P2X3 receptor-mediated visceral hyperalgesia and neuronal sensitization following exposure to PTSD-like stress in the dorsal root ganglia of rats.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) often share co-morbidity with chronic pain conditions. Recent studies suggest a role of P2X3 receptors and ATP signaling in pain conditions. However, the underlying mechanisms of visceral hyperalgesia following exposure to PTSD-like stress conditions remain unclarified. METHODS: The behavior and hormones relevant for PTSD were studied. Visceromotor responses (VMR) and the abdominal withdrawal reflexes (AWR) to colorectal distention (CRD) were recorded to determine P2X3-receptor-mediated alteration of hyperalgesia following single-prolonged stress (SPS) exposure. Immunofluorescence, Western blotting, and patch-clamp were used. KEY RESULTS: The escape latency, adrenocorticotropic hormone and cortisol were increased on days 7-14. Visceromotor responses and AWR was reduced at day 1 in SPS rats but increased to higher levels than in controls after exposure to day 7. Intrathecal administration of the P2X3-receptor antagonist TNP-ATP abolished the CRD response. Based on immunofluorescence and Western blotting analysis, SPS-treated rats exhibited reduced P2X3 expression in dorsal root ganglia (DRG) after day 1 compared with controls. P2X3 expression in DRG was enhanced on day 7 after SPS and the increase of the P2X3 expression was maintained on day 14 and 21 compared with controls. The P2X3-receptor agonist α,ß-me ATP (10 µM) induced a fast desensitizing inward current in DRG neurons of both control and SPS-treated rats. The average peak current densities in SPS-treated group were increased 3.6-fold. TNP-ATP (100 nM) markedly blocked all fast α,ß-me ATP-induced inward currents in the DRG neurons both in control and SPS-treated rats. CONCLUSIONS & INFERENCES: The data indicate an important role of P2X3 signaling in visceral hyperalgesia following PTSD-like stress.

Inhibition of p38 MAPK activation attenuates esophageal mucosal damage in a chronic model of reflux esophagitis.

BACKGROUND: Reflux esophagitis (RE) is one of the common gastrointestinal diseases that are increasingly recognized as a significant health problem. This study was designed to investigate the role of p38 mitogen-activated protein kinase (MAPK) in experimental chronic RE model of rats. METHODS: Chronic acid RE rats were induced by fundus ligation and partial obstruction of the pylorus and treated with SB203580 (a p38 MAPK inhibitor, i.p., 1 mg/kg/day) for 14 days. KEY RESULTS: Immunohistochemical staining and Western blotting results revealed the activation of p38 MAPK signaling in the esophagus mucosa 14 days post injury. Through gross and histological assessment, we found that inhibition of p38 MAPK activation by SB203580 attenuated esophageal mucosal damage in RE rats. Inhibition of p38 MAPK activation in RE rats attenuated esophageal barrier dysfunction, through enhancing the expression of tight junction proteins and reducing the expression of matrix matalloproteinases-3 and -9. Inhibition of p38 MAPK activation in RE rats reduced CD68-positive cells in esophagus mucosa and mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß in esophagus and protein levels of TNF-α, IL-6, and IL-1ß in serum. In addition, we found that inhibition of p38 MAPK activation in RE rats suppressed protein expression of inducible nitric oxide synthase and reduced formation of nitric oxide (NO), 3-nitrotyrosin, and malondialdehyde in esophagus. CONCLUSIONS & INFERENCES: Inhibition of p38 MAPK activation attenuated esophageal mucosal damage in acid RE rats, possibly by modulating esophageal barrier function and regulating inflammatory cell recruitment, and the subsequent formation of cytokines, NO, and reactive oxygen species.

Efficacy and safety of endoscopic biliary lithotripsy using FREDDY laser with a radiopaque mark under fluoroscopic guidance.

To date no clinic trials have reported on the safety and effectiveness of the use of a frequency-doubled double pulse neodymium YAG (FREDDY) laser with a radiopaque mark under fluoroscopic guidance to treat bile duct stones that are untreatable by conventional endoscopic therapy. We report the cases of 30 patients with impacted or large common bile duct (CBD) stones (> 1.5 cm) treated by endoscopic lithotripsy using FREDDY laser with a radiopaque mark under fluoroscopic guidance. During the procedure, the tip of the laser fiber was packaged with a radiopaque ring mark that was detectable by fluoroscopy. In these patients, complete bile duct clearance was achieved in 27 of the 30 patients (90 %). The majority of patients (18/30) were treated in a single session; the mean number of sessions needed to clear the bile ducts completely was 1.4 ± 0.6. Adverse events were noted in two patients, who both developed acute mild pancreatitis.

Epidemiology of functional constipation and comparison with constipation-predominant irritable bowel syndrome: the Systematic Investigation of Gastrointestinal Diseases in China (SILC).

BACKGROUND: The epidemiology and effects of functional constipation (FC) on Chinese people remain unclear. AIM: To investigate the epidemiology of FC and its distinction from constipation-predominant irritable bowel syndrome (IBS-C) in China. METHODS: A cross-sectional survey was conducted in a representative adult Chinese population (n = 16,078), which was selected from five regions using randomised, stratified, multistage sampling methodology. All respondents completed the modified Rome II questionnaire; 20% were asked to complete the 36-item Short Form (SF-36) and the Epworth Sleepiness Scale (ESS). RESULTS: Overall, 948 respondents (6%) had FC and FC was more prevalent in women than in men (8% vs. 4%, P < 0.001). Straining and hard stools were the two most frequent symptoms. FC was associated significantly with dyspepsia and abdominal bloating. All SF-36 domain scores were lower for respondents with FC than for those without. The prevalence of clinically meaningful daytime sleepiness was significantly higher in respondents with FC than in those without (22% vs. 14%, P = 0.003). Respondents with FC were more likely to strain, but less likely to have a feeling of incomplete emptying after a bowel movement than those with IBS-C. Respondents with IBS-C experienced similar demographics, quality of life and daytime sleepiness to those with FC. CONCLUSIONS: The prevalence of FC in China is substantially lower than that in Western countries. FC has negative effects on quality of life and daytime sleepiness. The demographics and burden of illness are similar between FC and IBS-C, although the clinical symptoms are somewhat different.

Diagnostic accuracy of features predicting lower gastrointestinal malignancy: a colonoscopy database review of 10,603 Chinese patients.

AIM: The diagnostic accuracy of colonoscopic features in predicting colorectal cancer (CRC) malignancy was studied. METHOD: Consecutive patients who underwent first-time colonoscopy for lower gastrointestinal (GI) symptoms from 1998 to 2009 were identified. Gender, age, symptoms, endoscopic and pathologic findings were reviewed. RESULTS: There were 10,603 patients. The overall prevalence of malignancy was 3.0% (313). Among these, only 58% (181/313) had features indicative of tumour formation. The overall sensitivity and specificity was 9.6% and 94.1%, respectively. The overall positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 2.66, 0.96 and 2.77, respectively. CONCLUSION: A large proportion of Chinese patients with CRC presented without features indicative of tumour formation.

Glyceryl trinitrate for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography: a meta-analysis of randomized, double-blind, placebo-controlled trials.

BACKGROUND AND STUDY AIMS: Although trials evaluating the preventive effect of glyceryl trinitrate (GTN; nitroglycerin) on pancreatitis occurring after endoscopic retrograde cholangiopancreatography (ERCP) have been reported, there is no agreement as to whether prophylactic GTN treatment can in fact reduce the incidence of post-ERCP pancreatitis. We performed a meta-analysis to compare the effects of prophylactic GTN with placebo on post-ERCP pancreatitis. STUDY DESIGN: Databases including PubMed, EMBASE, the Cochrane Library, and the Science Citation Index were searched to find relevant randomized controlled trials (RCTs). Two reviewers independently identified relevant trials evaluating the prophylactic effect of GTN on the occurrence of post-ERCP pancreatitis. The outcome measure was the incidence of post-ERCP pancreatitis. RESULTS: Eight trials involving 1920 patients were analyzed. Meta-analysis showed that the incidence of post-ERCP pancreatitis was significantly reduced by GTN treatment (GTN group 5.9 %, placebo group 9.8 %, P = 0.002), with a relative risk of 0.61 (95 % confidence interval 0.44 - 0.84). Patients who received GTN were 39 % less likely to develop pancreatitis. Subgroup analyses suggested that GTN administered by the sublingual or transdermal route may be useful. CONCLUSIONS: Prophylactic GTN is useful for prevention of post-ERCP pancreatitis, but the optimal dosage and the optimal route and timing of administration need further clarification before this treatment can come into routine clinical use.

Characterization of cortical potentials evoked by oesophageal balloon distention and acid perfusion in patients with functional heartburn.

Oesophageal visceral hypersensitivity is thought to be important in generating symptoms in functional heartburn (FH). However, the neurophysiological mechanisms involved are poorly understood. The aim of this study was to compare the characteristics of oesophageal cortical evoked potentials (CEPs) induced by balloon distension and acid perfusion in FH and controls. We studied 21 FH patients and 12 healthy volunteers. Oesophageal mechanical stimulation was performed using the specially constructed mechanical pump. CEPs were recorded using the 10-20 international system of electroencephalogram recording. Oesophageal distention elicited recognizable, reproducible and muti-peak CEPs. CEP latencies for N1, P1 and N2 components were significantly shorter (P = 0.016, P = 0.003 and P = 0.031, respectively) in FH than in controls before perfusion. Acid perfusion significantly decreased the latencies of N1, P1 and N2 (P = 0.022, P = 0.007 and P = 0.041, respectively) and significantly increased the amplitude of P1-N2 components (P = 0.020) in FH patients, but not in controls. In conclusion, cortical evoked potential responses evoked by oesophageal distention and acid perfusion were greater in FH than in controls, suggesting that dysfunction of visceral neural pathways and/or alterations in cortical processing may produce and mediate oesophageal hypersensitivity in FH. These findings provide the evidence that central sensitization contributes to the development and maintenance of oesophageal hypersensitivity.

[Adult spondylolisthesis treated with the combination of angled and pushing-pulling pedicle screws].

Altogether 28 patients with degenerative (22 cases), isthmic (4 cases), and post-traumatic (2 cases) spondylolisthesis were treated with a reduction fixation system using both angled and pushing-pulling pedicle screws. Preoperatively, the percentages of the sliprage were < or = 25% in 15 cases, < or = 50% in 11, and < or = 75% in 2 cases. All patients had low-back pain and/or leg pain. Postoperatively, 28 cases obtained a nearly anatomical reduction. The average rate of correction was 98%. There is a significant difference (P < 0.01) compared with preoperation. After reduction, all patients had only two segmental rigid fixations with posterolateral bone grafting or postero-inter-body fusion. 27 cases had satisfactory pain relief postoperatively. No patient deteriorated neurologically with surgery. All patients were followed up for a minimum of 8 months ranging from 8 to 28 months (average 19). At the end of follow-up, in 26 patients correction remained unchanged with X-ray demonstrating radiographic evidence of fusion. Neither pseudarthroses nor significant complications occurred. The new system is a safe and effective pedicular fixation system, it has a three-dimensional correction force that allows for reduction of the spondilolisthesis and fixation of only two segments. It also gives more rigid fixation to maintain the reduction and increase the fusion rate. The new system gives satisfactory results over conventional hook and sub-lamina wire and other segmental spinal pedicle screw instrumentation systems.

[Treatment of unstable fractures of thoracolumbar spine with neurologic injury using a reduction fixation spinal pedicle screws system].

Twenty-six patients with unstable burst fractures, chance fractures and fractures dislocations of the lower thoracic and lumbar spine were treated with a spinal pedical screw reduction fixation system (RF system). This system is a new device designed by Chinese scientists. In biomechanical testing, it provided three-dimensional reduction forces. The special design of angle pedicle screw provided accurate angle to restore the normal thoracic lumbar lordosis and to maintain it. The three-column spine in a lordotic position maximized the reduction and indirectly achieved a neurologic decompression in the spinal canal. All patients had an anatomical reduction by RF system except one case operated two weeks after injury, the spinal canal area increased over 30% by CT (P < 0.01). Except four cases with Frankle A out of twenty patients with neurologic deficits, all other patients had at least one grade progress. Of them one improved from A to D, ten from C and D to normal. These twenty patients were followed-up over six months. All of them maintained anatomical reduction by RF system. Bone grafting had successful fusion by follow-up X-ray examinations. There were no important complications after surgery. The system is of simple structure facilitation implantation and enable the patients beginning ambulatory movements early, therefore it gives more satisfactory results over conventional Harrington and other segmental spinal instrumentation systems.

[Anatomical restoration of thoracolumbar spine with burst fracture].

A burst fracture was created in the L1 vertebra of six fresh human cadaver spines and reduction was performed using AO fixator intern, reduction fixation (RF) device, and Steffee plate instrumentation systems to determine the reduction force (distraction vs distraction plus lordosis) contributing to the anatomical restoration of thoracolumbar spine. These three pedicular screw devices were applied to the specimens following the use of standard clinical technique for each device. The AO fixator intern and the RF device provided independent control of distraction and lordosis correction. The Steffee device maintained a set distraction and lordosis. The RF device provided pre-set fixed incremental lordosis, while the AO provided variable angular correction. Plain X-rays and CT scans were taken of the specimens before and after creation of the fracture and following application of each device. Results demonstrated that the symmetric lordotic distraction of the disc space and vertebral body provided by the RF device achieved the best possible reduction of the intracanal fragment and sagittal alignment.