A New Appendicostomy Technique to Prevent Stomal Stenosis.

PURPOSE: Stomal stenosis has been reported to occur in 12% to 45% of patients following Malone antegrade continence enema and Mitrofanoff appendicostomy. The standard stoma technique entails excision of the distal appendix. We evaluated a novel technique with preservation of the appendiceal tip and vessels, and opening the lumen in a more proximal and vascular area to determine whether the incidence of stenosis would be decreased. MATERIALS AND METHODS: Medical records of patients who underwent appendicostomy for Malone antegrade continence enema or urinary diversion were retrospectively evaluated. We included cases with a minimum of 1 year of followup and those in which the distal portion of a complete appendix was oriented for use as the stomal end in the umbilicus. Variables such as age, gender, body mass index, antegrade continence enema or urinary diversion, open or laparoscopic approach, cecal and appendiceal adhesions, retrocecal position, cecal imbrication, technique and stenosis were recorded. Cox proportional hazards analyses were performed to determine association of covariates. RESULTS: A total of 123 patients met inclusion criteria. The incidence of stenosis following standard stoma technique was 13% (12 of 93 patients) with a median followup of 9.4 years. Of these cases 75% occurred within 1 year of surgery. Stomal stenosis did not occur after the new stoma technique in 30 patients with a median followup of 3.3 years. Only technique cohort (standard vs new) was associated with stenosis (p=0.04). CONCLUSIONS: Stomal stenosis of appendicostomy may be lessened by preservation of the distal appendiceal vasculature and tip, and opening the lumen in a more proximal location.

Preventive effect of mesenchymal stem cell culture supernatant on luminal stricture after endoscopic submucosal dissection in the rectum of pigs.

BACKGROUND: Mesenchymal stem cells (MSCs) are valuable in regenerative medicine, and MSC culture supernatant (MSC-CS) reportedly inhibits inflammation and fibrosis. We investigated whether colorectal luminal stricture develops after circumferential endoscopic submucosal dissection (ESD) in the colorectum, and whether the development of luminal stricture could be prevented by using MSC-CS enema. METHODS: In the first experiment, we performed circumferential ESD in the rectums or distal colons of pigs (n = 4 in each group). We sacrificed the pigs on Day 22 and measured the degree of luminal stricture. In the second experiment, we performed circumferential ESD in the rectums of pigs and administered an MSC-CS gel or a control gel enema after ESD for 4 days. We sacrificed the pigs on Day 8 (n = 3 in each group) or 22 (n = 3 in each group) to measure the degree of luminal stricture, and performed histological analysis. RESULTS: Severe luminal stricture was observed in the rectum but not in the distal colon. Moreover, fiber accumulation in the submucosa and hypertrophy of the muscularis propria were observed in the rectum but not in the distal colon. The degree of luminal stricture in the rectum was significantly lower in the MSC-CS group than in the control group. Furthermore, MSC-CS attenuated myofibroblast activation and hypertrophy of the muscularis propria on Day 22, and reduced inflammatory cell infiltration on Day 8. CONCLUSIONS: Luminal stricture after ESD developed only in the rectum because of the difference in myofibroblast activation and fiber accumulation. In addition, MSC-CS enema prevented luminal stricture after ESD, possibly by inhibiting the inflammatory reaction and fibrosis.

The pathogenesis of hemodialysis vascular access failure and systemic therapies for its prevention: Optimism unfulfilled.

In patients receiving hemodialysis, the provision of safe and effective vascular access using an arteriovenous fistula or graft is regarded as a critical priority by patients and health professionals. Vascular access failure is associated with morbidity and mortality, such that strategies to prevent these outcomes are essential. Inadequate vascular remodeling and neointimal hyperplasia resulting in stenosis and frequently thrombosis are critical to the pathogenesis of access failure. Systemic medical therapies with pleiotropic effects including antiplatelet agents, omega-3 polyunsaturated fatty acids (fish oils), statins, and inhibitors of the renin-angiotensin-aldosterone system (RAAS) may reduce vascular access failure by promoting vascular access maturation and reducing stenosis and thrombosis through antiproliferative, antiaggregatory, anti-inflammatory and vasodilatory effects. Despite such promise, the results of retrospective analyses and randomized controlled trials of these agents on arteriovenous fistula and graft outcomes have been mixed. This review describes the current understanding of the pathogenesis of arteriovenous fistula and graft failure, the biological effects of antiplatelet agents, fish oil supplementation, RAAS blockers and statins that may be beneficial in improving vascular access survival, results from clinical trials that have investigated the effect of these agents on arteriovenous fistula and graft outcomes, and it explores future therapeutic approaches combining these agents with novel treatment strategies.

Effect of Fish Oil Supplementation and Aspirin Use on Arteriovenous Fistula Failure in Patients Requiring Hemodialysis: A Randomized Clinical Trial.

Importance: Vascular access dysfunction is a leading cause of morbidity and mortality in patients requiring hemodialysis. Arteriovenous fistulae are preferred over synthetic grafts and central venous catheters due to superior long-term outcomes and lower health care costs, but increasing their use is limited by early thrombosis and maturation failure. ω-3 Polyunsaturated fatty acids (fish oils) have pleiotropic effects on vascular biology and inflammation and aspirin impairs platelet aggregation, which may reduce access failure. Objective: To determine whether fish oil supplementation (primary objective) or aspirin use (secondary objective) is effective in reducing arteriovenous fistula failure. Design, Setting, and Participants: The Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) study was a randomized, double-blind, controlled clinical trial that recruited participants with stage 4 or 5 chronic kidney disease from 2008 to 2014 at 35 dialysis centers in Australia, Malaysia, New Zealand, and the United Kingdom. Participants were observed for 12 months after arteriovenous fistula creation. Interventions: Participants were randomly allocated to receive fish oil (4 g/d) or matching placebo. A subset (n = 406) was also randomized to receive aspirin (100 mg/d) or matching placebo. Treatment started 1 day prior to surgery and continued for 12 weeks. Main Outcomes and Measures: The primary outcome was fistula failure, a composite of fistula thrombosis and/or abandonment and/or cannulation failure, at 12 months. Secondary outcomes included the individual components of the primary outcome. Results: Of 1415 eligible participants, 567 were randomized (359 [63%] male, 298 [53%] white, 264 [47%] with diabetes; mean [SD] age, 54.8 [14.3] y). The same proportion of fistula failures occurred in the fish oil and placebo arms (128 of 270 [47%] vs 125 of 266 [47%]; relative risk [RR] adjusted for aspirin use, 1.03; 95% CI, 0.86-1.23; P = .78). Fish oil did not reduce fistula thrombosis (60 [22%] vs 61 [23%]; RR, 0.98; 95% CI, 0.72-1.34; P = .90), abandonment (51 [19%] vs 58 [22%]; RR, 0.87; 95% CI, 0.62-1.22; P = .43), or cannulation failure (108 [40%] vs 104 [39%]; RR, 1.03; 95% CI, 0.83-1.26; P = .81). The risk of fistula failure was similar between the aspirin and placebo arms (87 of 194 [45%] vs 83 of 194 [43%]; RR, 1.05; 95% CI, 0.84-1.31; P = .68). Conclusions and Relevance: Neither fish oil supplementation nor aspirin use reduced failure of new arteriovenous fistulae within 12 months of surgery. Trial Registration: anzctr.org.au Identifier: CTRN12607000569404.

Omega-3 fatty acid supplement prevents development of intracranial atherosclerosis.

OBJECTIVES: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and, in particular, has been implicated as a leading cause of recurrent ischemic stroke. We adapted a rat model of atherosclerosis to study brain intracranial atherosclerosis, and further investigated the effect of omega-3 fatty acids (O3FA) in attenuating development of ICAS. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were divided into control normal-cholesterol or high-cholesterol diet groups with or without O3FA for up to 6weeks. During the first 2weeks, NG-nitro-l-arginine methyl ester (l-NAME, 3mg/mL) was added to the drinking water of the high-cholesterol groups. The rats received supplementation with O3FA (5mg/kg/day) by gavages. Blood lipids including low density lipoprotein (LDL), cholesterol (CHO), triglycerides (TG) and high density lipoprotein (HDL) were measured at 3 and 6weeks. The lumen of middle cerebral artery (MCA) and the thickness of the vessel wall were assessed. Inflammatory molecular markers were assessed by Western blot. RESULTS: A high-cholesterol diet exhibited a significant increase in the classic blood markers (LDL, CHO, and TG) for atherosclerosis, as well as a decrease in HDL. These markers were found to be progressively more severe with time. Lumen stenosis and intimal thickening were increased in MCA. O3FA showed attenuation of blood lipids with an absence of morphological changes. O3FA significantly reduced the inflammatory marker CD68 in MCA and prevented monocyte chemotactic protein (MCP-1) and interferon-γ (IFN-γ) expression in the brain. O3FA similarly decreased inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6), markers affiliated with monocyte activity in atherosclerosis. Furthermore, O3FA significantly inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1), a marker for endothelial activation. Lastly, O3FA increased ATP-binding cassette transporter A1 (ABCA1) protein expression via silent information regulator 1 (SIRT1) activation, thus increasing cholesterol efflux from macrophages to HDL. CONCLUSIONS: Long-term O3FA dietary supplementation prevents the development of intracranial atherosclerosis. This O3FA effect appears to be mediated by its prevention of macrophage infiltration into the vessel wall, therefore reducing inflammation and intimal thickening. While similar effects in humans need to be determined, O3FA dietary supplement shows promising results in the prevention of ICAS.

[Advances in studies on pharmacological action of main chemical constituent of Curcuma Zedoary in preventing in-stent restenosis].

Traditional Chinese medicine Curcuma Zedoary ( E'Zhu) contains essential oil, curcuminoid and other effective constituents, with such pharmacological actions as anti-platelet aggregation, lowing blood lipid, anti-oxidation and anti-inflammation. In recent years, studies have showed that certain extracts and chemical components of E'Zhu could mitigate myocardial cell mitochondria injury and protect vascular endothelium by enhancing heme oxygenase-1 activity, inhibit nuclear factor NF-kappaB, target genes interleukin-associated kinase-1 (IRAK-1), tumor necrosis factor receptor-6 (TRAF-6) and vascular cell adhesion molecule-1 (VCAM-1), reduce inflammatory infiltration, and inhibit growth factor-induced smooth muscle cells (SMCs) proliferation and migration by impacting oxidation of cellular phosphatases. Due to its different functions in vascular endothelial cells and smooth muscle cells, E'Zhu has been applied in drug-eluting stents, with a potential effect in preventing in-stent restenosis and thrombogenesis. In this paper, studies on pharmacological effects and mechanisms of extracts and main chemical constituents from E'Zhu in preventing vascular restenosis were summarized.

Is yoga training beneficial for exercise-induced bronchoconstriction?

BACKGROUND: Some studies have shown the beneficial effects of yoga for individuals with bronchial hyperreactivity with regard to (1) a reduction in the use of rescue medication, (2) an increase in exercise capacity, and (3) an improvement in lung function. Despite the fact that yoga is promising as a new treatment for pediatric patients, further studies are needed to assess the use of this training for asthma management. OBJECTIVE: This study was performed to assess the beneficial effects of yoga in exercise-induced bronchoconstriction (EIB) in children. DESIGN: The study was prospective, with no control group. Participants were randomly chosen among the new patients at the unit. SETTING: This study was conducted in the Erciyes University School of Medicine, Pediatric Allergy Unit, in Kayseri, Turkey. PARTICIPANTS: Two groups of asthmatic children aged 6-17 y were enrolled in the study: (1) children with positive responses to an exercise challenge (n = 10), and (2) those with negative responses (n = 10). INTERVENTION: Both groups attended 1-h sessions of yoga training 2 ×/wk for 3 mo. OUTCOME MEASURES: Researchers administered spirometric measurement to all children before and immediately after participating in an exercise challenge. This process was performed at baseline and at the study's end. Age, gender, IgE levels, eosinophil numbers, and spirometric measurement parameters including forced expiratory volume in 1 sec (FEV1), forced expiratory flow 25%-75% (FEF25%-75%), forced vital capacity (FVC), peak expiratory flow percentage (PEF%), and peak expiratory flow rate (PEFR) were compared using the Mann-Whitney U test and the Wilcoxon test. A P value < .05 was considered significant. RESULTS: At baseline, no significant differences were observed between the groups regarding demographics or pre-exercise spirometric measurements (P > .05, Mann-Whitney U test). Likewise, no significant differences in spirometric measurements existed between the groups regarding the change in responses to an exercise challenge after yoga training (P > .05, Wilcoxon test). For the exercise-response-positive group, the research team observed a significant improvement in maximum forced expiratory volume 1% (FEV1%) fall following the exercise challenge after yoga training (P > .05, Wilcoxon test). All exercise-response-positive asthmatics became exerciseresponse-negative asthmatics after yoga training. CONCLUSION: This study showed that training children in the practice of yoga had beneficial effects on EIB. It is the research team's opinion that yoga training can supplement drug therapy to achieve better control of asthma.

[Influence of acupuncture on cerebral hemodynamic reserve during the preoperative period in patients with associated brachiocephalic stenosis].

OBJECTIVE: To evaluate the possibility of acupuncture, as an element of preoperative preparation of the patient to carotid endarterectomy, for increasing the tolerance of patients with brachiocephalic stenosis to cerebral ischemia. MATERIAL AND METHODS: We studied 40 inpatients with low tolerance to carotid compression test. Ultrasound examination of brachiocephalic and intracranial blood flow was carried out, including carotid compression, apneic and hyperventilation tests. We examined 20 people from the control group before traditional medicinal treatment as well as after first and second therapeutic courses; 20 patients from the main group were tested before and after medicinal treatment, and after acupuncture course. RESULTS: We couldn't identify any significant changes in cerebral hemodynamic reserve in patients with severe carotid stenosis after medicinal therapy; at the same time we registered its reliable 2.16 fold growth after acupuncture treatment. CONCLUSION: Аcupuncture treatment leads to cerebral hemodynamic reserve growth in most patients with significant brachiocephalic stenosis. The inclusion of acupuncture in therapeutic complex improves the quality of preoperative preparation to carotid endarterectomy and its tolerability.

Antiplatelet and anticoagulant drugs for prevention of restenosis/reocclusion following peripheral endovascular treatment.

BACKGROUND: Peripheral arterial disease (PAD) is frequently treated by balloon angioplasty. Restenosis/reocclusion of the dilated segments occurs often, depending on length of occlusion, lower leg outflow, stage of disease and presence of cardiovascular risk factors. To prevent reocclusion, patients are treated with antithrombotic agents. This is an update of a review first published in 2005. OBJECTIVES: To determine whether any antithrombotic drug is more effective in preventing restenosis or reocclusion after peripheral endovascular treatment, compared to another antithrombotic drug, no treatment, placebo or other vasoactive drugs. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched 14 February 2012) and CENTRAL (2012, Issue 1). SELECTION CRITERIA: We selected randomised controlled trials (RCTs). Participants were patients with symptomatic PAD treated by endovascular revascularisation of the pelvic or femoropopliteal arteries. Interventions were anticoagulant, antiplatelet or other vasoactive drug therapy compared with no treatment, placebo or any other vasoactive drug. Clinical endpoints were reocclusion, restenosis, amputation, death, myocardial infarction, stroke, major bleeding and other side effects, such as minor bleeding, puncture site bleeding, gastrointestinal side effects and haematoma. DATA COLLECTION AND ANALYSIS: We independently extracted and assessed details of the number of randomised patients, treatment, study design, patient characteristics and risk of bias. Analysis was based on intention-to-treat data. To examine the effects of outcomes such as reocclusion, restenosis, amputation and major bleeding, we computed odds ratios (OR) with 95% confidence intervals (CI) using a fixed-effect model. MAIN RESULTS: Twenty-two trials with a total of 3529 patients are included (14 in the original review and a further eight in this update). For the majority of comparisons, only one trial was available so results were rarely combined in meta-analyses. Individual trials were generally small and risk of bias was often unclear due to limitations in reporting. Three trials reported on drug versus placebo/control; results were consistently available for a maximum follow-up of only six months. At six months post intervention, a statistically significant reduction in reocclusion was found for high-dose acetylsalicylic acid (ASA) combined with dipyridamole (DIP) (OR 0.40, 95% CI 0.19 to 0.84), but not for low-dose ASA combined with DIP (OR 0.69, 95% CI 0.44 to 1.10; P = 0.12) nor in major amputations for lipo-ecraprost (OR 0.89, 95% CI 0.44 to 1.80). The remaining trials compared different drugs; results were more consistently available for a longer period of 12 months. At 12 months post intervention, no statistically significant difference in reocclusion/restenosis was detected for any of the following comparisons: high-dose ASA versus low-dose ASA (OR 0.98, 95% CI 0.64 to 1.48; P = 0.91), ASA/DIP versus vitamin K antagonists (VKA) (OR 0.65, 95% CI 0.40 to 1.06; P = 0.08), clopidogrel and aspirin versus low molecular weight heparin (LMWH) plus warfarin (OR 0.31, 95% CI 0.06 to 1.68; P = 0.18), suloctidil versus VKA: reocclusion (OR 0.59, 95% CI 0.20 to 1.76; P = 0.34), restenosis (OR 1.87, 95% CI 0.66 to 5.31; P = 0.24) and ticlopidine versus VKA (OR 0.71, 95% CI 0.37 to 1.36; P = 0.30). Treatment with cilostazol resulted in statistically significantly fewer reocclusions than ticlopidine (OR 0.32, 95% CI 0.13 to 0.76; P = 0.01). Compared with aspirin alone, LMWH plus aspirin significantly decreased occlusion/restenosis (by up to 85%) in patients with critical limb ischaemia (OR 0.15, 95% CI 0.06 to 0.42; P = 0.0003) but not in patients with intermittent claudication (OR 1.73, 95% CI 0.97 to 3.08; P = 0.06) and batroxobin plus aspirin reduced restenosis in diabetic patients (OR 0.28, 95% CI 0.13 to 0.60). Data on bleeding and other potential gastrointestinal side effects were not consistently reported, although there was some evidence that high-dose ASA increased gastrointestinal side effects compared with low-dose ASA, that clopidogrel and aspirin resulted in fewer major bleeding episodes compared with LMWH plus warfarin, and that abciximab resulted in more severe bleeding episodes. AUTHORS' CONCLUSIONS: There is limited evidence suggesting that restenosis/reocclusion at six months following peripheral endovascular treatment is reduced by use of antiplatelet drugs compared with placebo/control, but associated information on bleeding and gastrointestinal side effects is lacking. There is also some evidence of variation in effect according to different drugs with cilostazol reducing reocclusion/restenosis at 12 months compared with ticlopidine and both LMWH and batroxobin combined with aspirin appearing beneficial compared with aspirin alone. However, available trials are generally small and of variable quality and side effects of drugs are not consistently addressed. Further good quality, large-scale RCTs, stratified by severity of disease, are required.

Effect of fish oil supplementation on graft patency and cardiovascular events among patients with new synthetic arteriovenous hemodialysis grafts: a randomized controlled trial.

CONTEXT: Synthetic arteriovenous grafts, an important option for hemodialysis vascular access, are prone to recurrent stenosis and thrombosis. Supplementation with fish oils has theoretical appeal for preventing these outcomes. OBJECTIVE: To determine the effect of fish oil on synthetic hemodialysis graft patency and cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS: The Fish Oil Inhibition of Stenosis in Hemodialysis Grafts (FISH) study, a randomized, double-blind, controlled clinical trial conducted at 15 North American dialysis centers from November 2003 through December 2010 and enrolling 201 adults with stage 5 chronic kidney disease (50% women, 63% white, 53% with diabetes), with follow-up for 12 months after graft creation. INTERVENTIONS: Participants were randomly allocated to receive fish oil capsules (four 1-g capsules/d) or matching placebo on day 7 after graft creation. MAIN OUTCOME MEASURE: Proportion of participants experiencing graft thrombosis or radiological or surgical intervention during 12 months' follow-up. RESULTS: The risk of the primary outcome did not differ between fish oil and placebo recipients (48/99 [48%] vs 60/97 [62%], respectively; relative risk, 0.78 [95% CI, 0.60 to 1.03; P = .06]). However, the rate of graft failure was lower in the fish oil group (3.43 vs 5.95 per 1000 access-days; incidence rate ratio [IRR], 0.58 [95% CI, 0.44 to 0.75; P < .001]). In the fish oil group, there were half as many thromboses (1.71 vs 3.41 per 1000 access-days; IRR, 0.50 [95% CI, 0.35 to 0.72; P < .001]); fewer corrective interventions (2.89 vs 4.92 per 1000 access-days; IRR, 0.59 [95% CI, 0.44 to 0.78; P < .001]); improved cardiovascular event-free survival (hazard ratio, 0.43 [95% CI, 0.19 to 0.96; P = .04]); and lower mean systolic blood pressure (-3.61 vs 4.49 mm Hg; difference, -8.10 [95% CI, -15.4 to -0.85]; P = .01). CONCLUSIONS: Among patients with new hemodialysis grafts, daily fish oil ingestion did not decrease the proportion of grafts with loss of native patency within 12 months. Although fish oil improved some relevant secondary outcomes such as graft patency, rates of thrombosis, and interventions, other potential benefits on cardiovascular events require confirmation in future studies. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN15838383.

Effectiveness of the antegrade colonic enema stopper at preventing stomal stenosis: long-term follow-up.

AIM OF THE STUDY: Stomal stenosis is the commonest complication of the antegrade colonic enema (ACE) procedure, reportedly occurring in 25-55% of patients. As such, a simple ACE stopper device (a small silicone plug sited in the ACE conduit between catheterisations) was designed to prevent stenosis. We performed a long-term follow-up study to determine the effectiveness of the stopper device. METHODS: A retrospective case note review was performed of all patients who successfully underwent a primary ACE procedure over an 8.5-year period (January 2002 to June 2010). The inclusion criteria were (i) a minimum of 6 months follow-up, (ii) simple appendicostomy, (iii) caecal/colonic flap. In all patients an ACE stopper was sited in the conduit for at least 4 months and removed only for catheterisation. Data are mean±SEM. MAIN RESULTS: 38 children were included in our study. Mean age at surgery was 9.6±0.5 years. Surgery was performed in 22 patients for incontinence and in 16 for chronic constipation. 31 underwent an appendicostomy and 7 had a caecal/colonic flap; all received an ACE stopper. The mean follow-up was 2.6±0.3 years. Only 3 patients (8%) developed stomal stenosis. The first occurred 6 months postoperatively, resulting from an ACE stopper which was too small and consequently persistently fell out. This conduit required dilatation. The second occurred at 27 months secondary to a stomal infection and required surgical revision. The third occurred 8 months postoperatively for no obvious cause, and was treated with dilation. 1 patient experienced stomal leakage. CONCLUSION: The ACE stopper is a simple yet highly effective method of preventing stomal stenosis. We recommend using the stopper in all ACE patients.

Dribbling diversion in Y-V glanuloplasty modified Mathieu repair.

INTRODUCTION: Aim of the study was to determine the impact of an indwelling transurethral catheter on surgical outcome and postoperative micturation in Y-V glanuloplasty modified Mathieu repair for primary hypospadias. MATERIALS AND METHODS: Fifty-nine consecutive boys underwent Y-V glanuloplasty modified Mathieu repair for primary distal hypospadias in our institution. The first 37 patients (group A) had catheterless repair. Due to significant painful postoperative urination, the next 22 children (group B) had an indwelling transurethral catheter (5 Fr feeding tube) for 24-48 hours. Adjunct caudal analgesia and penile block was given in both groups. Pain during postoperative voiding, urinary retention, meatal stenosis and fistula formation was statistically analysed with Wilcoxon's signed rank test. RESULTS: All patients in group A had distressing painful first micturation (p < 0.05). Eight children did not pass urine for more than 8 hours. Five (13.5 %) patients had urinary retention, 3 of whom required catheterisation (p < 0.05). Six (16 %) boys developed meatal stenosis and a further 5 (13.5 %) had urethrocutaneous fistula. In group B all patients had easy micturation after removal of the catheter. Only 1 boy developed a urethrocutaneous fistula and none of the boys in this group presented with meatal stenosis. CONCLUSION: An indwelling transurethral catheter obviates urinary retention and avoids distressing postoperative micturation. It minimises the chance of urethrocutaneous fistula and meatal stenosis in Y-V glanuloplasty modified Mathieu repair.

The use of an antegrade continence enema stopper in catheterizable channels virtually eliminates the incidence of stomal stenosis: preliminary experience.

PURPOSE: We report the effectiveness of an antegrade continence enema stopper device in preventing stomal stenosis in catheterizable channels. MATERIALS AND METHODS: All cases in which a channel was created for clean intermittent catheterization during a 5-year period beginning in May 2002 were included in the analysis. For the first 31 months the catheterizable channels were used for clean intermittent catheterization but were not kept patent between catheterizations (group 1, 19 patients). For the next 29 months we began to use an antegrade continence enema stopper in the stoma between catheterizations for a period of 3 to 6 months postoperatively (group 2, 14 patients). RESULTS: A total of 33 catheterizable channels were studied. Six catheterizable channels in group 1 (32%) had to be revised within 6 months of reconstruction. No catheterizable channel in group 2 had to be revised. This difference is statistically significant (p = 0.02). CONCLUSIONS: An antegrade continence enema stopper inserted into the catheterizable channel for 3 to 6 months postoperatively effectively eliminates the incidence of stomal stenosis.

Motor cortex stimulation in rats with chronic constriction injury.

Motor cortex stimulation (MCS) has gained a significant role in treatment of neuropathic pain. In order to evaluate effect of MCS in experimental animals we applied MCS to rats with neuropathic pain, which was evoked by chronic constriction injury (CCI) to the left sciatic nerve. Pain thresholds of both hind limbs were measured before, immediately after MCS, 1 h after MCS and 1 day after MCS. Effect of the stimulation was studied with respect to laterality (contralateral and ipsilateral MCS) and duration (short-term 10-min and long-term 1-h stimulation). It was found out that in control rats MCS did not affect thermal nociceptive thresholds. However, in CCI animals following results were obtained: difference score (difference in paw withdrawal latency between ligated and non-ligated hind limb) significantly decreased after both short- and long-term contralateral MCS; the difference score after the long-term ipsilateral MCS (related to the ligated hind limb) was not significantly different from that of intact animals; the effects of the contralateral short-term and the ipsilateral long-term stimulation faded within 1 h after the end of MCS, while the effect of the contralateral long-term MCS remained 1 h after the end of the MCS and faded within 24 h. It is concluded that MCS in experimental animals exerts similar effects as in human suffering from neuropathic pain and that the effect might be evoked from both cerebral cortices.

Antinociceptive activity of n-butanol fraction from MeOH extracts of Paederia scandens in mice.

The n-butanol fraction of the MeOH extract from Paederia scandens was evaluated for antinociceptive activity in mice using chemical and thermal models of nociception. The n-butanol fraction, given orally at doses of 150, 300 and 600 mg/kg produced significant inhibition of chemical nociception induced by intraperitoneal acetic acid and subplantar formalin or capsaicin injections, and of thermal nociception in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at a dose of 600 mg/kg. In the pentobarbital sodium-induced sleeping time test and the open-field test, the n-butanol fraction neither significantly enhanced pentobarbital sodium-induced sleeping time nor impaired motor performance, indicating that the observed anti-nociception was unlikely to be due to sedation or motor abnormality. Moreover, the n-butanol fraction-induced anti-nociception in both the capsaicin and formalin tests was insensitive to naloxone or glibenclamide but was significantly antagonized by nimodipine. These results suggest that the n-butanol fraction produced anti-nociception possibly related to nimodipine-sensitive L-type Ca2+ channels, which merits further studies regarding the precise site and mechanism of action. Furthermore, four iridoid glycosides isolated from the n-butanol fraction might be related to its antinociceptive action fraction. Therefore, the effect on analgesic activity of each chemical compound in large quantity might well be considered in a further study.

[Effects of Sini decoction on vascular stenosis after iliac artery balloon injury and oxidative stress in rabbits].

OBJECTIVE: To investigate the effect of Sini decoction (SND) in preventing vascular restenosis and protecting against oxidative stress after rabbit iliac artery balloon injury. METHODS: Twenty-four male New Zealand albino rabbits were equally randomized into control group, model group and SND group. Rabbits in the control group were fed with common forage, and those in the model and SND groups with high-fat diet. Two weeks later, the iliac arteries of the rabbits in the latter two groups were subjected to balloon injury. Four weeks after the operation, the rabbits were killed and the vascular structure was observed by scanning electron microscope and optical microscope, with the serum cholesterol level, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level determined. RESULTS: Scanning electron microscopy showed that the endothelial cell lining in the iliac artery of the control and SND group remain regular, but the arteries in the model group presented with desquamated and exposure of the collagen fibril beneath the endothelium. Optical microscope revealed narrowed vascular lumen, thicken intima and numerous arteriosclerotic plaques in the model group in comparison with the control group, whereas the vascular lumen and intima thickness remained basically normal in SND group. The levels of total cholesterol, low-density lipoprotein cholesterol and triglyceride were decreased with high-density lipoprotein cholesterol levels increased in SND group, which was not observed in the model group. The serum SOD activity was higher in the control group than in the model and SND groups, but SND group had higher serum SOD activity than the model group. The serum MDA level was lower in the control group than in the other two groups, but SND group had lower MDA level than the model group. CONCLUSION: SND can alleviate intimal hyperplasia and vascular stenosis in injured rabbit iliac artery, possibly in relation to increased SOD activity and decreased lipid peroxidation as a result of SND treatment.

Dissociation in the effect of nedocromil on mannitol-induced cough or bronchoconstriction in asthmatic subjects.

OBJECTIVE: Inhaled mannitol induces both bronchoconstriction and cough. Nedocromil sodium greatly attenuates mannitol-induced bronchoconstriction. Knowledge about the effect of nedocromil on mannitol-provoked cough might, therefore, clarify the mechanisms of this response. METHODOLOGY: Inhalation challenges with mannitol powder were performed after inhalation of 8 mg of nedocromil or its placebo in 24 subjects with asthma. The study was double-blind, randomised, and placebo-controlled. The mannitol-provoked coughs were manually recorded and the mannitol-induced bronchoconstriction was measured with a spirometer. RESULTS: The cumulative dose of mannitol that provoked at least two coughs tended to be higher on the nedocromil day than on the placebo day (34 (22--53) mg vs 26 (18--37) mg, P=0.051). The cumulative number of coughs per dose of mannitol was slightly, but significantly, lower on the nedocromil than on the placebo day (4.2 (2.8--6.3) coughs/100 mg vs 6.1 (4.0--9.4) coughs/100 mg, P=0.037). However, when analysed on a constant-dose basis, nedocromil provided no protection for coughing (-1% protection), whereas the protection for bronchoconstriction was clear (55% protection). CONCLUSIONS: Nedocromil strongly attenuates mannitol-induced bronchoconstriction but has a negligible effect on mannitol-provoked cough. Therefore, these responses seem to have different pathways in asthma. Recording of both provoked coughs and induced bronchoconstriction during mannitol challenge may provide supplementary information about a patient's disease.

Esculetin inhibits Ras-mediated cell proliferation and attenuates vascular restenosis following angioplasty in rats.

The proliferation of vascular smooth muscle cells (VSMCs) induced by injury to the intima of arteries is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis. Esculetin, derived from the Chinese herb Artemisia scoparia, is well known as a lipoxygenase inhibitor. We have investigated the inhibitory effects of esculetin on VSMC proliferation and intimal hyperplasia by balloon angioplasty in the rat. We determined, using [3H]thymidine incorporation and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, that esculetin inhibited the proliferation of VSMCs via a lipoxygenase-independent pathway. Three predominant signaling pathways were identified to be inhibited by esculetin: (a) the activation of p42/44 mitogen-activated protein kinase (MAPK) and the downstream effectors of c-fos and c-jun immediate early genes by means of western and reverse transcription-polymerase chain reaction (RT-PCR) analyses; (b) the activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), using the electrophoretic mobility shift assay; and (c) the activation of phosphoinositide 3-kinase (PI 3-kinase) and cell cycle progression, by western blot analysis and flow cytometric detection. Furthermore, esculetin also profoundly inhibited Ras activation, a shared upstream event of the above signaling cascades. In vascular injury studies, intraperitoneal administration of esculetin significantly suppressed intimal hyperplasia induced by balloon angioplasty. We conclude that esculetin blocks cell proliferation via the inhibition of an upstream effector of Ras and downstream events including p42/44 MAPK activation, PI 3-kinase activation, immediate early gene expression, as well as NF-kappaB and AP-1 activation. It also inhibits intimal hyperplasia after balloon vascular injury in the rat, indicating the therapeutic potential for treating restenosis after arterial injury.

Tetradecylthioacetic acid reduces stenosis development after balloon angioplasty injury of rabbit iliac arteries.

BACKGROUND: tetradecylthioacetic acid (TTA) is a synthetic long-chain fatty acid analogue that inhibits the oxidative modification of low-density lipoprotein particles in vitro. We examined the influence of TTA on the arterial wall response after balloon angioplasty injury in a rabbit iliac model. METHODS AND RESULTS: 14 rabbits were randomized to receiving either TTA fatty acids 800 mg daily perorally (weight 3.6+/-0.1 kg) or to normal diet (weight 3.5+/-0.5 kg, P=NS). Angioplasty was performed via right carotidotomy on both iliac arteries using an oversized balloon catheter, the TTA group being pretreated for 3 weeks. After angioplasty, the lumen diameter was 2.37+/-0.18 versus 2.36+/-0.13 mm for the TTA and control groups, respectively (P=NS). At 10 weeks follow-up angiography, minimal luminal diameter was 1.64+/-0.27 versus 1.13+/-0.52 mm for the TTA and control groups respectively (P<0.05). Histomorphometry did not show significant differences in intimal hyperplasia between the two groups (maximal intimal thickness 0.22+/-0.04 versus 0.19+/-0.10 mm, P=NS and intimal area 0.32+/-0.12 versus 0.36+/-0.23 mm(2), P=NS for the TTA and the control groups, respectively). In the heart, the sum of the n-3 fatty acids was 8.9+/-2.7 in the TTA group versus 4.3+/-0.2 mol% in the control group (P<0.05). The anti-inflammatory fatty acid index, calculated as (22:5 n-3+22:6 n-3+20:3 n-6)/20:4 n-6, was 0.76+/-0.10 vs. 0.25+/-0.03 for the TTA and control groups, respectively (P<0.05). In vitro TTA (100 microM) reduced the proliferation of human smooth muscle cell by more than 50%. CONCLUSION: treatment with TTA is associated with positive arterial remodeling after angioplasty injury. The significance of the in vitro inhibition of human smooth muscle cell proliferation needs to be further elucidated.