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sphincter muscle [keywords]
- Transoesophageal spinal cord stimulation for motor-evoked potentials monitoring: feasibility, safety and stability† [JOURNAL ARTICLE]
- Eur J Cardiothorac Surg 2014 Dec 18.
Specificity of transcranial motor-evoked potentials (MEPs) is low because amplitude fluctuation is common, which seems due to several technical and fundamental reasons including difficulty in electrodes positioning and fixation for transcranial stimulation and susceptibility to anaesthesia. This study aimed to investigate the feasibility, safety and stability of our novel technique of transoesophageal spinal cord stimulation to improve the stability of MEPs.Ten anaesthetized adult beagle dogs were used. Transoesophageal stimulation was performed between the oesophageal luminal surface electrode (cathode) and a subcutaneous needle electrode (anode) at the fourth to fifth thoracic vertebra level. Stimulation was achieved with a train of five pulses delivered at 2.0-ms intervals. Compound muscle action potentials were recorded from four limbs and external anal sphincter muscles. Stability to anaesthetic agents was tested at varying speeds of propofol and remifentanil, and effects of varying concentration of sevoflurane inhalation were also evaluated.Transoesophageal MEPs could be recorded without difficulty in all dogs. Fluoroscopic evaluation showed that electrodes misalignment up to 5 cm cranially or caudally could be tolerated. Stimulus intensity to achieve maximum amplitude of hindlimb muscle potentials on both sides was significantly lower by transoesophageal stimulation than by transcranial stimulation (383 ± 41 vs 533 ± 121 V, P = 0.02) and had less interindividual variability. Latency of transoesophageal MEPs was shorter than that of transcranial MEPs at every recording point. No arrhythmia was provoked during stimulation. Animals that were allowed to recover showed no neurological abnormality. In the two sacrificed animals, the explanted oesophagus showed no mucosal injury. Stability to varying dose of anaesthetic agents was similar between transoesophageal and transcranial stimulation, except for the potentials of forelimbs by transoesophageal stimulation that were resistant to anaesthetic depression.Transoesophageal stimulation for MEPs monitoring was feasible without difficulty and safe. Although its stability to anaesthetic agents was similar to that of transcranial stimulation, its technical ease and small interindividual variability warrants further studies on the response to spinal cord ischaemia.
- Defining The Histopathoogical Changes Induced By Non-Ablative Radiofrequency (RF) Treatment Of Faecal Incontinence - A Blinded Assessment In An Animal Model. [JOURNAL ARTICLE]
- Colorectal Dis 2014 Dec 18.
Non-ablative radiofrequency (RF) sphincter remodeling has been used to treat gastroesophageal reflux disease (GERD) and faecal incontinence (FI). Its mechanism of action is unclear. We aimed to investigate the histomorphological and pathophysiological changes to internal (IAS) and external anal sphincter (EAS) following RF.An experimental FI model was created in 12 female pigs: eight underwent RF 6 weeks following induction of FI (FI+RF) and four were untreated (UFI). Four animals served as controls (CG). Two blinded pathologists examined all H&E and trichrome stained slides.Compared with the UFI group, histological examination of the internal anal sphincter (IAS) in the FI+RF group demonstrated an increased smooth muscle (SM)/connective tissue ratio (77.2% vs. 68.1% p <0.05) and increased collagen-I compared with collagen-III content (67.2% vs. 54.9% [p<0.001]). The RF+FI group exhibited greater SM bundle thickness compared with the UFI group (SM width: 486.93 vs. 338.59 um; p<0.01 and height: 4384.4 vs. 3321.0 um; p<0.05). The external anal sphincter (EAS) of the FI+RF animals showed a significantly higher Type I/II fibre ratio (33.5% vs. 25.2%; p=0.023) and fibre type I diameter (67.2 vs. 59.7um; p<0.001) compared with the UFI group. Post-RF manometry showed higher basal (18.8 vs. 0 mmHg) and squeeze (76.8 vs. 12.4 mmHg; p<0.05) anal pressures. After RF treatment, the number of interstitial cells of Cajal was significantly reduced compared with the UFI and CG groups [0.9 (FI+RF) vs. 6.7 (UFI) vs. 0.7 (CG)/mm(2) ; p<0.001].Non-ablative RF in an animal model appeared to induce morphological changes in the IAS and EAS leading to an anatomical state reminiscent of normal sphincter structure. This article is protected by copyright. All rights reserved.
- How I Do It: Martius Flap for Rectovaginal Fistulas. [JOURNAL ARTICLE]
- J Gastrointest Surg 2014 Dec 18.
Rectovaginal fistulas present a difficult problem that is frustrating for patients and surgeons alike. Surgical options range from collagen plugs and endorectal advancement flaps to sphincter repairs or resection with coloanal reconstruction. For recurrent or complex rectovaginal fistulas, especially in the setting of prior radiation, Crohn's disease, or large wounds, bringing in healthy tissue into the space provides an excellent opportunity for improved results. The bulbocavernosus muscle and its surrounding vascularized tissue pedicle, first described by Martius in 1928, is an excellent option for fistula closure. Surgeons caring for these patients should be aware of this technique and have it as one method in their operative armamentarium when faced with these challenging cases.
- Pelvic floor dysfunction, and effects of pregnancy and mode of delivery on pelvic floor. [REVIEW]
- Taiwan J Obstet Gynecol 2014 Dec; 53(4):452-458.
Pelvic floor dysfunction (PFD), although seems to be simple, is a complex process that develops secondary to multifactorial factors. The incidence of PFD is increasing with increasing life expectancy. PFD is a term that refers to a broad range of clinical scenarios, including lower urinary tract excretory and defecation disorders, such as urinary and anal incontinence, overactive bladder, and pelvic organ prolapse, as well as sexual disorders. It is a financial burden on the health care system and disrupts women's quality of life. Strategies applied to decrease PFD are focused on the course of pregnancy, mode and management of delivery, and pelvic exercise methods. Many studies in the literature define traumatic birth, usage of forceps, length of the second stage of delivery, and sphincter damage as modifiable risk factors for PFD. Maternal age, fetal position, and fetal head circumference are nonmodifiable risk factors. Although numerous studies show that vaginal delivery affects pelvic floor structures and their functions in a negative way, there is not enough scientific evidence to recommend elective cesarean delivery in order to prevent development of PFD. PFD is a heterogeneous pathological condition, and the effects of pregnancy, vaginal delivery, cesarean delivery, and possible risk factors of PFD may be different from each other. Observational studies have identified certain obstetrical exposures as risk factors for pelvic floor disorders. These factors often coexist; therefore, the isolated effects of these variables on the pelvic floor are difficult to study. The routine use of episiotomy for many years in order to prevent PFD is not recommended anymore; episiotomy should be used in selected cases, and the mediolateral procedures should be used if needed.
- Anatomic basis of anorectal reconstruction by dynamic graciloplasty with pudendal nerve anastomosis. [Journal Article]
- Dis Colon Rectum 2015 Jan; 58(1):104-8.
Dynamic graciloplasty has been proposed for anal reconstruction, but this method has 2 major drawbacks. First, an electrical device is required for control of the gracilis. The anastomosis with the pudendal nerve will provide more physiological control. Second, the limitation in the mobility of the muscle flap results in wrapping the anal canal with the muscle's distal portion, which is tendonlike and inelastic. Enhancing the mobility of the muscle flap will enable wrapping with the proximal, muscle-like, and extensible portion, possibly providing better sphincteric function. However, the basis for such an operative method is lacking.The aim of this study is to provide the basis for the refined method of anal sphincter reconstruction by dynamic graciloplasty with pudendal nerve anastomosis and to verify the feasibility of lengthening the nerve to the gracilis muscle flap by dissecting into the muscle belly, detaching the gracilis muscle from its origin, and enhancing the mobility of the muscle flap.This is a retrospective, descriptive study.The results from the anatomical study on 9 cadavers are reported.Tension-free anastomosis of the pudendal nerve and nerve to the gracilis was successfully performed in all the 9 cases: in 2 cases, by lengthening the nerve. The detachment of the muscle origin improved the mobility of the muscle flap, and the more proximal portion could be used for wrapping the anal canal, as confirmed in 4 cases.The limited number of cases was a shortcoming of this study.By lengthening the nerve to the muscle, the gracilis can be used for anal sphincter reconstruction with pudendal nerve anastomosis, negating the need for an electrical device. By detaching the origin of the gracilis muscle, its proximal portion can be used to wrap the anal canal, possibly enabling a longer functional canal with stronger constricting force and better vascularity. These modifications to past methods may improve fecal continence after the operation.
- Influence of Peri-duodenal Non-constrictive Cuff on the Body Weight of Rats. [JOURNAL ARTICLE]
- Obes Surg 2014 Dec 6.
Weight loss has been found to improve or resolve cardiovascular comorbidities. There is a significant need for reversible device approaches to weight loss.Non-constrictive cuff (NCC) is made of implantable silicone rubber with an internal diameter greater than the duodenum. Ten or 11 NCC were individually mounted along the duodenum from the pyloric sphincter toward the distal duodenum to cover ~22 mm in the length. Twelve Wistar rats were implanted with NCC, and six served as sham, and both groups were observed over 4 months. Six rats with implant had their NCC removed and were observed for additional 4 weeks.The food intake decreased from 40.1 to 28.1 g/day after 4 months of NCC implant. The body weight gain decreased from 1.76 to 0.46 g/day after 4 months of NCC implant. The fasting glucose decreased from 87.7 to 75.3 mg/dl at terminal day. The duodenal muscle layer covered by the NCC increased from 0.133 to 0.334 mm. After 4 weeks of NCC removal, the food intake, body weight gain, and fasting glucose recovered to 36.2, 2.51 g/day, and 83.9 mg/dl. The duodenal muscle layer covered by the NCC decreased to 0.217 mm.The NCC implant placed on the proximal duodenum is safe in rats for a 4-month period. The efficacy of the NCC implant is significant for decrease in food intake, body weight gain, and fasting glucose in a normal rat model. The removal of NCC implant confirmed a cause-effect relation with food intake and hence body weight.
- Targeted disruption of Tbc1d20 with zinc-finger nucleases causes cataracts and testicular abnormalities in mice. [JOURNAL ARTICLE]
- BMC Genet 2014 Dec 5; 15(1):135.
BackgroundLoss-of-function mutations in TBC1D20 cause Warburg Micro syndrome 4 (WARBM4), which is an autosomal recessive syndromic disorder characterized by eye, brain, and genital abnormalities. Blind sterile (bs) mice carry a Tbc1d20-null mutation and exhibit cataracts and testicular phenotypes similar to those observed in WARBM4 patients. In addition to TBC1D20, mutations in RAB3GAP1, RAB3GAP2 and RAB18 cause WARBM1-3 respectively. However, regardless of which gene harbors the causative mutation, all individuals affected with WARBM exhibit indistinguishable clinical presentations. In contrast, bs, Rab3gap1 -/- , and Rab18 -/- mice exhibit distinct phenotypes; this phenotypic variability of WARBM mice was previously attributed to potential compensatory mechanisms. Rab3gap1 -/- and Rab18 -/- mice were genetically engineered using standard approaches, whereas the Tbc1d20 mutation in the bs mice arose spontaneously. There is the possibility that another unidentified mutation within the bs linkage disequilibrium may be contributing to the bs phenotypes and thus contributing to the phenotypic variability in WARBM mice. The goal of this study was to establish the phenotypic consequences in mice caused by the disruption of the Tbc1d20 gene.ResultsThe zinc finger nuclease (ZFN) mediated genomic editing generated a Tbc1d20 c.[418_426del] deletion encoding a putative TBC1D20-ZFN protein with an in-frame p.[H140_Y143del] deletion within the highly conserved TBC domain. The evaluation of Tbc1d20 ZFN/ZFN eyes identified severe cataracts and thickened pupillary sphincter muscle. Tbc1d20 ZFN/ZFN males are infertile and the analysis of the seminiferous tubules identified disrupted acrosomal development. The compound heterozygote Tbc1d20 ZFN/bs mice, generated from an allelic bs/+ X Tbc1d20 ZFN/+ cross, exhibited cataracts and aberrant acrosomal development indicating a failure to complement.ConclusionsOur findings show that the disruption of Tbc1d20 in mice results in cataracts and aberrant acrosomal formation, thus establishing bs and Tbc1d20 ZFN/ZFN as allelic variants. Although the WARBM molecular disease etiology remains unclear, both the bs and Tbc1d20 ZFN/ZFN mice are excellent model organisms for future studies to establish TBC1D20-mediated molecular and cellular functions.
- Stress urinary incontinence animal models as a tool to study cell-based regenerative therapies targeting the urethral sphincter. [REVIEW]
- Adv Drug Deliv Rev 2014 Oct 23.
Urinary incontinence (UI) is a major health problem causing a significant social and economic impact affecting more than 200million people (women and men) worldwide. Over the past few years researchers have been investigating cell therapy as a promising approach for the treatment of stress urinary incontinence (SUI) since such an approach may improve the function of a weakened sphincter. Currently, a diverse collection of SUI animal models is available. We describe the features of the different models of SUI/urethral dysfunction and the pros and cons of these animal models in regard to cell therapy applications. We also discuss different cell therapy approaches and cell types tested in preclinical animal models. Finally, we propose new research approaches and perspectives to ensure the use of cellular therapy becomes a real treatment option for SUI.
- Expression of serotonin receptors in human lower esophageal sphincter. [JOURNAL ARTICLE]
- Exp Ther Med 2015 Jan; 9(1):49-54.
Serotonin (5-HT) is a neurotransmitter and vasoactive amine that is involved in the regulation of a large number of physiological functions. The wide variety of 5-HT-mediated functions is due to the existence of different classes of serotonergic receptors in the mammalian gastrointestinal tract and nervous system. The aim of this study was to explore the expression of multiple types of 5-HT receptor (5-HT1AR, 5-HT2AR, 5-HT3AR, 5-HT4R, 5-HT5AR, 5-HT6R and 5-HT7R) in sling and clasp fibers from the human lower esophageal sphincter (LES). Muscle strips of sling and clasp fibers from the LES were obtained from patients undergoing esophagogastrectomy, and circular muscle strips from the esophagus and stomach were used as controls. Reverse transcription-polymerase chain reaction (RT-PCR), quantitative PCR and western blotting were used to investigate the expression of the various 5-HT receptor types. Messenger RNA for all seven 5-HT receptor types was identified in the sling and clasp fibers of the LES. At the mRNA level, the expression levels were highest for 5-HT3AR and 5-HT4R, and lowest for 5-HT5AR, 5-HT6R and 5-HT7R. At the protein level, the expression levels were highest for 5-HT3AR and 5-HT4R, followed by 5-HT1AR and 5-HT2AR; 5-HT7R was also detected at a low level. The expression of 5-HT5AR and 5-HT6R proteins was not confirmed. The results indicate that a variety of 5-HT receptor types can be detected in the human LES and probably contribute to LES function.
- Mesenchymal stromal cells for sphincter regeneration. [REVIEW]
- Adv Drug Deliv Rev 2014 Oct 27.
Stress urinary incontinence (SUI), defined as the involuntary loss of considerable amounts of urine during increased abdominal pressure (exertion, effort, sneezing, coughing, etc.), is a severe problem to the individuals affected and a significant medical, social and economic challenge. SUI is associated with pelvic floor debility, absence of detrusor contraction, or a loss of control over the sphincter muscle apparatus. The pathology includes an increasing loss of muscle cells, replacement of muscular tissue with fibrous tissue, and general aging associated processes of the sphincter complex. When current therapies fail to cure or improve SUI, application of regeneration-competent cells may be an alternative therapeutic option. Here we discuss different aspects of the biology of mesenchymal stromal cells, which are relevant to their clinical applications and for regenerating the sphincter complex. However, there are reports in favor of and against cell-based therapies. We therefore summarize the potential and the risks of cell-based therapies for the treatment of SUI.