Biomedical subjects
L Brubaker
Publications and source records attributed to L Brubaker.
Effects of pudendal nerve injury in the female rat.
To test a neurogenic hypothesis for external urethral sphincter (EUS) dysfunction associated with urinary incontinence, the proximal pudendal nerve was crushed in anesthetized retired breeder female rats (n = 5) and compared with a sham lesion group (n = 4). Outcome measures included concentric needle electromyograms (EMGs) from the target EUS, voiding patterns during a 2-hour dark period, and micturition data over a 24-hour period. Fast Blue (FB) was introduced to the crush site at the time of injury and Diamidino Yellow (DY) to the EUS at the time the rats were killed (3 months post-operative), when histological analysis of the nerve and urethra was also performed. EMG records indicated the EUS motor units undergo typical denervation changes followed by regeneration and recovery. Voiding patterns from the crush group show a significant increase of small urine marks in the front third of the cage. At 1-2 weeks post-op, the frequency of voids was significantly increased in the crush group compared to pre-op and late post-op time periods. The mean volume voided in the light phase at the early post-op time was significantly increased in the sham group. Light and electron microscopic patterns seen in nerve and muscle suggest the regenerating motor units maintain a structural integrity. Motoneurons in the lower lumbar cord were labeled with either DY (14. 5 +/- 6.8), FB (31.7 +/- 23.7), or both (35.0 +/- 17.5) tracers, indicating approximately 54% of the crushed pudendal neurons regenerated to the EUS. In conclusion, several measures suggest this reversible crush lesion induces mild urinary incontinence. This animal model is promising for further development of hypotheses regarding neural injury, the pathogenesis of incontinence, and strategies aimed at prevention and treatment. Neurourol. Urodynam. 19:53-69, 2000.
Complex repetitive discharges during urethral sphincter EMG: clinical correlates.
Complex repetitive discharges (CRDs) are a form of abnormal needle electromyographic (EMG) activity associated with a variety of neuromuscular disorders, including chronic denervation. Urethral CRDs have also been associated with symptoms of voiding dysfunction. We reviewed the findings of 351 consecutive urethral sphincter EMG studies to characterize the patients with CRDs in our patient population and further to characterize the peri-operative course of any patient with urethral CRDs who underwent surgery for genuine stress incontinence (GSI). Among the 351 women studied, a subgroup of 27 (8%) women demonstrated CRDs during their study. Patients with CRDs were more likely to report the symptom of strain voiding (48% of patients with CRDs, 18% of patients without CRDs; chi(2)((1)) = 17.6, P < 0.001). Patients with CRDs were also more likely to have undergone prior urethral dilation (15% of patients with CRDs versus 2% of patients without CRDs, chi(2)((1)) = 9.5, P < 0.01). Patients with CRDs were similar to patients without CRDs with respect to symptoms of incontinence and history of hysterectomy or surgery for incontinence. Ten patients who had urethral CRDs underwent surgery for their GSI with a 90% success rate. The duration of post-operative catheterization did not differ from that of our general population of patients undergoing similar procedures. Urethral CRDs appear to be a non-specific finding, and it is premature to alter the approach to patients with lower urinary tract dysfunction for this reason.
Ultrastructure of detrusor and urethral smooth muscle in women with urinary incontinence.
OBJECTIVE: We performed a quantitative study to determine whether mixed urinary incontinence was associated with any ultrastructural changes in detrusor and urethral smooth muscle. STUDY DESIGN: Detrusor and urethral smooth muscle biopsy specimens were obtained at the time of laparotomy from 5 women aged 35 to 65 years with mixed urinary incontinence and from a control group of 5 continent women. Smooth muscle morphologic characteristics were assessed from a systematic random sample of electron micrographs. A further 16 urethral biopsy specimens were similarly analyzed to confirm the findings of the initial study. RESULTS: The electron-dense portion of the sarcolemma was smaller in urethral biopsy specimens taken from patients with intrinsic sphincter deficiency than in those from control subjects (chi(2)((1)) = 4.9; P =.027). No other morphologic characteristics were unique to patients with incontinence. CONCLUSIONS: Our study suggests that focal adhesion architecture is decreased in urethral smooth muscle of patients with intrinsic sphincter deficiency.
Electrical stimulation in overactive bladder.
Electrical stimulation is an effective and well-tolerated treatment for overactive bladder. Initial work in animals indicated the potential of this treatment, and early clinical experience in Europe further supported its likely efficacy. Although the mechanism of action of electrical stimulation remains unproven in humans, it is believed to be a neuromodulating therapy which affects the neural signaling that controls continence. There is also strong evidence that electrical stimulation affects striated muscle. The therapy can cause hypertrophy of skeletal muscle fibers, possibly by the recruitment of faster-conducting motor units, which would not normally be recruited during voluntary efforts. In addition, electrical stimulation can alter the expression of myosin isoforms, favoring a conversion to type I muscle. Despite our incomplete understanding of the mechanism of action of electrical stimulation, clinical devices have been developed quickly. Case series have been reported throughout Europe. These were followed by controlled clinical trials in the United States. There is good evidence that the use of vaginal electrical stimulators can reduce the occurrence of symptoms of overactive bladder in about half of the patients treated. Multiple uses of nonimplanted stimulation, including thigh stimulation, anal stimulation, and direct pelvic muscle stimulation, have been reported. In these trials, it is common for objective findings to be poorly correlated with subjective reports of improvements or cure. Patients frequently report that the urge-to-leak time improves, but this is difficult to measure objectively. The use of nonimplanted devices is effective and well tolerated, and should precede the use of implanted devices. A direct comparison with other effective methods of treatment for overactive bladder is warranted.
The antigenicity of fascia lata allografts.
OBJECTIVE: To determine whether commercially available fascia lata allograft material contains donor antigens. MATERIALS AND METHODS: Human leukocyte antigens (HLA) class I and II were assessed in: (i) freeze-dried fascia lata allografts; (ii) a Tutoplast fascia lata graft (Mentor Urology, Santa Barbara, CA, USA); (iii) an acellular dermal graft; and (iv) a successful donor fascia sacrocolpopexy graft one year after implantation, using a polymerase chain reaction sequence-specific primer-based assay. RESULTS: The donor for both the freeze-dried fascia lata and Tutoplast fascia lata was fully HLA-typed. At one year after implantation, antigens from the implanted sacrocolpopexy graft matched the host blood antigens. The antigenicity of the acellular dermal graft could not be ascertained because this material interfered with the assay. CONCLUSION: Donor fascia lata grafts prepared by freeze-drying or by the Tutoplast technique retain donor antigens. The significance of this antigenicity is unknown. All donor antigens are replaced by host antigens after implantation.
The fate of rectus fascia suburethral slings.
OBJECTIVE: Autologous rectus fascia is commonly used to construct suburethral slings for the treatment of genuine stress incontinence. This fascia performs well and has not been associated with clinical problems related to its choice as a sling material. However, the histologic appearance of such slings after implantation has not been documented. STUDY DESIGN: At the time of revision of autologous rectus fascia suburethral slings in 5 patients, biopsy specimens of the slings were obtained and submitted for histologic examination. A specimen of rectus fascia before implantation was also obtained from a sixth patient who had no symptoms. RESULTS: After implantation autologous rectus fascia slings remain viable. There is fibroblast proliferation, neovascularization, and remodeling of the graft. No evidence of inflammatory reaction or of graft degeneration was detected. A linear orientation of connective tissue and fibroblasts was seen in some areas, whereas other areas had remodeled to form tissue similar to noninflammatory scar. CONCLUSION: Autologous rectus fascia slings undergo extensive remodeling after implantation.
Urethral collagen morphologic characteristics among women with genuine stress incontinence.
OBJECTIVE: This was a study of the morphologic characteristics of urethral collagen in women with stress incontinence and continent control women. STUDY DESIGN: Urethral needle biopsy specimens were obtained from 31 women. Fifteen women were continent, and the other 16 had undergone full urogynecologic assessment for symptoms of urinary incontinence. Biopsy specimens were assessed under electron microscopy. Mean collagen fibril diameter was measured and collagen morphologic characteristics were assessed. RESULTS: The biopsy specimens from 30 women were included in the analysis. Collagen fibril diameter did not vary with continence status, the presence of pelvic organ prolapse, age, race or hormonal status. Alterations in collagen fibril morphologic characteristics were evident in the biopsy specimens from nine patients with incontinence. The alterations in collagen morphologic characteristics fell into three patterns, which for convenience were referred to as the obscured pattern, the dense pattern, and the degenerative pattern. CONCLUSION: Altered collagen morphologic characteristics are found in some patients with stress incontinence, and possible causes for those alterations are suggested by their appearances.
The anatomic and functional variability of rectoceles in women.
Fluoroscopic parameters of the rectum in women with pelvic organ prolapse were studied. Ninety-eight consecutive women undergoing reconstructive pelvic surgery completed a urogynecologic history with physical examination and pelvic floor fluoroscopy. The presence of rectocele and contrast trapping was determined on each fluoroscopic study. Each frame of the study was measured to determine the rectal width. Seventy-eight per cent of the women had fluoroscopically demonstrated rectoceles. Their maximum and minimum rectal widths were larger than those of women without rectoceles. Contrast-retaining rectoceles were larger than non-contrast retaining rectoceles. Fluoroscopic evidence of contrast retention did not relate to patient symptoms. There was no difference in the grade of posterior wall prolapse in women with and without rectoceles. Rectoceles have anatomic and functional variability. Fluoroscopy may be a valuable adjunct to the physical examination in assisting gynecologic surgeons to refine their surgical approach for rectocele repair.
Pubic osteomyelitis and granuloma after bone anchor placement.
The use of bone anchors as a superior fixation for suburethral slings is becoming popular. We present a case report of pubic osteomyelitis and granuloma after bone anchor placement. A 71-year-old woman underwent placement of a vaginal wall sling using pubic bone anchors placed through a suprapubic incision. Recurrent swelling of the mons pubis required re-exploration and removal of the anchors from an infected pubic bone. When symptoms persisted over the following 10 months, the patient underwent repeat surgery and excision of a pubic bone granuloma. The use of bone anchors in suburethral sling surgery is associated with possible increase in patient morbidity, and no benefit to the patient has been shown.
A comparison of women with primary and recurrent pelvic prolapse.
OBJECTIVE: Our purpose was to identify clinically relevant differences in women with primary and recurrent pelvic organ prolapse. STUDY DESIGN: Consecutive women undergoing reconstructive surgery completed a urogynecologic history and physical examination and underwent either multichannel urodynamic testing or pelvic floor fluoroscopy, or both. Two groups were compared: primary (no prior surgery for pelvic organ prolapse) and recurrent. RESULTS: One hundred eighty-one consecutive women were studied-103 with primary and 78 with recurrent prolapse. The groups were similar with respect to age, race, weight, vaginal parity, prolapse stage, urodynamic diagnosis, extent of visceral malposition, and common urinary, anorectal, and sexual symptoms. Clinically relevant differences were found, with the recurrent group having shorter vaginal lengths (P =. 0005), being more likely to have had a hysterectomy for a nonprolapse indication (P =.00018) and to be receiving hormone replacement therapy (P =.00003). CONCLUSION: The women with primary and recurrent pelvic organ prolapse in this population were remarkably similar in many quantifiable parameters measured. The clinical differences may be related to previous surgery for pelvic organ prolapse.
Histologic analysis of needle biopsy of urethral sphincter from women with normal and stress incontinence with comparison of electromyographic findings.
OBJECTIVE: Our goal was to compare urethral sphincter biopsy and needle electromyography between women who had genuine stress incontinence and those who did not. STUDY DESIGN: Seventeen continent women and 10 women with stress incontinence had urethral sphincter needle electromyography and urethral biopsy specimens blindly processed for light and electron microscopy. RESULTS: The continent group had greater skeletal muscle content and percentage in each muscle fascicle and each urethral sphincter. The group with genuine stress incontinence had higher connective tissue content. All urethral skeletal muscle was type 1. The smooth muscle was "multiunit" type and was morphologically indistinguishable between the 2 groups. On electromyography, patients with genuine stress incontinence had significantly more fibrillation potentials, fewer motor unit action potentials, a higher percentage of polyphasia, and less maximum voluntary electrical activity than control subjects. CONCLUSIONS: Women with stress incontinence differ from continent women in skeletal muscle volume, amount of fibrosis, and electromyographic parameters; these differences support a neurogenic contribution to genuine stress incontinence. Urethral sphincter has only type 1 skeletal muscle and "multiunit" type smooth muscle.
Functional failure of fascia lata allografts.
OBJECTIVES: Fascia lata allografts are commonly used in urogynecologic procedures. Functional failure of several grafts has occurred, and such failure has been recognized as a materials problem in 12 patients. STUDY DESIGN: Twelve patients with failure of an initial urogynecologic procedure performed with irradiated and freeze-dried donor fascia lata grafts underwent reoperation. Portions of the implanted fascia lata grafts could be retrieved in 7 cases. Graft specimens underwent histologic processing followed by hematoxylin and eosin staining. RESULTS: Histopathologic analyses of the retrieved material demonstrated several ongoing processes in the failed grafts. A few grafts showed areas of ideal remodeling. Most grafts, however, showed areas of disorganized remodeling and areas of graft degeneration. Evidence of immune reaction to the graft was observed in some cases. CONCLUSION: The high materials failure rate associated with the use of irradiated and freeze-dried donor fascia lata grafts suggests that such tissue should not be used for urogynecologic procedures.
Outcome after rectovaginal fascia reattachment for rectocele repair.
OBJECTIVE: This study was undertaken to determine the effects of rectovaginal fascia reattachment on symptoms and vaginal topography. STUDY DESIGN: Standardized preoperative and postoperative assessments of vaginal topography (the Pelvic Organ Prolapse staging system of the International Continence Society, American Urogynecologic Society, and Society of Gynecologic Surgeons) and 5 symptoms commonly attributed to rectocele were used to evaluate 66 women who underwent rectovaginal fascia reattachment for rectocele repair. All patients had abnormal fluoroscopic results with objective rectocele formation. RESULTS: Seventy percent (n = 46) of the women were objectively assessed at 1 year. Preoperative symptoms included the following: protrusion, 85% (n = 39); difficult defecation, 52% (n = 24); constipation, 46% (n = 21); dyspareunia, 26% (n = 12); and manual evacuation, 24% (n = 11). Posterior vaginal topography was considered abnormal in all patients with a mean Ap point (a point located in the midline of the posterior vaginal wall 3 cm proximal to the hymen) value of -0.5 cm (range, -2 to 3 cm). Postoperative symptom resolution was as follows: protrusion, 90% (35/39; P <.0005); difficult defecation, 54% (14/24; P <.0005); constipation, 43% (9/21; P =.02); dyspareunia, 92% (11/12; P =.01); and manual evacuation, 36% (4/11; P =.125). Vaginal topography at 1 year was improved, with a mean Ap point value of -2 cm (range, -3 to 2 cm). CONCLUSION: This technique of rectocele repair improves vaginal topography and alleviates 3 symptoms commonly attributed to rectoceles. It is relatively ineffective for relief of manual evacuation, and constipation is variably decreased.
The external urethral barrier for stress incontinence: a multicenter trial of safety and efficacy. Miniguard Investigators Group.
OBJECTIVE: To assess the efficacy and safety of an external urethral barrier for the management of mild to moderate stress urinary incontinence in adult women. METHODS: Four hundred eleven women with the symptom of stress urinary incontinence in 12 United States centers participated. Additional inclusion and exclusion criteria were applied before protocol device use, and ultimately 390 subjects began device use. Outcome measures for efficacy and safety were assessed. Efficacy was evaluated by the number of leakage episodes using a voiding diary, subjective urinary leakage severity, incontinence impact scores, and pad testing. Safety was evaluated by symptom assessment, urinalysis, urine culture, measurement of postvoid residual urine volume, vulvar cytology, vaginal culture, and (n = 81) cystometric testing. RESULTS: Efficacy was indicated by statistically significant reductions in the number of leakage episodes, subjective leakage severity scores, incontinence impact scores, and pad-test loss during device use. The data also indicated that the device was safe, as evidenced by the lack of statistically significant changes in the percentage of subjects with urinary tract infections during device use or in postvoid residual urine volume and cystometric indices. Symptoms of vulvar irritation or lower urinary tract discomfort occurred in a small percentage of subjects but were generally transient, and only three women discontinued using the device. CONCLUSION: The external urethral barrier appears to be a safe nonsurgical alternative to absorbent products for the management of mild to moderate stress urinary incontinence in adult women.
Failure of allograft suburethral slings.
OBJECTIVES: To report our experience of using freeze-dried irradiated fascia lata allografts for suburethral sling procedures. PATIENTS AND METHODS: Between December 1996 and September 1998, 35 patients (mean age 60.25 years, range 37-79) underwent suburethral sling placement with fascia allograft. These patients were reviewed, with the findings at the time of any surgical re-exploration. Eleven (31%) had undergone prior surgery for genuine stress incontinence and 32 (91%) had a preoperative diagnosis of intrinsic sphincter deficiency. RESULTS: On re-operation for persistent or recurrent stress incontinence, the allograft was present but grossly degenerated in two (6%) patients and completely absent in five (14%) patients. Histology of a retrieved graft fragment showed both fibroblast proliferation and degeneration within the graft. CONCLUSION: The use of freeze-dried, irradiated fascia lata for suburethral sling procedures was associated with a material failure rate of >/=20%. We caution against its use in this setting.
Pudendal denervation affects the structure and function of the striated, urethral sphincter in female rats.
Our aim was to examine the effects of denervation on urethral anatomy and urine voiding pattern. Rats usually void at one end of their cage, which gives a behavioral index of continence. The voiding preference for denervated rats was decreased to 88.8 + 4.7%, n = 32, P < 0.001, compared to improvements with time for unoperated (117 +/- 10%, n = 16) or sham-operated rats (105 +/- 8%, n = 5). The volume of urine or the frequency of voidings between denervated, unoperated or sham-operated rats did not differ significantly. Urethral sections were analyzed immunochemically and quantified morphometrically. Smooth muscle volume remained constant but skeletal muscle volume decreased after denervation, from 43 +/- 2% to 36 +/- 3% (P < 0.05, n = 5). Fiber diameter decreased from 14.3 +/- 1.4 microm to 8.5 +/- 0.7 microm (P < 0.005). We concluded that pudendal nerve transection in female rats causes behavioral alterations in voiding and muscular atrophy of the striated sphincter.
Vaginal delivery and the pelvic floor.
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