Biomedical subjects
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Fecal incontinence is the involuntary loss of gas, liquid, and/or solid stool. It affects 2.2% of the general population. Because fecal incontinence can be socially and psychologically devastating, and is not easily discussed, this figure is probably understated. Patients presenting with fecal incontinence need to be properly assessed, including physiological testing of the pelvic floor muscles and nerves. Identifying any abnormal anatomy or physiology in the pelvic floor helps the clinician develop a care plan that best suits the patient's etiology. Knowledge of the physiology of the pelvic floor musculature and its effects on continence is improving. Treatment options also have broadened. This article describes the current techniques of assessment and treatment, including the "gold standard," and newer investigational procedures offered to patients with complex fecal incontinence.
PURPOSE: Anal sphincter injury is a serious complication of childbirth, which may result in persistent anal incontinence. Occult injuries, visualized with endoanal ultrasonography, have previously been reported in up to 35 percent of females in a British study. The aim of the present study was to study anal sphincter morphology and function before and after delivery in primiparous females in the United States. METHODS: Thirty-eight primiparous patients (mean age, 31 years) were evaluated with endoanal ultrasonography, anal manometry, and pudendal nerve terminal motor latency during pregnancy and after delivery. Bowel function before and after delivery was recorded according to set questionnaires. Cesarean section was performed in three patients. RESULTS: Clinical sphincter tears, requiring primary repair, occurred in 15 percent of the patients. After delivery endoanal ultrasonography revealed disruptions in the external anal sphincter in six patients, but no patient had disruption in the internal anal sphincter. One patient had slight scarring in the external sphincter. Of the seven patients with pathologic findings at endoanal ultrasonography, the left pudendal latency increased after delivery (P < 0.05), and manometric results were reduced. Three of these seven patients had a third-degree or fourth-degree tear during delivery. All investigations were normal in the three patients who underwent cesarean section. CONCLUSIONS: The present study demonstrates a significant frequency of sphincter injuries (20 percent) after vaginal delivery. Obstetricians should be aware of this risk and explicitly inquire about incontinence symptoms at follow-up after delivery.
INTRODUCTION: Anal incontinence is eight times more frequent in females than in males because of injuries sustained at childbirth. The aim of the present study was to determine the long-term costs associated with anal incontinence related to obstetric injuries. METHODS: Sixty-three patients with anal incontinence caused by obstetric sphincter injuries answered questionnaires regarding previous treatments, symptoms, and use of protective products. Of the patients, 31 were treated surgically, 11 with biofeedback, 6 with a combination of surgery and biofeedback, and 15 conservatively. Treatments and their respective costs were obtained from patient records, patient questionnaires, billing database, and Health Care Financing Administration's 1996 inpatient database. Costs were expressed in 1996 dollars. RESULTS: The mean incontinence score changed from 26 at evaluation to 16 at follow-up (P < 0.001). The average cost per patient was $17,166. Evaluation and follow-up charges totaled $65,412, and physiologic assessment accounted for 64 percent of these costs. Treatment charges totaled $559,341, and physician charges accounted for 18 percent of these charges. CONCLUSIONS: Fecal incontinence after childbirth results in substantial economic costs, and treatment is not always successful. New treatment modalities, such as artificial bowel sphincter or dynamic graciloplasty, should be assessed to determine their cost-effectiveness.
PURPOSE: Treatment of severe constipation caused by combined colonic inertia and nonrelaxing pelvic floor is controversial. This study is designed to evaluate the outcome of preoperative biofeedback and subtotal colectomy for patients with combined colonic inertia and nonrelaxing pelvic floor. METHODS: One hundred six patients who underwent subtotal colectomy for intractable constipation from 1982 through 1995 answered a detailed questionnaire regarding postoperative bowel function, symptoms of abdominal pain and bloating, and degree of satisfaction after the operation. Sixteen of these patients had a combination of colonic inertia and nonrelaxing pelvic floor diagnosed by transit marker study, electromyography, and defecography. These patients completed preoperative biofeedback training. RESULTS: Electromyographic relaxation of pelvic floor musculature was demonstrated after the biofeedback treatment in all patients, but symptoms of difficult evacuation persisted. Postoperatively, seven patients (43 percent) had complete resolution of symptoms of constipation or difficult evacuation. Six patients still complained of incomplete evacuation that was severe in two and unresponsive to postoperative biofeedback. Three patients (18 percent) complained of diarrhea (>5 bowel movements per day) and incontinence of liquid stools (at least one episode a week). Nine patients (56 percent) were satisfied despite persistent symptoms. CONCLUSIONS: Subtotal colectomy can improve some symptoms in patients with slow transit constipation and nonrelaxing pelvic floor. However, incomplete evacuation persists in a significant number of patients and almost one-half of patients are dissatisfied with their surgery.
UNLABELLED: The primary treatment for obstetric sphincter injury is overlapping sphincteroplasty. However, despite restoration of the anatomy, only 65 percent of patients are fully continent. PURPOSE: This study was undertaken to determine if postoperative biofeedback improved continence in patients with poor functional outcomes after sphincteroplasty. METHOD: Outcomes of 28 patients who underwent electromyographic biofeedback training after sphincteroplasty for obstetric sphincter injury were reviewed. Nine patients had an accompanying levatorplasty. Average age was 34 (range, 23-57) years. Patients began biofeedback a mean of 32 (range, 2-192) months postoperatively. Before beginning biofeedback, patients completed an incontinence questionnaire, bowel diary, and scored their incontinence. At the end of treatment, they were again asked to score their incontinence and rate their improvement. Using an incontinence scale with a maximum score of 30, the average incontinence score before biofeedback was 20 (range, 13-30). Incontinent episodes per week ranged from one to nine. Sixteen patients were incontinent to solid stool. RESULTS: Overall, the average posttreatment incontinence score decreased from 20 to 3 (P < 0.0001). Average number of incontinent episodes per week decreased from 5.4 to 1.4 (P < 0.0001) Twenty-five patients (89 percent) reported improvement in their continence. All had a posttreatment incontinent score of less than three. Three patients noted no improvement. Of those, one subsequently had a colostomy, one is waiting the implant of an artificial anal sphincter, and one has sought no further treatment. There were no complications reported. CONCLUSION: Biofeedback improves functional outcome after sphincteroplasty and is a reasonable option for patients with less than optimum outcome after sphincteroplasty.
Fecal incontinence, the involuntary passage of gas, liquid, or solid stool, is an underreported problem in our society. The evaluation of fecal incontinence includes a focused history, physical examination, and assessment of the pelvic floor musculature. This article describes the assessment of fecal incontinence, focusing on specific diagnostic tests designed to identify dysfunction of the anal sphincter and adjacent pelvic floor musculature and on the use of these tests in determining an appropriate treatment plan.
PURPOSE: This study was undertaken to evaluate the use of a fully implanted artificial anal sphincter for management of severe fecal incontinence. METHODS: An artificial anal sphincter was implanted in 12 patients who failed conventional management for severe fecal incontinence. Careful patient follow-up was recorded during a mean 58-month follow-up. Patients underwent preoperative and postoperative manometric assessment. Functional and patient satisfaction evaluations were obtained by mailed questionnaire. RESULTS: Three infections and three mechanical complications occurred in four patients (33 percent). A successful outcome was achieved in nine patients (75 percent). Postoperative manometric studies documented establishment of an elevated high-pressure zone compared with preoperative resting pressures. Seven patients returned a detailed functional assessment and patient satisfaction questionnaire at a mean of 40 months postsphincter activation. All seven patients reported continence to solid stool. Two patients had some problems with control of liquid stool, and three had occasional incontinence to flatus. Six of the seven patients rated their bowel control as good to excellent. All seven respondents were satisfied with their functional improvement. CONCLUSIONS: Early experience with an artificial anal sphincter has demonstrated that continence can be restored with acceptable morbidity in patients with severe fecal incontinence.
Normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) received aminopeptidase M (AmM) delivered into the paraventricular nucleus of the hypothalamus (PVN). Resulting changes in blood pressure were recorded in both anesthetized and alert animals. The findings indicate significant dose-determined decreases in blood pressure in members of both strains with SHR more responsive than WKY rats. The respective drops in blood pressure for members within each strain were equivalent for the anesthetized and alert conditions. Pretreatment with the specific angiotensin receptor antagonist, sarthran, [Sar1, Thr2] Angll, into the PVN greatly diminished these responses, suggesting the involvement of the brain angiotensin system. Additionally, a sympathetic nervous system blocker, hexamethonium, and the arginine vasopressin antagonist, Pmp1, O-Me-Tyr2-[Arg] vasopressin, were peripherally administered to assess the potential contributions of these systems to cardiovascular regulation by the brain angiotensin system. The use of these blockers, individually and combined, attenuated responsiveness to infusion of AmM into the PVN. We conclude that AmM can act as a hypotensive agent in both SHR and WKY rats, and that this decrease in blood pressure is at least partially mediated via the brain angiotensin system although other systems may play a role.
The brain angiotensin (ANG II and III) system is known to play an important role in the central control of cardiovascular function and body water homeostasis. A number of components of the angiotensin system including active peptides, precursors, synthetic enzymes, and receptors have been localized to specific brain nuclei including the paraventricular nucleus (PVN) of the hypothalamus. We and others have hypothesized that the PVN is a major integrative hub of the central angiotensin system receiving angiotensinergic input from central detectors (circumventricular organs) and sending efferents to higher brain and spinal cord centers. Implicit in this idea is that angiotensins, like all neurotransmitters, should be releasable with appropriate chemical and physiological stimuli. Therefore we examined the ability of water deprivation or direct infusion of either 65 mM K+ or 80 microM veratridine to stimulate the release of angiotensins from the PVN of the rat. Using push-pull cannulas to perfuse the PVN and radioimmunoassay (RIA) to analyze the superfusate for immunoreactive angiotensins, we established that 24 h of water deprivation resulted in an approximate 5-fold increase in the angiotensin release rate, whereas 48-h deprivation produced a dramatic 492-fold increase in release. Direct infusion of 65 mM K+ into the PVN was unable to stimulate angiotensin release, but 80 microM veratridine elicited a sevenfold increase in the angiotensin release rate. High-performance liquid chromatographic separation and RIA analysis of veratridine- and water deprivation-stimulated angiotensin release demonstrated that 93.4% of the releasable angiotensin coeluted with ANG III, whereas only 6.8% eluted with authentic ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)
The present investigation examined the abilities of angiotensin (ANG) II and III to produce increases in blood pressure and drinking when microinfused into the paraventricular nucleus (PVN) of the hypothalamus of the Sprague-Dawley rat. Dose-dependent elevations in systemic blood pressure and heart rate were measured to both ANG II and III in the anesthetized rat, with ANG II more potent than ANG III at the two highest doses examined. Pretreatment with the specific ANG receptor antagonist [Sar1,Thr8]ANG II (sarthran), blocked subsequent ANG II- and III-induced elevations in blood pressure, suggesting that these responses were dependent on the activation of ANG receptors. A similar analysis in awake rats yielded nearly equivalent results. A final experiment demonstrated that microinfusions of ANG II and III into the PVN produced drinking in a dose-dependent manner, with greater consumption to ANG II than ANG III. Again, sarthran was found to block the dipsogenic response. Histological examination revealed that the location of the injection site was linked to the character of the ANG-dependent response. These data suggest that the PVN may play a critical role in mediating central ANG effects on body water homeostasis and blood pressure regulation. Furthermore, it appears that subnuclei of the PVN may participate differentially in ANG-mediated actions.
Rats received the aminopeptidase inhibitors amastatin (AM) and bestatin (BE), and carboxypeptidase inhibitor Plummer's (PL) via intracerebroventricular infusion in various combinations, i.e. PL alone, AM + BE, and a cocktail consisting of AM + BE + PL. Blood pressure responses were recorded and a postinfusion sample of cerebrospinal fluid (CSF) was radioimmunoassayed for endogenous angiotensin levels. Results indicate that CSF angiotensin was increased approximately 1.5x over control levels when PL was infused; a 2.5x increase accompanied AM + BE administration; and a 10.3x elevation was measured when all 3 inhibitors were infused as a cocktail. Concomitant elevations in blood pressure accompanied increased concentrations of angiotensin. We conclude that endogenous levels of angiotensin can be significantly increased in the ventricular space when a combination of these inhibitors is utilized to protect both the amino and carboxyl terminals of the angiotensin molecule from enzymatic degradation.
Anorectal manometry is becoming a commonly applied investigation in the field of colon and rectal surgery. Until now, however, most of this testing was performed in specialized units, which involved considerable expense and expertise to run. The authors assessed a commercially available mini-transducer and an air-filled microballoon catheter for their applicability to clinical anorectal manometry. This system is very accurate and is proving very useful in the ambulatory setting, on hospital wards, and in the operating room. It provides a simple alternative for areas where more sophisticated manometric systems are not available.
The preoperative staging of rectal cancer has important implications for treatment as local therapies become increasingly utilized. Seventy-seven patients underwent preoperative staging using endorectal ultrasonography. All patients had complete pathologic staging and none had preoperative radiotherapy. Depth of invasion of the tumor was accurately predicted in 75 percent of cases in the entire group, with 22 percent overstaged and 3 percent understaged. Accuracy improved greatly over the study period, and in the past six months, 95 percent have been accurately staged for depth of invasion with 5 percent overstaged. Lymph nodes have been properly classified into positive and negative groups in 88 percent of cases in the past year, with a specificity of 90 percent and a sensitivity of 88 percent. Endorectal ultrasound is an accurate preoperative staging modality. Accuracy is improved greatly with increased experience and it has been found that the 5-layer anatomical model facilitates accurate staging. Introduction of the ultrasound probe through a previously placed proctoscope ensures complete scanning of the entire lesion and should be used for the majority of examinations.
Two aminopeptidase inhibitors, amastatin (AM) and bestatin (BE), were employed in 3 strains of rats, spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD), to investigate the central angiotensinergic system. The results indicate that intracerebroventricular (i.c.v.) injections of AM and BE induced pressor elevations in all 3 strains of rats. In order to test for the possibility of spillage into peripheral vasculature, members from all 3 strains were peripherally infused with AM, BE, or 0.15 NaCl via jugular vein catheters. The SHRs were significantly more responsive to the aminopeptidases than the normotensive strains, however their overall pressor responses were only 33% of those to i.c.v. infusion. Next, in order to test the notion that these aminopeptidase inhibitors are having their effect via the central angiotensinergic system, and not some other peptidergic system, the specific angiotensin receptor antagonist, Sar1, Thr8-AII (sarthran) was employed. Intracerebroventricular pretreatment with sarthran prevented subsequent pressor responses to i.c.v. AM and BE in members of all 3 strains, thereby suggesting that these aminopeptidase inhibitors are having their effect via the central angiotensinergic system.
The present investigation examined the relative pressor potencies of intracerebroventricularly infused angiotensin (ANG) II, successively shortened COOH-terminal fragments through ANG II(5-8), and the analogues [Sar1]ANG II through [Sar1]ANG II(5-8). The results indicate that ANG II, ANG III, [Sar1]ANG II, and [Sar1]ANG III were identical with respect to pressor responses in the alert free-moving rat. In addition, ANG II(3-8) and [Sar1]ANG II(3-8) exhibited 68-70% of the activity of the above compounds, whereas the activity of the shorter COOH-terminal fragments dropped to approximately 13-35%. Pressor responses caused by each of the active forms of angiotensin could be substantially reduced by pretreatment with the specific angiotensin receptor antagonist [Sar1,Thr8]ANG II (Sarthran), suggesting either that these ligands are acting at multiple receptors for ANG II and its fragments, which are all blocked by Sarthran, or that the ligands are acting at a common receptor site. These results, coupled with other recent findings, suggest that the brain angiotensin receptor may be designed to preferentially interact with ANG II and/or ANG III or other angiotensin analogues that structurally resemble ANG III such as [Sar1]ANG II. It is concluded that ANG III's importance as a centrally active ligand has been underestimated and that ANG III may be an active form of angiotensin in the brain.
Leucine aminopeptidase M significantly reduced blood pressure for up to 40 minutes when infused intracerebroventricularly into anesthetized spontaneously hypertensive rats (SHR) from a mean +/- SEM of 190 +/- 4 to 94 +/- 7 mm Hg and also in normotensive Wistar-Kyoto (WKY) rats from 138 +/- 5 to 68 +/- 8 mm Hg. Cerebrospinal fluid levels of angiotensin II (Ang II) and III were measured by radioimmunoassay and indicated drops with leucine aminopeptidase M infusion in SHR (from 36 +/- 6 to 11 +/- 1 pg/100 microliters) and in WKY rats (from 33 +/- 9 to 13 +/- 1 pg/100 microliters). Pretreatment with the specific angiotensin receptor antagonist [Sar1, Thr8]Ang II (sarthran) significantly diminished the subsequent leucine aminopeptidase M-induced decreases in blood pressure in SHR and facilitated recovery to base level blood pressure and heart rate in blood strains. Thus, exogenous application of leucine aminopeptidase M into the brain lateral ventricles of SHR is temporarily effective at reducing blood pressure, and this effect appears dependent on the brain angiotensinergic system. This treatment also reduced blood pressure in WKY rats; however, pretreatment with sarthran was reasonably ineffective at preventing subsequent leucine aminopeptidase M-induced decreases in blood pressure.
The specific angiotensin receptor antagonist, Sar1, Thr8AII (sarthran), was infused intracerebroventricularly in alert spontaneously hypertensive rats (SHR), and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) normotensive rat strains. This resulted in a mean decrease of 35 mm Hg in the SHR group by 25 min post-infusion, and corresponding decreases in the WKY and SD rats of 13 and 15 mm Hg, respectively. A prominent transient sarthran-induced elevation in blood pressure was noted in the SHR group during the 5-min infusion. This agonistic effect was not observed in members of the WKY and SD strains. These data encourage the use of sarthran as a valuable pharmacological probe in the examination of the role of the brain renin-angiotensin system in hypertension.