Biomedical subjects

Margot S Damaser

Publications and source records attributed to Margot S Damaser.

12 recordsLinked to original sources

PubMed2006

Effect of estrogen on urethral function and nerve regeneration following pudendal nerve crush in the female rat.

PURPOSE: We tested the hypothesis that estrogen promotes improvement in urethral function and nerve regeneration following bilateral pudendal nerve crush in ovariectomized female rats. MATERIALS AND METHODS: A total of 52 female rats underwent ovariectomy 6 days before bilateral pudendal nerve crush. Estrogen and sham capsules were subcutaneously implanted at the time of nerve crush in 16 and 14 of these rats, respectively, while 22 served as unoperated controls. Seven days following nerve crush urethral LPP testing was performed using urethane anesthesia. Spinal cord sections containing motoneurons of Onufrowicz's nucleus were subjected to in situ hybridization to detect the expression of beta(II) tubulin mRNA, a marker of the neuroregenerative response. RESULTS: Mean LPP +/- SEM was significantly decreased after pudendal nerve crush in sham treated animals compared to unoperated controls (32.1 +/- 6.8 vs 54.4 +/- 11.6 cm H2O). Rats with an estrogen implant had an LPP of 42.5 +/- 16.8 cm H2O, which was significantly greater than rats given sham implants and significantly less than unoperated controls. Rats that received an estrogen implant had increased beta(II) tubulin mRNA expression compared to those that received a sham implant. CONCLUSIONS: The results of this research suggest that estrogen given at the time of pudendal nerve crush promotes and facilitates the recovery of urethral function and an increase in the nerve regenerative response. Future studies will include the investigation of molecular pathways activated by estrogen in response to peripheral nerve injury.

Animals↗

PubMed2005

Biocompatibility of nitinol and stainless steel in the bladder: an experimental study.

PURPOSE: We tested the biocompatibility of nitinol, a nickel titanium alloy, and stainless steel (SS) as bladder implant materials. MATERIALS AND METHODS: Rats received a nitinol implant, an SS implant or were sham controls. Two, 3, 6 and 8 weeks following implantation 24-hour voiding behavior studies were performed to investigate bladder irritation. All animals were sacrificed 8 weeks after implantation and a sample of urine was aspirated for culture. The bladders were examined by light microscopy and scanning electron microscopy (SEM). RESULTS: No visible encrustations or infections were noted in urine. Voiding frequency in the light period 6 weeks after implantation was significantly decreased in the 2 implant groups compared with sham controls. There were no other significant differences in frequency or mean volume per void in the light or dark periods at any time point. Light microscopy demonstrated similar implant tissue effects in all groups with little or no inflammation or fibrosis. Under SEM all implants showed a brittle, amorphous coating devoid of cells. The transition between the urothelium mucosa and the rod was smoother for SS than for nitinol, suggesting an affinity of SS for mucosa. In all nitinol rods discontinuity was present between the mucosa and rod. CONCLUSIONS: Nitinol and SS do not cause more irritation than the effects of surgery alone and the 2 materials seem to be biocompatible in the bladder. Nitinol may be more inert than SS based on SEM results.

Alloys↗

PubMed2004

Short-term functional and neuroregenerative response of the urethra to ovariectomy and vaginal distension in female rats.

The objective of this study was to investigate the effects of ovariectomy (OVX) and vaginal distension (VD) on leak point pressure (LPP) and pudendal nerve regenerative response in the female rat. Twenty rats underwent OVX 3 days prior to either VD or sham distension. Seventeen rats did not receive OVX but underwent either VD or sham distension. Four days after distension, LPP testing was performed. In situ hybridization for beta(II) tubulin mRNA, an indicator of the neuroregenerative response, was performed on motoneurons of the pudendal nerve. In the non-OVX group, LPP was significantly decreased after VD. After OVX, the difference in LPP between VD and sham rats did not quite reach the level of statistical significance. There was a statistically significant interaction between the effects of OVX and VD on LPP. There was no significant difference in in situ hybridization results between any of the groups. No neuroregenerative response of motoneurons of the pudendal nerve was observed after either VD or OVX.

Animals↗

PubMed2004

Basic science and translational research in female pelvic floor disorders: proceedings of an NIH-sponsored meeting.

AIMS: To report the findings of a multidisciplinary group of scientists focusing on issues in basic science and translational research related to female pelvic floor disorders, and to produce recommendations for a research agenda for investigators studying female pelvic floor disorders. METHODS: A National Institutes of Health (NIH)-sponsored meeting was held on November 14-15, 2002, bringing together scientists in diverse fields including obstetrics, gynecology, urogynecology, urology, gastroenterology, biomechanical engineering, neuroscience, endocrinology, and molecular biology. Recent and ongoing studies were presented and discussed, key gaps in knowledge were identified, and recommendations were made for research that would have the highest impact in making advances in the field of female pelvic floor disorders. RESULTS: The meeting included presentations and discussion on the use of animal models to better understand physiology and pathophysiology; neuromuscular injury (such as at childbirth) as a possible pathogenetic factor and mechanisms for recovery of function after injury; the use of biomechanical concepts and imaging to better understand the relationship between structure and function; and molecular and biochemical mechanisms that may underlie the development of female pelvic floor disorders. CONCLUSIONS: While the findings of current research will help elucidate the pathophysiologic pathways leading to the development of female pelvic floor disorders, much more research is needed for full understanding that will result in better care for patients through specific rather than empiric therapy, and lead to the potential for prevention on primary and secondary levels.

Animals↗

PubMed2004

Three dimensional virtual reality model of the normal female pelvic floor.

The anatomy of the pelvic floor is complex and difficult to visualize from conventional two-dimensional anatomy pictures. The goal of this project was to establish the methods necessary to develop a static three-dimensional virtual reality model of the normal female pelvic floor from high-resolution magnetic resonance imaging (MRI) scans. An asymptomatic nulliparous 23-year-old female with no urinary incontinence symptoms underwent a high-resolution pelvic floor MRI scan. Selected pelvic floor structures were manually segmented: bladder, urethra, vagina, uterus, cervix, levator ani, obturator externus, obturator internus, and pubic bone. With high-resolution scans, accurate segmentation of the structures was possible. The completed models were displayed on an ImmersaDesk Virtual Reality system and three clinicians verified their accuracy. Stereovision glasses were used to enhance the model while a receiver tracked head position. Three-dimensional virtual reality models of the female pelvic floor can enhance our understanding of anatomy and physiology of this complex part of the body. They can be used as tools for both research and teaching, facilitating improved treatment of pelvic floor pathologies.

Adult↗

PubMed2003

Bladder pressure monitoring during intermittent catheterization: a comparison of gauges and methods.

AIMS: We previously have investigated a technique for serial bladder pressure measurements in patients with spinal cord injury (SCI) using intermittent catheterization. In the current study, we compared an FDA-approved digital gauge with the previously studied analog gauge and studied the effects of hydrostatic pressure differences. METHODS: Either a digital or an analog pressure gauge was attached to each subject's catheter just before bladder catheterization. Both immediate and stable pressures were recorded. The bladder was then drained until nearly empty and pressure was again recorded (almost empty bladder pressure). Detrusor pressure was estimated as full minus almost empty bladder pressure. Bladder pressures greater than 40 cm H2O were presumed to represent bladder contractions. To investigate the effects of hydrostatic pressure, additional measurements, adjusting the level of the air-urine meniscus, were obtained in three subjects. RESULTS: Recordings were made from nine SCI subjects using both gauges. Estimates of detrusor pressure, with and without bladder contractions, and associated bladder volumes, were not significantly different between digital and analog gauges. In the absence of bladder contractions, detrusor pressure with the meniscus at the end of the catheter (5 +/- 1 cm H2O) was significantly lower than that recorded with no adjustment of the urine meniscus (12 +/- 1 cm H2O). CONCLUSIONS: Standardizing measurement techniques to equalize hydrostatic pressures should facilitate reliable estimates of detrusor pressure. Frequent monitoring of bladder pressure using this technique may assist with the urological care of SCI patients.

Adult↗

PubMed2003

Predicting urethral area from video-urodynamics in women with voiding dysfunction.

AIMS: Mathematical models are useful for developing predictive parameters for characterizing the biomechanics of voiding dysfunction. The goal of this project was to test a one-dimensional steady flow model used to predict the minimum cross-sectional urethral area from urodynamic data. METHODS: Nine adult female subjects underwent video-urodynamic testing. By using Bernoulli's formula and the Torricelli theorem, the minimum urethral area was predicted from pressure and flow rate at the moment of maximum flow rate during voiding. This prediction was compared with the minimum cross-sectional area of the urethra, which was calculated from minimum urethral diameter as measured from fluoroscopy, assuming a circular cross-section. RESULTS: The maximum flow rate during voiding was 14.4 +/- 3.0 mL/sec. Mean bladder, abdominal, and detrusor pressures simultaneous with maximum flow rate were 63 +/- 7, 29 +/- 6, and 33 +/- 6 cm H(2)O, respectively. Mean minimum cross-sectional area of the urethra from fluoroscopy was 8.0 +/- 2.0 mm(2). Mean minimum cross-sectional area of the urethra predicted by the mathematical model was 5.0 +/- 1.0 mm(2) using bladder pressure and 7.0 +/- 2.0 mm(2) using detrusor pressure. There were no significant differences between the three cross-sectional area measures. However, when area predictions were expressed as percentage of fluoroscopic measurements, the estimate from detrusor pressure (97 +/- 13%) was significantly larger than the estimate from bladder pressure (69 +/- 7%). CONCLUSIONS: A steady flow model is accurate enough on average to describe urine flow in the urethra. However, it may not be sufficiently accurate to aid in diagnosis of individuals.

Female↗

PubMed2003

Methods of testing urethral resistance in the female rat.

Development of an animal model of stress urinary incontinence is dependent on a measure of urethral resistance, such as leak point pressure (LPP). However, animals will not cough or perform Valsalva maneuvers upon request. The aim of this study was to use urodynamics to compare bladder pressures during spontaneous voids (SV), anesthetized LPP measurement, and induced sneezing in female rats. A suprapubic catheter was implanted in the bladder dome of 10 female rats. Two days later, the rats were tested urodynamically under urethane anesthesia. The bladder was emptied and filled with saline. The abdomen was then depressed manually to increase abdominal pressure while bladder pressure was measured. The bladder pressure when leakage occurred was taken as LPP. In addition, the rats were stimulated to sneeze by cutting off a whisker and using it to tickle the nostril. Both peak pressure and increase in pressure during LPP (43.4 +/- 3.6 and 33.1 +/- 3.8 cm H2O, respectively) were significantly higher than pressures during both SV (30.4 +/- 3.8 and 19.3 +/- 3.4 cm H2O, respectively) and sneeze (9.5 +/- 0.7 and 2.6 +/- 0.5 cm H2O, respectively). The time course of a sneeze (0.6 +/- 0.2 sec) was significantly shorter than the time course of both LPP (4.4 +/- 0.5 sec) and SV (6.9 +/- 1.3 sec). No rat leaked from a sneeze unless the sneeze triggered an SV. LPP triggered a SV in 5 rats and sneeze triggered a SV in 6 rats. With urodynamic measurement, it is possible to easily distinguish between LPPs, SVs, and sneezes. LPP can provide a quantifiable measure of decreased urethral resistance, whereas induced sneezes can provide a diagnostic test for severe incontinence.

Animals↗

PubMed2003

Functional and neuroanatomical effects of vaginal distention and pudendal nerve crush in the female rat.

PURPOSE: We tested the hypothesis that neuroanatomical degeneration near the external urethral sphincter (EUS) would parallel urinary dysfunction after vaginal distention or bilateral pudendal nerve crush in female rats. MATERIALS AND METHODS: A total of 28 female rats underwent bilateral pudendal nerve crush or vaginal distention, or were unoperated controls. Two days later a catheter was implanted into the bladder dome and 2 days after that (4 days after injury) urethral leak point pressure testing was performed with the rat under urethane anesthesia. The pudendal nerve and urethra were then dissected and prepared for light and electron microscopy. RESULTS: Leak point pressure was significantly decreased 4 days after pudendal nerve crush and vaginal distention (29.3 +/- 3.4 and 31.0 +/- 2.5 cm H(2)O, respectively) compared with controls (44.3 +/- 3.4 cm H(2)O). The percentage of nerve fascicles with degeneration near the EUS was significantly greater in the nerve crush (13.1% +/- 1.7%) and vaginal distention (7.2% +/- 2.2%) groups than in the control group (0% +/- 0%). There were fewer nerve fascicles near the EUS in the ventral half of the urethral cross section than in the dorsal half in all 3 groups and the percent of fascicles with degeneration was greater in the ventral half than in the dorsal half in the 2 injury groups. CONCLUSIONS: These results suggest that the pudendal nerve is particularly vulnerable to injury during vaginal distention in this animal model. The 2 injury models may be useful for investigating the pathophysiology of stress urinary incontinence.

Animals↗

PubMed2002

Displacement sequence and elastic properties of anterior prostate/urethral interface during micturition of spinal cord injured men.

The management of complex micturition problems frequently encountered in patients with spinal cord injury (SCI) may be facilitated by characterization of the elastic properties of the prostate. To this end, we have developed a method of evaluating changes in prostate biomechanics using ultrasound (US) images obtained during routine diagnostic urodynamic evaluations. Ultrasound video sequences of the prostate and urethra during voiding were digitized simultaneously with bladder pressure measurement on 76 patients with spinal cord injury, having a mean age of 47 +/- 16 years. Computer enhancement of the bladder/prostate/urethral interface from sequences of 2-D US images facilitated measurement of midprostatic urethral displacement during micturition. Of 76 patients, 21 were able to initiate voiding. Maximum urethral diameter was 12.0 +/- 1.3 mm, with corresponding maximum voiding pressure of 61.6 +/- 1.9 cmH(2)O. Urethral/prostatic pressure strain elastic modulus (Ep) was 960 +/- 624 N/m(2) and stiffness (beta) calculated as the inverse of compliance was 2.8 +/- 0.1. The diameter of the urethra at P(det50+), during the opening phase, was 0.4 +/- 0.1 mm and, during the closing phase, was 0.7 +/- 0.1 mm. During voiding, the anterior prostate was displaced to a greater extent than the posterior prostate. These observations suggest that distension of the prostate/urethra during micturition is hysteretic and nonuniform and indicates regional differences in compliance within the prostate/urethra interface. These regional differences lend support to the concept that the posterior prostate is implicated in the active process of micturition involving the fibromuscular stroma. Clinical application of this method could include quantification of the biomechanics of micturition consequent to spinal injury, prostatic enlargement, and the impact of targeted evaluation of pharmacological interventions.

Adult↗

PubMedDate not supplied

Preliminary study of a genetically engineered spinal cord implant on urinary bladder after experimental spinal cord injury in rats.

The objective of this study was to determine the effect of neurotrophin-secreting Schwann cell implants on the urinary bladder after spinal cord contusion. One hour after severe spinal cord contusion at the T8 to T11 level, carbon filaments containing nonsecreting Schwann cells, brain-derived neurotrophic factor (BDNF)-secreting Schwann cells, neurotrophin-3 (NT-3)-secreting Schwann cells, or Schwann cells secreting both BDNF and NT-3 were implanted into the spinal cord. Untreated spinal cord injured (SCI) rats and noncontused rats (C) were also studied. Two months after spinal cord injury, cystometry was performed and the bladders were studied using light microscopy. SCI rats had significantly increased bladder mass, thickness, and smooth muscle mass compared to C rats. Bladder capacity of SCI rats and rats with spinal cord implants were both significantly greater than that of C rats. This preliminary study suggests that neurotrophin-secreting Schwann cell implants may lead to improved bladder structure after spinal cord injury.

Animals↗

PubMedDate not supplied

Short-term timecourse of bilateral pudendal nerve injury on leak-point pressure in female rats.

The pudendal nerve innervates the external urethral sphincter and, when injured, can contribute to incontinence development. This experiment was designed to study the time course of functional changes in the urethra after pudendal nerve crush in rats. Leak-point pressure (LPP) was measured 2, 4, 7, or 14 days after bilateral pudendal nerve crush and was compared to that of a control group. LPP at all four time points after nerve injury was significantly decreased compared to control values. A minimum was reached 4 days after injury, and LPP appeared to trend upward with increasing time after injury, suggesting that nerve function may begin to recover or compensatory changes in the urethra may occur. Pudendal nerve crush induces decreased LPP in female rats, mimicking the clinical symptoms of stress incontinence. When fully characterized, this model could be useful for preclinical testing of treatment and rehabilitation protocols.

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