Toxins produced by the Gram-positive bacteria Clostridium botulinum cause transient chemodenervation of mammalian muscle. The toxin binds to specific proteins within cholinergic presynaptic nerve terminals which regulate the release of acetylcholine in the synaptic space resulting is loss of muscle activation and function. Local injections with botulinum toxins are currently used in humans for the treatment of disorders that benefit from prolonged neuromuscular blockade such as strabismus, blepharospasm, focal dystonias, spasticity, tremors, and anal fissures. Injections with botulinum toxin type A into the internal or external anal sphincter cause relaxation of the anal canal and allow healing of chronic anal fissures. Perineal lacerations in mares, which occur during foaling often dehisce after surgical repair due to the high pressure across the incision resulting from accumulation of feces in the rectum. We hypothesized local injections of Clostridium botulinum type B toxin into the external anal sphincter could cause a decrease in anal pressures, thus reducing the incidence of dehiscence if used before surgical repair of perineal laceration in mares. The purpose of this project was to determine the effects of BTB injection in the external anal sphincter in normal horses. Our hypothesis was that local injection of BTB would result in transient reduction of anal tone without causing clinical side effects. Peak and resting anal sphincter pressures of horses were measured with a custom made rectal probe connected to a pressure transducer. Pressures were measured before treatment and after injection with Clostridium botulinum type B toxin (BTB) or saline. Dose titration with 500, 1000, 1500 and 2500 units of BTB was completed. The horses' physical changes, behavior, and anal pressure were recorded. Injection of 1000 units of BTB produced significant reduction in peak anal pressure from days 2 to 84 when compared to control animals (P<0.05). Maximal effect of the toxin was observed within the first 15 days after injections followed by a slow return to baseline over 168 days. Injection in the anal sphincter with 2500 units of BTB in one horse produced signs of depression, generalized weakness, and dysphagia for 14 days. Clinical side effects were not observed in horses after injections with 500, 1000, or 1500 units of BTB. In summary, local injections of botulinum toxin type-B in the external anal sphincter of horses caused transient relaxation of the anus and reduction of peak anal pressures. Systemic side effects were observed in one horse, which suggested a narrow dosage range to avoid toxicity. Further research to test the effects of botulinum toxin in clinical cases is needed to determine the full potential of this treatment modality. / Master of Science

La société UroMems propose de résoudre les problèmes d’incontinence urinaire avec un nouveau sphincter urinaire artificiel, dans lequel le mécanisme de pompe manuelle utilisé dans les sphincters actuellement implantés dans de nombreux patients est remplacé par un dispositif mécatronique. Une manchette occlusive, mimant le fonctionnement du sphincter naturel, est reliée et activée par le dispositif afin d’autoriser la miction et l’incontinence du patient.Le travail de thèse s’oriente sur la compréhension et l’amélioration du sphincter artificiel. La première partie de cette étude porte sur la numérisation et la modélisation 3D de cette manchette, la caractérisation mécanique de ses différents composants et la mise en place d’un modèle éléments finis. Un banc de test sur un cas simple avec suivi par stéréo-corrélation d’images est également présenté afin de valider le comportement du modèle numérique pour un chargement simple. La deuxième partie porte sur la simulation du geste chirurgical et du fonctionnement de la manchette ainsi qu’une validation du modèle éléments finis en comparaison avec des mesures effectuées sur paillasse. La troisième partie de ce travail consiste à produire des données expérimentales sur sujet anatomique afin d’observer le fonctionnement de la manchette dans son environnement naturel. Les résultats de cette étude ont motivé l’utilisation d’un matériau fantôme (un hydrogel de Polyvinyl alcohol) dont les propriétés mécaniques sont ajustables. Une caractérisation mécanique de cet hydrogel est présentée ainsi qu’un banc d’essai servant de cas test pour la validation du modèle numérique complet. La quatrième partie propose une analyse histo-morphologique de l’urètre masculin, ainsi qu’une caractérisation mécanique complète. Les données obtenues sont ensuite intégrées au modèle éléments finis afin de simuler le fonctionnement de la manchette occlusive dans son environnement naturel. Dans la dernière partie l’outil numérique mis en place est exploité afin de proposer des pistes d’améliorations du sphincter artificiel actuel. / UroMems aims at developing a novel treatment solution for severe urinary incontinence by replacing the manual pump mechanism, which is currently considered as the gold standard and which is implanted in patients throughout the world, by a mechatronic device. An occlusive cuff that mimics the natural human sphincter is linked to the device in order to ensure continence and allow micturition.This work focuses on understanding and improving the artificial sphincter. The first part of this study aims at modeling of the occlusive cuff, characterizing the mechanical behavior of all of its components and establishing a corresponding finite element model. A bench test using digital image correlation is also presented in order to validate the behavior of the numerical model for a simple test. In the second part the implantation of the occlusive and its inflation are simulated and the model is validated by comparing its results to the data measured experimentally. The third part aims at validating the interaction between the occlusive cuff and an extraneous body in the numerical simulation. To this end the in vivo experimental behavior of the occlusive cuff is observed. The variability measured among the different subjects motivated the use of a phantom material (a Polyvinyl alcohol hydrogel) of controlled mechanical properties. A thorough mechanical characterization of the hydrogel is also presented in this part as well as a test bench used for the validation of the numerical model. The fourth part proposes a histo-morphological analysis of the male urethra and its mechanical characterization. The data obtained were then integrated to the finite element model. The last part of this work is dedicated to exploiting the finite element tool to propose design improvement of the occlusive cuff.

The diploma thesis aims to describe the functional disorders of the upper gastrointestinal tract with an emphasis on gastroesophageal reflux disease. The theoretical part describes the anatomy, pathophysiology, etiology of GERD and treatment options. In the practical part is measured postural reactivity of the diaphragm in the selected 15 probands with GERD. We measured the postural reactivity of the diaphragm using high resolution manometry in various postural situations: lying on the back with flexion of lower limbs above the surface, standing and standing on the AIREX mat, for standing patients, we used weights of 3,6 and 9 kilos inside and outside the center of gravity. Patients also completed the GERD Health-Related Quality of Life questionnaire. The measurements confirmed an increase in resting pressure in all positions except standing, which correlated with the highest occurrence of reflux episodes in standing. The results were compared with a healthy control group. The activation of the crural part of the diaphragm was the same in both groups. We found in patients with GERD decreased coordination, delayed and influent activation of the crural diaphragm. The most significant increase in pressure in GERD patients occurred in the postural position of the flexed lower limbs and in standing...

Severe perineal trauma with injury to the anal sphincter at childbirth can have a profound effect on the physical and psychological wellbeing of women. This thesis describes literature examining resulting outcomes including effects on body image. It describes patient-based outcome measures used to capture this information, and evaluation of their psychometric properties. Body Image can be defined as an individual's perceptions and feelings about their own body. There is a growing interest in how this concept can influence quality of life and psychosocial dysfunction in medical disorders. This thesis aimed to examine relationships between severity of perineal trauma, general and genital specific body image and potentially influences such as symptoms of pelvic floor dysfunction. No patient-reported outcome measure validated for use in women after anal sphincter injury exists and this thesis also aimed to psychometrically evaluate an existing electronic questionnaire, ePAQ (electronic personal assessment questionnaire), for this application. In the thesis, a retrospective review of body image and physical outcomes attending a perineal clinic shows over half of women report perceived changes in body image after anal sphincter injury, with negative effects on self-esteem. A prospective observational cohort study explored genital and general body image in primiparous women grouped according to degree of perineal trauma or caesarean delivery. Women completed the Female Genital Self Image Score, the modified Body Image Score, ePAQ and the Edinburgh Postnatal Depression Scale a mean of 15.5 weeks (standard deviation 1.6) after delivery. There were significant differences in genital body image scores between the groups, but not in general body image, with regression analysis showing the greatest influence on genital body image to be the anatomical extent of the trauma. Embedded into this study was the evaluation of reliability (internal consistency and test-retest) and validity (face, content and construct) of ePAQ in the group of women with anal sphincter tears. This thesis presents the first research to quantify issues surrounding severe perineal trauma and body image and demonstrates that more severe trauma leads to a poorer genital body image. It also reports psychometric evaluation of ePAQ in women after anal sphincter injury providing the first single instrument with validity and reliability for use in this context.

Introdução: A perda da função esfincteriana anal e a colostomia definitiva são condições socialmente incapacitantes, com grande impacto social e econômico. Não há tratamento satisfatório para estas duas condições e o transplante anorretal surge como uma alternativa para a perda da função ou do esfíncter anal propriamente dito. Objetivo: apresentar modelo experimental de autotransplante anorretal em ratos, avaliar os seus resultados clínicos e funcionais Método: 55 ratos Wistar foram divididos aleatoriamente em quatro grupos de estudo: I autotransplante anorretal ortotópico (n=13); II - autotransplante heterotópico (n=14); III - SHAM - ratos submetidos a laparotomia e incisão perianal (n=13); IV - Controle - ratos não operados (n=15). Os animais foram avaliados com parâmetros clínicos e manométricos. Os parâmetros clínicos de avaliação foram: peso, comportamento, aspecto das fezes, aspecto anal e aspecto abdominal. Os dados de avaliação clínica foram protocolados no dia do procedimento (D0), segundo dia pós-operatório (D2), sétimo (D7) e décimo quarto dias (D14). Exceto peso, todos os demais foram avaliados por escores préestabelecidos. A manometria foi usada para determinação das pressões Médias e Máximas, e realizadas no pré-operatório imediato (D0 pré), logo após o procedimento (D0 pós), no D7 e no D14. O grupo II teve avaliação manométrica apenas no D0 pré e D14. As manometrias de ratos normais foram analisadas separadamente, para determinação do perfil funcional anorretal normal. Foram também comparados os grupos I, III e IV em todos os momentos, e os quatro grupos nos momentos D0 pré e D14. Os animais foram sacrificados após 14 dias e o segmento anorretal foi analisado histologicamente. Resultados: ocorreram nove óbitos pós operatórios, 5 no grupo II e 4 no grupo I. Todos os parâmetro clínicos mostraram tendência de piora no pós-operatório precoce nos grupos transplantados. Porém, houve equiparação entre os grupos ao final do estudo. A anatomia patológica demonstrou histologia análoga entre os grupos transplantados e os controles após 14 dias. As manometrias em ratos normais tiveram média de pressões Médias de 33,7 ± 12,6 cmH2O, e de pressões Máximas de 61,2 ± 19 cmH2O. Na comparação entre os grupos I, III e IV, no D0 pós existiu queda significativa das pressões nos grupos I e III, diferentes do IV (p<0,05). No D7 observou-se recuperação de atividade manométrica do grupo I, porém estatisticamente inferior ao grupo Controle. No D14 os grupos foram estatisticamente semelhantes. Na comparação dos quatro grupos houve queda pressórica significativa no grupo II, que diferiu dos grupos controle (p<0,05). O grupo I não diferiu dos controles nem do grupo II no D14. Conclusões: 1. O modelo experimental proposto de autotransplante anorretal ortotópico e heterotópico em ratos é factível. 2. A evolução clínica e funcional do transplante anorretal demonstrou perda da função imediatamente após o transplante, com recuperação ao longo de 14 dias. 3. O transplante heterotópico teve resultados precoces piores que o ortotópico / Introduction: The loss of anal sphincter function and permanent colostomy are disabling conditions with great social and economic impact. There is no satisfactory treatment for either of these conditions and anorectal transplantation offers an alternative to the loss of function or the loss of the anal sphincter itself. Aim: To present an experimental model of anorectal autotransplantation in rats to assess the clinical and functional results. Method: 55 Wistar rats were divided randomly into four study groups: I - orthotopic anorectal autotransplantation (n=13), II - Heterotopic autotransplantation (n=14), III SHAM - Laparotomy and perianal incision (n=13), IV - Control non-operated rats (n=15). The animals were evaluated with clinical and manometric parameters. The clinical parameters of evaluation were: weight, behavior, appearance of stools, appearance of the anus and abdominal distension. Clinical trial data was collected on the day of the procedure (D0) and the second (D2), seventh (D7) and fourteenth (D14) post-operative days. All parameters, except for weight, were evaluated by pre-established scores. Manometry was used to determine the Mean and Maximum pressures, and performed immediately before (D0 pre), immediately after the procedure (D0 post), and on D7 and D14. Group II had manometric evaluation only on D0 pre and D14. The manometries of the non-operated rats were analyzed separately to determine a normal anorectal functional profile. Groups I, III and IV were also compared at all evaluation times and all four groups on D0 pre and D14. The animals were sacrificed after 14 days and the anorectal segment was examined histologically. Results: There were nine post-operative deaths, 5 in group II and 4 in group I. All clinical parameters showed a worsening trend in the early postoperative evaluation in the transplant groups. However, at the end of the study there were no significant differences between the groups. The histology of the transplanted groups and the control groups was similar after 14 days. The manometries in normal rats had an average of 33.7 ±12.6 cmH2O Mean pressure, and average Maximum pressure of 61.2 ±19 cmH2O. In the analysis of groups I, III and IV, a significant drop of pressure in groups I and III occurred at D0 post compared to group IV (p<0.05). Functional recovery of Group I was noted in D7, but statistically lower than the Control group. The three groups were statistically similar at D14. In the comparison of the four groups there was a significant pressure fall in Group II, which differed from the control groups (p<0.05). Group I did not differ from the controls or Group II in D14. Conclusions: 1.The proposed experimental orthotopic and heterotopic anorectal autotransplantation model in rats is feasible. 2. The clinical and functional outcomes demonstrated loss of function immediately after transplantation, with recovery over the course of 14 days. 3. The Heterotopic transplantation had worse early results than the orthotopic method

<p>One hundred haemorrhoid patients were compared with 300 matched control persons. Haemorrhoid symptoms and bowel symptoms were studied. Most common symptom of the patients was bleeding (44%), followed by prolapse (24%), hygiene problem (14%), pain (12%) and itching (5%). Bowel symptoms, as bloating and evacuation difficulties, possibly related to IBS, were frequent among the patients.</p><p>556 patients were operated upon with Milligan-Morgan haemorrhoidectomy. 418 (81%) answered a questionnaire on results, and on disturbances in anal continence. Totally140 (33%) reported recurrence, and 139 (33%) patients reported anal incontinence. Forty of the 139 patients associated this to the surgical procedure. Female gender was associated to increased risk of incontinence.</p><p>The 40 patients who reported incontinence, were invited to undergo ano-rectal manometry, saline infusion test, endo-anal ultrasound, proctoscopy and clinical examination. Altogether 19 patients approved to participate. Matched control subjects and 15 persons previously operated for haemorrhoids, but without symptoms of incontinence, served as two reference groups. Incontinence score and saline infusion test showed significantly poorer continence in the patient group. Endo-anal ultrasound showed injury to the external sphincter in 20% of the patients. Anal pressure was slightly lower in the patient group, but the difference was not significant. </p><p>Totally 225 patients were randomised to Milligan-Morgan or Ferguson haemorrhoidectomy. Primary aim was to study changes in anal continence. Other aims were to study postoperative pain, wound healing, complications, patient satisfaction and recurrence and changes in bowel function. Patients in the Ferguson group reported, slightly quicker wound healing (P=0.06). Postoperative pain was equal, as was rate of complications. After one year the Ferguson group reported lower incontinence score, and more satisfied patients. Recurrence rate was equal, 15-17%. Most bowel symptoms were reduced one year after surgery.</p><p>In conclusion, functional bowel symptoms are common in haemorrhoid patients. Haemorrhoidectomy is associated with risk for incontinence in 5-10% of patients and females are at greater risk. A proportion of the patients who claim postoperative incontinence have physiological signs of sphincter incompetence, and external sphincter injuries are observed in those patients. Ferguson haemorrhoidectomy results in better anal continence and more satisfied patients. </p>

One hundred haemorrhoid patients were compared with 300 matched control persons. Haemorrhoid symptoms and bowel symptoms were studied. Most common symptom of the patients was bleeding (44%), followed by prolapse (24%), hygiene problem (14%), pain (12%) and itching (5%). Bowel symptoms, as bloating and evacuation difficulties, possibly related to IBS, were frequent among the patients. 556 patients were operated upon with Milligan-Morgan haemorrhoidectomy. 418 (81%) answered a questionnaire on results, and on disturbances in anal continence. Totally140 (33%) reported recurrence, and 139 (33%) patients reported anal incontinence. Forty of the 139 patients associated this to the surgical procedure. Female gender was associated to increased risk of incontinence. The 40 patients who reported incontinence, were invited to undergo ano-rectal manometry, saline infusion test, endo-anal ultrasound, proctoscopy and clinical examination. Altogether 19 patients approved to participate. Matched control subjects and 15 persons previously operated for haemorrhoids, but without symptoms of incontinence, served as two reference groups. Incontinence score and saline infusion test showed significantly poorer continence in the patient group. Endo-anal ultrasound showed injury to the external sphincter in 20% of the patients. Anal pressure was slightly lower in the patient group, but the difference was not significant. Totally 225 patients were randomised to Milligan-Morgan or Ferguson haemorrhoidectomy. Primary aim was to study changes in anal continence. Other aims were to study postoperative pain, wound healing, complications, patient satisfaction and recurrence and changes in bowel function. Patients in the Ferguson group reported, slightly quicker wound healing (P=0.06). Postoperative pain was equal, as was rate of complications. After one year the Ferguson group reported lower incontinence score, and more satisfied patients. Recurrence rate was equal, 15-17%. Most bowel symptoms were reduced one year after surgery. In conclusion, functional bowel symptoms are common in haemorrhoid patients. Haemorrhoidectomy is associated with risk for incontinence in 5-10% of patients and females are at greater risk. A proportion of the patients who claim postoperative incontinence have physiological signs of sphincter incompetence, and external sphincter injuries are observed in those patients. Ferguson haemorrhoidectomy results in better anal continence and more satisfied patients.

Thèse d'exercice : Médecine. Gynécologie-obstétrique : Paris 12 : 2007. / Titre provenant de l'écran-titre. 65 f. : ill. Bibliogr. f. 57-64.

Thesis--Odense. / Summary in Danish. Includes bibliographical references (p. 136-[147]) and index.

Im Zeitraum von 1999 bis 2009 wurde am Universitätsklinikum Göttingen bei 65 Patienten im Rahmen einer Harninkontinenztherapie ein operativer Eingriff mit einem künstlichen Sphinktersystem durchgeführt. Die vorliegende Arbeit untersucht den Erfolg dieser Behandlungsmethode. Dazu wurden sowohl präoperative Befunde aus den Patientenakten erhoben als auch der postoperative Verlauf bewertet. Mit Hilfe zweier validierter Fragebögen sowie selbst formulierter Zusatzfragen, die sich mit der allgemeinen Lebensqualität der behandelten Patienten, mit der Inkontinenzsymptomatik und der die Miktion betreffenden Lebensqualität beschäftigen, sollen sowohl die subjektive Patientenzufriedenheit als auch Veränderungen bezüglich der präoperativen und postoperativen Kontinenzsituation der Betroffenen evaluiert werden. Die Schwerpunkte der Auswertung betreffen die postoperative Kontinenzsituation, die Komplikationsrate und die Zufriedenheit der Patienten mit dem Behandlungserfolg. Die Ergebnisse werden mit bereits veröffentlichten Literaturangaben verglichen und diskutiert.