominal ultrasound at approximately 18 weeks' gestation. Rapamune was held, tacrolimus continued, and PN adjusted to maintain consistent weight gain. A healthy female infant was delivered vaginally at term. Medical complications during pregnancy included anemia and need for tunneled catheter replacements. Ascites and edema were improved from baseline, with recurrence of large volume ascites shortly after delivery. Successful pregnancy is possible in the setting of transplant immunosuppression, chronic intestinal graft dysfunction, and long-term PN requirement, but close monitoring is required to ensure the health of mother and child.

The mu-opioid receptor gene-dose dependent reductions in G-protein activation in the pons/medulla and antinociception induced by endomorphins in mu-opioid receptor knockout mice.

There appear to be different relationships between mu-opioid receptor densities and the acute and neuroadaptive mu-opioid agonist-induced responses of the multiple opioid neuronal systems, including important pons/medulla circuits. The recent success in creating mu-opioid receptor knockout mice allows studies of mu-opioid agonist-induced pharmacological and physiological effects in animals that express no, one or two copies of the mu-opioid receptor gene. We now report that the binding of mu-opioid receptor ligand, [3H][D-Ala2,NHPhe4,Gly-ol]enkephalin to membrane preparations of the pons/medulla was reduced by half in heterozygous mu-opioid receptor knockout mice and eliminated in homozygous mu-opioid receptor knockout mice. The endogenous mu-opioid agonist peptides endomorphin-1 and -2 activate G-proteins in the pons/medulla from wild-type mice in a concentration-dependent fashion, as assessed using [35S]guanosine-5'-o-(3-thio)triphosphate binding. This stimulation was reduced to half of the wild-type levels in heterozygous mice and eliminated in homozygous knockout mice. The intracerebroventricular injection of either endomorphin-1 or endomorphin-2 produced marked antinociception in the hot-plate and tail-flick tests in wild-type mice. These antinociceptive actions were significantly reduced in heterozygous mu-opioid receptor knockout mice, and virtually abolished in homozygous knockout mice. The mu-opioid receptors are the principal molecular targets for endomorphin-induced G-protein activation in the pons/medulla and the antinociception caused by the intracerebroventricular administration of mu-opioid agonists. These data support the notion that there are limited physiological mu-opioid receptor reserves for inducing G-protein activation in the pons/medulla and for the nociceptive modulation induced by the central administration of endomorphin-1 and -2.

Rh isoimmunization related to amniocentesis.

We report on the incidence of Rh isoimmunization after genetic amniocentesis at our institution. In 115 Rh negative women who underwent amniocentesis and subsequently delivered Rh positive infants, there were 4 (3.4%) sensitizations before birth. This was significantly greater than the 1.5% rate of gestational sensitization found in pooled populations of women who did not undergo amniocentesis. We also noted a significant increase in the number of sensitizations that occurred before 28 weeks. The results were consistent with those of previous studies of this issue, and are discussed in relation to current policies for managing Rh negative women who have second trimester amniocentesis.

Modeling the future workforce of obstetrics and gynecology.

OBJECTIVE: To examine the current supply and distribution of obstetrician-gynecologists and project future supply under various scenarios. METHODS: A discrete actuarial supply model was developed, and practice patterns were analyzed. Supply projections under different scenarios, distributions, and practice profiles were examined. RESULTS: Women are expected to become the majority of practitioners by 2014. Continuation of current residency output will result in slow to no growth in obstetrician-gynecologist-to-female population ratios over the next 20 years. A minor (10%) reduction in specialty training would slow specialty growth over the next decade, followed by a slight reduction in supply. Services provided chiefly involve ambulatory reproductive health care, pregnancy, and surgical correction of conditions specific to the female genitourinary system. Even though the proportion of deliveries performed by midwives has increased and family practitioners have maintained their share, obstetrician-gynecologists provide the vast majority of obstetric care and virtually all services for perinatal complications. Generalist services represent relatively minor aspects of their practices. Care of the aged female population is highly fragmented among specialties; more than 50% of all aged Medicare beneficiaries who saw an obstetrician-gynecologist at least once failed to receive a majority of services from any one physician specialty. CONCLUSION: On the basis of trends in patient demographics and care patterns, obstetrician-gynecologists must resolve whether to provide more generalist office-based care, especially to the rapidly growing older female population, or to invest more intensively in surgical specialty care. The specialty's unique contributions to women's health should influence this decision.

Osteogenesis imperfecta: mode of delivery and neonatal outcome.

OBJECTIVE: To evaluate the pregnancy characteristics, methods of delivery, and neonatal outcomes of fetuses affected by osteogenesis imperfecta. METHODS: We reviewed medical records of 1016 individuals whose cells were sent to the University of Washington Collagen Diagnostic Laboratory between 1987 and 1994 for confirmation of diagnoses of osteogenesis imperfecta. Information and neonatal records were available for 167 of those pregnancies. From those we identified method(s) of prenatal detection, delivery method, and neonatal complications, including survival and acquisition of new fractures, and related them to type of delivery. RESULTS: The cesarean delivery rate was 54%, most of them (53%) for nonvertex presentation and fewer than 15% because of an antenatal diagnoses of osteogenesis imperfecta. There was an unusually high rate of breech presentation at term (37%). In infants with nonlethal forms of osteogenesis imperfecta, 24 of 59 (40%) delivered by cesarean and 17 of 53 (32%) delivered vaginally had new fractures (chi(2) =.89; P =.3). Among 55 infants with the most severe form, 24 of 31 delivered by cesarean and 21 of 24 delivered vaginally died within 2 weeks of birth. CONCLUSION: Cesarean delivery did not decrease fracture rates at birth in infants with nonlethal forms of osteogenesis imperfecta nor did it prolong survival for those with lethal forms. Prenatal diagnosis did not influence mode of delivery in most instances. Most cesarean deliveries were done for usual obstetric indications.

A prospective evaluation of a second-trimester screening test for fetal Down syndrome using maternal serum alpha-fetoprotein, hCG, and unconjugated estriol.

OBJECTIVE: To test the efficacy of a screening protocol using a combination of maternal age plus three biochemical markers--maternal serum alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (E3)--for the antenatal detection of fetal Down syndrome. METHODS: We conducted a prospective cohort study of 7718 women who underwent the triple-marker analysis between weeks 15-18 of pregnancy. A second-trimester risk for Down syndrome of 1:195 or greater was considered positive. Sensitivity, specificity, positive predictive value, and their 95% confidence intervals (CIs) were calculated. We evaluated test performance for various maternal age groups and screen-positive cutoffs, as well as the relative screening efficacies of maternal age and MSAFP, MSAFP plus hCG, and MSAFP, hCG, and unconjugated E3. RESULTS: Four hundred sixty-one of the 7718 women screened (6%) were identified as positive; 319 women chose amniocentesis, for an overall amniocentesis rate of 4.1%. Twenty of 22 pregnancies affected with Down syndrome were correctly identified, as were 7255 of 7696 unaffected pregnancies, yielding a sensitivity and specificity of 91% (95% CI 79-100%) and 94% (95% CI 93.8-94.8%), respectively. The use of maternal age plus all three analytes improved test performance compared with maternal age plus MSAFP and hCG, but either had a significantly improved detection rate compared with that for maternal age and MSAFP alone. CONCLUSION: The triple-marker screen appears to be an effective method of detecting Down syndrome pregnancies while maintaining an acceptable amniocentesis rate.

Urine levels of transforming growth factor-beta 1 in children with ureteropelvic junction obstruction.

OBJECTIVES: To determine if there are measurable quantities of transforming growth factor-beta 1 (TGF-beta 1) in the urine of children with either normal or pathologic conditions of the urinary tract, specifically vesicoureteral reflux (VUR) and ureteropelvic junction obstruction (UPJO). We also sought to determine if the urine TGF-beta level could distinguish between renal obstruction and no obstruction. METHODS: Preoperative bladder urine from consecutive patients undergoing pyeloplasty (UPJO group; n = 13), ureteral reimplantation (VUR group; n = 11), or circumcision/orchiopexy (control group; n = 19) as well as urine from the renal pelvis of the UPJO group was collected. The urine level of TGF-beta 1 was measured using a quantitative sandwich enzyme immunoassay technique. RESULTS: Urine level of TGF-beta 1 was detected in each group: control (26.6 +/- 6.3 pg/mL), reflux (22.1 +/- 9.6), UPJO-pelvic urine (82.4 +/- 19.3), UPJO-bladder urine (31.2 +/- 8.2). The urine TGF-beta 1 concentration in pelvic urine in the UPJO group was significantly higher than that in bladder urine in children in the UPJO group (p = 0.03). TGF-beta 1 concentrations were similar from the bladder of children in all three study groups (p = NS). CONCLUSIONS: Urine TGF-beta 1 is detectable in children with normal and pathologic urinary tracts. The level of this urine marker is elevated in the renal pelvis of children with UPJO compared to the level in the bladder of either obstructed or nonobstructed upper urinary tracts.

Myofascial wrap to treat intractable urinary incontinence in children.

OBJECTIVES: The management of intractable urinary incontinence in the patient with cloacal or bladder exstrophy/epispadias, failed bladder neck plasty, or failed augmentation cystoplasty remains a surgical challenge. The myofascial wrap, a modification of the rectus fascial wrap, was developed to treat intractable urinary incontinence due to sphincteric incompetence in these problematic cases. A full-thickness, vascularized pedicle of anterior rectus sheath, rectus abdominis muscle, and posterior rector sheath is incorporated into a bladder neck wrap to provide support, mucosal coaptation, and active muscular tone. METHODS: Eight patients (5 females and 3 males) with total urinary incontinence due to sphincteric incompetence underwent the myofascial wrap. Urinary tract pathology included cloacal exstrophy (2), female epispadias (2), classic bladder exstrophy (1), male epispadias (1), myelomeningocele (1), and a pelvic tumor (1). The procedure is performed by harvesting a full-thickness strip of pedicled rectus muscle along with the anterior and posterior fascial sheaths. The strip is passed underneath and then over the bladder neck in a near 360 degrees wrap. The free end of the wrap is anchored into the pubic bone in an ipsilateral subperiosteal pouch. RESULTS: Six of the 8 patients are completely continent, and 2 patients void spontaneously without the need for catheterization. CONCLUSIONS: The myofascial wrap provides support, mucosal coaptation, and muscular tone to an incompetent sphincter and bladder neck. Favorable results in a very difficult population of pediatric patients warrant its continued use.

Captopril (an inhibitor of angiotensin converting enzyme) inhibits obstructive changes in the neonatal rabbit bladder.

OBJECTIVES: To investigate whether angiotensin II has a role in the regulation of bladder smooth muscle growth and function, we developed a model of bladder neck obstruction (BNO) in the neonatal rabbit and investigated the effect of captopril (angiotensin converting enzyme inhibitor) on the obstructive changes in the developing bladder. METHODS: Partial BNO was induced in a group of 2-day-old rabbits (n = 8) by placing a loose 2-0 silk ligature around the vesicourethral junction. A second group of rabbits subjected to the identical partial BNO procedure (n = 8) was given captopril (1 mg/kg/day). Twelve days postobstruction, bladders from these animals, along with paired controls (n = 8), were harvested and assayed for total protein, DNA, and collagen content. RESULTS: Partial BNO resulted in a 170% increase in wet weight (P < 0.05), 132% increase in protein/deoxyribonucleic acid (DNA) ratio (P < 0.05), 75% increase in total DNA (P < 0.05), and 115% increase in total collagen (P < 0.05). When compared with obstructed animals, captopril administration significantly inhibited the increase in total DNA (P < 0.05) and reduced the amount of total collagen (P = 0.054). Examination of histology specimens demonstrated that captopril inhibited the serosal hyperplasia and collagen deposition associated with obstruction. CONCLUSIONS: These data demonstrate that captopril partially inhibits the changes in the neonatal rabbit bladder associated with obstruction, supporting the hypothesis that angiotensin II is involved in the regulation of bladder smooth muscle growth and collagen production.

Release of [Met5]enkephalin from the spinal cord by intraventricularly administered endomorphin-2, but not endomorphin-1 in the anesthetized rat.

Effects of intraventricular injection of endomorphin-1, endomorphin-2 and beta-endorphin on the release of immunoreactive [Met(5)]enkephalin from the spinal cord were studied in pentobarbital anesthetized rats. Intraventricular injection of endomorphin-2, but not endomorphin-1, caused an increased release of immunoreactive [Met(5)]enkephalin in the spinal perfusates. Beta-endorphin given intraventricularly also increased the release of immunoreactive [Met(5)]enkephalin in an amount 15-fold higher than that produced by endomorphin-2. The increase of the release of immunoreactive [Met(5)]enkephalin induced by endomorphin-2 was blocked by mu-opioid receptor antagonist CTOP. Our result suggests that endomorphin-2 stimulates another subtype of mu-opioid receptor different from that acted by endomorphin-1 at the supraspinal site and subsequently increases the release of [Met(5)]enkephalin from the spinal cord.

Evaluation of the feasibility of and results of measuring health-status changes in patients undergoing surgical treatment for skeletal metastases.

The goal of treating patients with skeletal metastases is to decrease pain and improve or maintain physical function. Assessment of the effectiveness of treatment should therefore include evaluation of patient-rated measures of quality of life. The primary objective of the study was to determine the feasibility of studying the effect of surgical treatment of skeletal metastases on quality of life. The secondary objective was to provide data that begin to characterize this effect. The characteristics of patients with skeletal metastases are heterogeneous, patient enrollment in the study may be low, high attrition occurs secondary to death, and well accepted health-status measures (such as the Short Form-36) may be ineffective at detecting changes in health status; therefore, it is difficult to study these patients. High attrition and adjuvant treatment with radiation or chemotherapy made it impractical to draw firm conclusions about the effect of surgical treatment, but a trend toward improvement in selected health-status measures for both physical and mental health was noted. Analysis of patient-rated health-status scores as predictors of survival indicates that improvement in these scores 6 weeks after surgery is associated with an increase in the length of survival following surgery.

Rapid assessment of ventilation by measurement of carbon dioxide elimination during high-frequency ventilation of kittens.

Monitoring of the effectiveness of ventilation is a significant problem during high-frequency ventilation (HFV). The time necessary to achieve equilibrium of the arterial tension of carbon dioxide (Paco2) following step changes in ventilation is appreciable, because of large body stores of CO2. Waiting for Paco2 to reach equilibrium is not only time-consuming but a potentially dangerous means of monitoring ventilator adjustments during HFV. Five kittens of mean +/- SD 1,082 +/- 383 gm weight were studied during HFV, both with normal lungs and lungs injured by saline lavage-induced surfactant depletion. The transcutaneous tension of carbon dioxide (Ptcco2) was monitored continuously to determine the time required to achieve equilibrium of Paco2 following a step change in ventilation. The rate of pulmonary CO2 elimination (VECO2) was measured immediately before and immediately after (less than 12 sec) step changes in ventilation and was used to predict the change in Paco2 achieved once equilibrium was reestablished. With normal lungs, equilibration time following step changes in ventilation was found to be approximately 20 minutes. After step decreases in ventilation of the injured lung, achieving equilibrium state took significantly longer, approximately 30 minutes. The Paco2 predicted was significantly related to the change in Paco2 achieved at equilibrium for both normal and injured lung studies. We concluded that direct monitoring of VECO2 during HFV may be a useful clinical monitoring technique, allowing rapid and accurate assessment of the efficiency of ventilation following step changes in ventilation and potentially assisting in optimizing ventilator settings.