Total Endovascular Aortic Replacement in Post-Dissecting Thoraco-Abdominal Aortic Aneurysm with A New Inner Branched Device.

To describe a new inner-branched device used to treat two cases of chronic post-dissection aortic thoraco-abdominal aneurysms (PD-TAAAs) after ascending aortic surgery. A 67-year-old male who had undergone an ascending aorta and arch surgical replacement and a 70-year-old male with a previous Bentall procedure for acute type A aortic dissection were admitted at our department with a PD-TAAA diagnosis. Both patients were defined unfit for open surgery by a multidisciplinary team and a totally percutaneous endovascular repair was planned. A prophylactic cerebro-spinal fluid drainage was applied and at least one hypogastric artery was targeted for salvage in order to reduce the risk of spinal cord ischemia. A new inner branch device by Jotec® (GmbH/ Criolife; Hechingen, Germany/Kennesaw, Georgia) was implanted. A TEVAR and a standard EVAR completed the procedures and a double barrel technique was performed in order to achieve the preservation of the selected hypogastric artery. In both patients the complete technical success was achieved. The postoperative period was uneventful and the patients were discharged on the 6th and 7th postoperative day, respectively. The triple-phase angio-CT performed at 6 months showed the complete false lumen exclusion and the patency of the endografts and of the target visceral vessels. The total endovascular treatment of PD-TAAAs is a fascinating technique with encouraging results in experienced centers. Inner branched devices may expand the field of application of this new technology. More data are required to evaluate mid- and long-term results.

Therapeutic potential of NADPH oxidase 1/4 inhibitors.

The NADPH oxidase (NOX) family of enzymes produces ROS as their sole function and is becoming recognized as key modulators of signal transduction pathways with a physiological role under acute stress and a pathological role after excessive activation under chronic stress. The seven isoforms differ in their regulation, tissue and subcellular localization and ROS products. The most studied are NOX1, 2 and 4. Genetic deletion of NOX1 and 4, in contrast to NOX2, has revealed no significant spontaneous pathologies and a pathogenic relevance of both NOX1 and 4 across multiple organs in a wide range of diseases and in particular inflammatory and fibrotic diseases. This has stimulated interest in NOX inhibitors for therapeutic application. GKT136901 and GKT137831 are two structurally related compounds demonstrating a preferential inhibition of NOX1 and 4 that have suitable properties for in vivo studies and have consequently been evaluated across a range of disease models and compared with gene deletion. In contrast to gene deletion, these inhibitors do not completely suppress ROS production, maintaining some basal level of ROS. Despite this and consistent with most gene deletion studies, these inhibitors are well tolerated and slow or prevent disease progression in a range of models of chronic inflammatory and fibrotic diseases by modulating common signal transduction pathways. Clinical trials in patients with GKT137831 have demonstrated excellent tolerability and reduction of various markers of chronic inflammation. NOX1/4 inhibition may provide a safe and effective therapeutic strategy for a range of inflammatory and fibrotic diseases. LINKED ARTICLES: This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.

[Investigations for esophageal motility and reflux]. / Investigations oesophagiennes: motilité oesophagienne et reflux gastro-oesophagien.

High resolution manometry represents an interesting technological advance, facilitating the procedure, a continuous recording of the peristalsis on a single image, a user-friendly reading of the spatio-temporal relationship of the peristaltic waves, and the identification of suspended focal abnormalities. Telemetric pH-metry, performed by insertion of a wireless capsule directly in the oesophagus, now remplaces conventional pH-metry, which requires a naso-oesophageal line. The main acquisition in 2008 is, however, the advent of oesophageal pH-impedancemetry. This test permits to establish a time relation between the patient's symptoms and reflux episodes, acidic as well as pH-neutral ones. This novel technic is useful for patients that remain symptomatic despite anti-secretory therapy, for patients with atypical symptoms and for those with extra-digestive symptoms.

Electrical stimulation induces propagated colonic contractions in an experimental model.

BACKGROUND: Direct colonic electrical stimulation may prove to be a treatment option for specific motility disorders such as chronic constipation. The aim of this study was to provoke colonic contractions using electrical stimulation delivered from a battery-operated device. METHODS: Electrodes were inserted into the caecal seromuscular layer of eight anaesthetized pigs. Contractions were induced by a neurostimulator (Medtronic 3625). Caecal motility was measured simultaneously by video image analysis, manometry and a technique assessing colonic transit. RESULTS: Caecal contractions were generated using 8-10 V amplitude, 1000 micros pulse width, 120 Hz frequency for 10-30 s, with an intensity of 7-15 mA. The maximal contraction strength was observed after 20-25 s. Electrical stimulation was followed by a relaxation phase of 1.5-2 min during which contractions propagated orally and aborally over at least 10 cm. Spontaneous and stimulated caecal motility values were significantly different for both intraluminal pressure (mean(s.d.) 332(124) and 463(187) mmHg respectively; P < 0.001, 42 experiments) and movement of contents (1.6(0.9) and 3.9(2.8) mm; P < 0.001, 40 experiments). CONCLUSION: Electrical stimulation modulated caecal motility, and provoked localized and propagated colonic contractions.

Management of faecal incontinence and constipation in adults with central neurological diseases.

BACKGROUND: People with neurological disease have a much higher risk of both faecal incontinence and constipation than the general population. There is often a fine line between the two conditions, with any management intended to ameliorate one risking precipitating the other. Bowel problems are observed to be the cause of much anxiety and may reduce quality of life in these people. Current bowel management is largely empirical with a limited research base. OBJECTIVES: To determine the effects of management strategies for faecal incontinence and constipation in people with neurological diseases affecting the central nervous system. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 26 January 2005), the Cochrane Central Register of Controlled Trials (Issue 2, 2005), MEDLINE (January 1966 to May 2005), EMBASE (January 1998 to May 2005) and all reference lists of relevant articles. SELECTION CRITERIA: All randomised or quasi-randomised trials evaluating any types of conservative or surgical measure for the management of faecal incontinence and constipation in people with neurological diseases were selected. Specific therapies for the treatment of neurological diseases that indirectly affect bowel dysfunction were also considered. DATA COLLECTION AND ANALYSIS: Two reviewers assessed the methodological quality of eligible trials and two reviewers independently extracted data from included trials using a range of pre-specified outcome measures. MAIN RESULTS: Ten trials were identified by the search strategy, most were small and of poor quality. Oral medications for constipation were the subject of four trials. Cisapride does not seem to have clinically useful effects in people with spinal cord injuries (three trials). Psyllium was associated with increased stool frequency in people with Parkinson's disease but did not alter colonic transit time (one trial). Prucalopride, an enterokinetic did not demonstrate obvious benefits in this patient group (one study). Some rectal preparations to initiate defaecation produced faster results than others (one trial). Different time schedules for administration of rectal medication may produce different bowel responses (one trial). Mechanical evacuation may be more effective than oral or rectal medication (one trial). There appears to be a benefit to patients in one-off educational interventions from nurses. The clinical significance of any of these results is difficult to interpret. AUTHORS' CONCLUSIONS: There is still remarkably little research on this common and, to patients, very significant condition. It is not possible to draw any recommendation for bowel care in people with neurological diseases from the trials included in this review. Bowel management for these people must remain empirical until well-designed controlled trials with adequate numbers and clinically relevant outcome measures become available.

[Non-surgical treatment of acute and late radiation proctitis]. / Traitement non chirurgical des rectites postactiniques ou radiques chroniques.

Pelvic external radiotherapy with or without brachytherapy plays an important role in the management of pelvic cancers. Despite recent technical innovations including conformal three-dimensional (3D) external beam radiotherapy and more recently intensity modulated radiotherapy (IMRT), local side effects can occur secondary to normal tissue damage caused by ionising radiation. Morbidity depends on the anatomic position of the rectum within the pelvis and the fast turnover rate of the mucosa, as well as the characteristics of the radiation treatment and patient co-morbidities. Medical management is sometimes complex and merits herein a short review.

Radial distribution of dilated intercellular spaces of the esophageal squamous epithelium in patients with reflux disease exhibiting discrete endoscopic lesions.

INTRODUCTION: Dilatation of intercellular spaces of the esophageal squamous epithelium has been suggested as a marker of early acid reflux-induced damage. This change is a potentially useful addition to histomorphological changes that represent so called minimal endoscopic lesions. We have assessed dilatation of intercellular spaces with regard to: (1) interobserver variability, and (2) whether the incidence of this varies between 'red streaks' and the adjacent normal looking squamous epithelium. METHODS: Esophageal biopsies from 44 patients with chronic gastro-esophageal reflux (GERD) were evaluated. At endoscopy, these patients had one or more red streaks on the tops of the mucosal folds in the distal esophagus. Biopsies were taken from the red streaks and from the normal-appearing mucosa 1 cm lateral to the red streaks. Biopsies were assessed in a blinded fashion by two independent pathologists (MV & RF). Criteria for assessing intercellular space dilatation were evaluated and agreed on prior to the study. RESULTS: Good interobserver agreement was recorded (kappa = 0.82 at the streaks and 0.77 for the control tissues) for absence/presence of intercellular space dilatation. Red streak and control biopsies differed significantly (p = 0.0001), with respect to presence of dilated intercellular spaces, with 90.5 % of the former demonstrating this as present compared to 56.1% in the controls. CONCLUSION: This study supports the concept that esophageal mucosal minimal changes due to reflux is localised and that dilatation of intercellular spaces is an early sign of reflux-induced epithelial damage. The low interobserver variability in the assessment of intercellular space dilatation suggests that this may be a useful variable for assessment of early signs of acid-reflux induced damage to the squamous epithelium of the esophagus by use of light microscopy.

[Abdominal pain and recurrent cholestatic jaundice]. / Douleurs abdominales et ictère cholestatique récidivant.

A 70 year old heart and renal transplanted man was hospitalized twice for acute abdominal pain with jaundice, inflammatory syndrome and cholestasis following colchicine therapy. All signs and symptoms abated after colchicine's withdrawal. Because the investigations remained negative and the temporal relationship positive, an adverse drug reaction to colchicine was considered possible.

The clinical course of fistulating Crohn's disease.

AIM: To determine the clinical characteristics, management and outcome of Crohn's fistulas from the time of first presentation. METHODS: Patients treated for fistulas 6 years previously were assessed for disease demographics, fistula characteristics and treatment from first presentation to final follow-up. RESULTS: Eighty-seven patients with active Crohn's fistulas were evaluated. The median age was 35 years and the median duration of Crohn's disease was 8 years at study entry. Disease was ileo-colonic or colonic in 85%, and 65% had rectal involvement. A single fistula was present in one-third and multiple fistulas in two-thirds; 65% of fistulas were perianal; 80% of fistulas were complex. After a median follow-up from the last treatment of 5.9 years, 68% of patients showed healing of all fistulas, 18% showed healing of some fistulas and 14% showed no healing of fistulas. The fistula site did not influence healing. Perianal and recto-vaginal fistulas took a median of 2.6 years to heal. Half of the complex fistulas required a stoma, resection or proctectomy. CONCLUSIONS: Healing is usually achieved. However, morbidity is great and healing is slow. Proctectomy is required in one-fifth of patients, and perineal healing is often slow. Defining the perianal fistula anatomy as complex or simple determines the likelihood of healing and the type of surgical approach required.

Response of fistulating Crohn's disease to infliximab treatment assessed by magnetic resonance imaging.

AIMS: To assess fistula track healing after infliximab treatment using magnetic resonance imaging. METHODS: Magnetic resonance imaging and clinical evaluation were performed before and after three infliximab infusions given over a 6-week period. Magnetic resonance images were evaluated for abscesses and fistula tracks. Paired magnetic resonance image examinations were rated 'better', 'unchanged' or 'worse'. Magnetic resonance imaging and clinical outcomes were then compared. RESULTS: Of the 12 referred patients, pre-treatment magnetic resonance imaging detected abscesses in three (two not treated). Of the 10 treated patients, seven had peri-anal fistulas, two of whom also had recto-vaginal fistulas, and three had abdominal wall entero-cutaneous fistulas. After infliximab, four were in remission, one had a response and five were non-responders. One developed a peri-anal abscess. Magnetic resonance imaging improved in six, was unchanged in two and was worse in two. In four of the six with improvement in magnetic resonance imaging, the fistula track resolved, but two of these had clinically persistent entero-cutaneous fistulas. The clinical outcome and magnetic resonance imaging correlated in seven of the 10 patients; in three (two entero-cutaneous and one peri-anal), there was discordance. CONCLUSIONS: Magnetic resonance imaging identifies clinically silent sepsis. Fistulas may persist despite clinical remission. Clinical response to infliximab and clinical correlation with magnetic resonance imaging were poor in patients with abdominal entero-cutaneous fistulas.

Management of faecal incontinence and constipation in adults with central neurological diseases.

BACKGROUND: People with neurological disease have a much higher risk of both faecal incontinence and constipation than the general population. There is often a fine dividing line between the two conditions, with any management intended to ameliorate, one risking precipitating the other. Bowel problems are observed to be the cause of much anxiety and may reduce quality of life in these people. Current bowel management is largely empirical with a limited research base. OBJECTIVES: To determine the effects of management strategies for faecal incontinence and constipation in people with neurological diseases affecting the central nervous system. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Trials Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE and all reference lists of relevant articles. Date of the most recent searches: May 2000. SELECTION CRITERIA: All randomised or quasi-randomised trials evaluating any types of conservative, or surgical measure for the management of faecal incontinence and constipation in people with neurological diseases were selected. Specific therapies for the treatment of neurological diseases that indirectly affect bowel dysfunction have also been considered. DATA COLLECTION AND ANALYSIS: All three reviewers assessed the methodological quality of eligible trials and two reviewers independently extracted data from included trials using a range of pre-specified outcome measures. MAIN RESULTS: Only seven trials were identified by the search strategy and all were small and of poor quality. Oral medications for constipation were the subject of four trials. Cisapride does not seem to have clinically useful effects in people with spinal cord injuries (two trials). Psyllium was associated with increased stool frequency in people with Parkinson's disease but not altered colonic transit time (one trial). Some rectal preparations to initiate defecation produced faster results than others (one trial). Different time schedules for administration of rectal medication may produce different bowel responses (one trial). Mechanical evacuation may be more effective than oral or rectal medication (one trial). The clinical significance of any of these results is difficult to interpret. REVIEWER'S CONCLUSIONS: It is not possible to draw any recommendation for bowel care in people with neurological diseases from the trials included in this review. Bowel management for these people must remain empirical until well-designed controlled trials with adequate numbers and clinically relevant outcome measures become available.

Red streaks in the oesophagus in patients with reflux disease: is there a histomorphological correlate?

BACKGROUND: The Los Angeles classification of reflux oesophagitis includes sharply demarcated areas of erythema without any associated slough within the definition of reflux-induced mucosal breaks, though there is uncertainty as to whether these "red streaks" actually represent such a mucosal lesion. This study evaluates the histopathology of these red streaks. METHODS: Forty patients with one or more red streaks on the tops of the mucosal folds in the distal oesophagus were included in a multinational, multicentre prospective study. All patients were referred for upper gastrointestinal endoscopy to investigate chronic heartburn and acid regurgitation. Biopsies were taken from the red streaks and from control biopsies from more normal appearing mucosa 1 cm lateral to the red streaks. A two-sided probability test using normal approximation assessed differences in the histological findings at the two biopsy locations. RESULTS: Compared to control biopsies, biopsies of red streaks had a significantly thicker basal cell layer (mean +/- s 41% +/- 32% versus 18% +/- 23% of mucosal thickness, P=0.001) and longer papillae (mean +/- s 71% +/- 19% versus 49% +/- 24% of mucosal thickness, P= 0.001). Of the red streak biopsies, 25% had either newly re-epithelized lesions or granulation tissue beneath squamous epithelium. Only 10% of the control biopsies had moderate or more marked regenerative changes (based on elongation of papillae and basal cell hyperplasia), compared to 65.1% of red streak biopsies. Of the biopsies from the red streak itself, 7% showed no abnormality and 27.9% only slight changes. In comparison, 25% of the biopsies from control biopsies showed no regenerative changes and 62.5% only slight change due to gastro-oesophageal reflux disease. CONCLUSION: The histomorphological counterpart to the endoscopically visible red streaks of the distal oesophagus is marked regenerative changes of the squamous epithelium and/or capillary rich granulation tissue beneath the squamous epithelium. Red streaks are validated as being indicative of acid/peptic mucosal injury, but they do not satisfy a strict definition of a mucosal break.

Patient satisfaction after biofeedback for constipation and pelvic floor dyssynergia.

BACKGROUND: Patients referred for chronic constipation frequently report symptoms of straining, feeling of incomplete evacuation, or the need to facilitate defecation digitally (dyschezia). When such patients show manometric evidence of inappropriate contraction or failure to relax the pelvic floor muscles during attempts to defecate, they are diagnosed as having pelvic floor dyssynergia (Rome I). AIMS: To evaluate long-term satisfaction of patients with pelvic floor dyssynergia after biofeedback. PATIENTS: Forty-one consecutive patients referred for chronic constipation at an outpatient gastrointestinal unit and diagnosed as having pelvic floor dyssynergia who completed a full course of biofeedback. METHODS: Data have been collected using a standardised questionnaire. A questionnaire survey of patients' satisfaction rate and requirement of aperients was undertaken. RESULTS: Mean age and symptom duration were respectively 41 and 20 years. Half of patients reported fewer than 3 bowel motions per week. Patients were treated with a mean of 5 biofeedback sessions. At the end of the therapy pelvic floor dyssynergia was alleviated in 85% of patients and 49% were able to stop all aperients. Satisfaction was maintained at follow-up telephone interviews undertaken after a mean period of 2 years, as biofeedback was helpful for 79% of patients and 47% still abstained from intake of aperients. CONCLUSIONS: Satisfaction after biofeedback is high for patients referred for chronic constipation and diagnosed with pelvic floor dyssynergia. Biofeedback improves symptoms related to dyschezia and reduces use of aperients.

Exacerbation of chronic renovascular hypertension and acute renal failure in heme oxygenase-1-deficient mice.

Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Because of properties of HO and its products, we hypothesized that HO would be important for the regulation of blood pressure and ischemic injury. We studied chronic renovascular hypertension in mice deficient in the inducible isoform of HO (HO-1) using a one kidney-one clip (1K1C) model of disease. Systolic blood pressure was not different between wild-type (HO-1(+/+)), heterozygous (HO-1(+/-)), and homozygous null (HO-1(-/-)) mice at baseline. After 1K1C surgery, HO-1(+/+) mice developed hypertension (140+/-2 mm Hg) and cardiac hypertrophy (cardiac weight index of 5.0+/-0.2 mg/g) compared with sham-operated HO-1(+/+) mice (108+/-5 mm Hg and 4.1+/-0.1 mg/g, respectively). However, 1K1C produced more severe hypertension (164+/-2 mm Hg) and cardiac hypertrophy (6.9+/-0.6 mg/g) in HO-1(-/-) mice. HO-1(-/-) mice also experienced a high rate of death (56%) within 72 hours after 1K1C surgery compared with HO-1(+/+) (25%) and HO-1(+/-) (28%) mice. Assessment of renal function showed a significantly higher plasma creatinine in HO-1(-/-) mice compared with HO-1(+/-) mice. Histological analysis of kidneys from 1K1C HO-1(-/-) mice revealed extensive ischemic injury at the corticomedullary junction, whereas kidneys from sham HO-1(-/-) and 1K1C HO-1(+/-) mice appeared normal. Taken together, these data suggest that chronic deficiency of HO-1 does not alter basal blood pressure; however, in the 1K1C model an absence of HO-1 leads to more severe renovascular hypertension and cardiac hypertrophy. Moreover, renal artery clipping leads to an acute increase in ischemic damage and death in the absence of HO-1.

Pathophysiology and management of bowel dysfunction in multiple sclerosis.

The prevalence of bowel dysfunction in multiple sclerosis (MS) patients is higher than in the general population. Up to 70% of patients complain of constipation or faecal incontinence, which may also coexist. This overlap can relate to neurological disease affecting both the bowel and the pelvic floor muscles, or to treatments given. Bowel dysfunction is a source of considerable ongoing psychosocial disability in many patients with MS. Symptoms related to the bladder and the bowel are rated by patients as the third most important, limiting their ability to work, after spasticity and incoordination. Bowel management in patients with MS is currently empirical. Although general recommendations include maintaining a high fibre diet, high fluid intake, regular bowel routine, and the use of enemas or laxatives, the evidence to support the efficacy of these recommendations is scant. This review will examine the current state of knowledge regarding the pathophysiological mechanisms underlying bowel dysfunction in MS, outline the importance of proper clinical assessment of constipation and faecal incontinence during the diagnostic work-up, and propose various management possibilities. In the absence of clinical trial data on bowel management in MS, these should be considered as a consensus on clinical practice from a team specialized in bowel dysfunction.

Favourable effect of an acidified milk (LC-1) on Helicobacter pylori gastritis in man.

OBJECTIVE: The supernatant of Lactobacillus johnsonii La1 culture was shown to be bactericidal and to have a partial, acid-independent suppressive effect on Helicobacter pylori in humans. The aim of the present study was to investigate the effect of L. johnsonii La1-acidified milk (LC-1) on H. pylori infection. DESIGN AND METHODS: Fifty-three volunteers infected with H. pylori as determined by positive 13C-urea breath test and positive serology were randomized to receive either LC-1 or a placebo 180 ml twice a day for 3 weeks. All subjects also received clarithromycin 500 mg bid during the last two weeks of acidified milk therapy. Oesophagogastroduodenoscopy and biopsies were performed at inclusion and repeated 4-8 weeks after the end of the treatment. H. pylori infection was confirmed by urease test and histology. H. pylori density and inflammation were scored using a modified Sydney classification. RESULTS: LC-1 ingestion induced a decrease in H. pylori density in the antrum (P= 0.02) and the corpus (P= 0.04). LC-1 also reduced inflammation and gastritis activity in the antrum (P= 0.02 and P= 0.01, respectively) and of activity in the corpus (P= 0.02). Clarithromycin eradicated H. pylori in 26% of the subjects; LC-1 did not improve the antibiotic effect. CONCLUSION: These results suggest that H. pylori infection and gastritis can be down-regulated by LC-1.