Background
Increased prevalence of functional gastrointestinal disorders in women and perimenstrually accentuated symptoms imply that sexual hormones play a crucial role in the pathogenesis of such ...syndromes. The aim of this study was to analyze the selective effect of estrogen on visceral sensitivity in gonadectomized female and male Lewis rats with or without prior treatment with butyrate enemas.
Methods
Following ovariectomy (OVX) or orchiectomy (ORX) estradiol pellets (E2‐P) or sham pellets (Sham‐P) were implanted. After treatment with butyrate (BUT) or saline (NaCl) enemas, colorectal distensions (CRD) were performed and the visceromotor reflex (VMR) to CRD was measured by electromyography.
Key Results
Gender did not influence VMR to CRD in gonadectomized animals. VMR in E2‐P animals compared to Sham‐P animals was increased (635 ± 32 μVs vs 470 ± 39 μVs; p = 0.002). Overall, instillation of butyrate enemas did not influence VMR to CRD. A comparison of CRD clusters showed that butyrate enemas in the E2‐P animals resulted in a significant sensitization in both OVX and ORX animals. In female rats, sensitization was also caused by estrogen substitution alone.
Conclusion & Inferences
In our animal model, estrogen is a strong factor for an increase in visceral sensory function. Surprisingly, the treatment with butyrate alone did not evoke a general rise in VMR to CRD. Rats treated with butyrate enemas and under selective estrogen substitution developed visceral sensitization during the series of CRDs.
To study the effect of sexual hormones on visceral nociception, the selective effect of estrogen on visceral sensitivity in gonadectomized female and male Lewis rats with or without prior treatment with butyrate enemas was studied. In our rat model, estrogen is a strong factor for an increase in visceral sensory function.
Strictures are a frequent complication of eosinophilic esophagitis. The efficacy and safety of topical corticosteroids and of dilation of eosinophilic esophagitis-associated strictures have not yet ...been thoroughly clarified. We present a retrospective analysis of 10 adult patients with eosinophilic esophagitis who had symptomatic esophageal stenosis that was unresponsive to topical corticosteroids, and who were treated using bougienage. Eight patients had one single stricture, one patient had two, and another had three strictures; mean stricture length was 2.1 cm (range 1 - 6 cm). Bougienage led to prompt symptom relief. Apart from transient postprocedural odynophagia, no severe complications occurred. During the follow-up (mean 6 months; range 2 - 11 months), all patients enjoyed sustained treatment response.
Acute gastrointestinal infections with transient mucosal inflammation frequently precede the onset of functional GI disorders with altered visceral sensory function. We hypothesized that an acute ...inflammation of the mucosa is linked to long-lasting alterations of afferent visceral pathways. Utilizing abdominal wall electromyography, we tested the visceromotor response to tonic rectal distension (60 mm Hg/3 min) in fasted, conscious, male Lewis rats (n = 40) with a barostat device before and 2, 4, 15, and 17 weeks after rectal instillation of saline or trinitrobenzenesulfonic acid plus ethanol. Tissue samples from paired controls were obtained to assess histologic tissue alterations. Inflammatory changes were present up to 2 weeks after acid/ethanol instillation but not after saline instillation. Compared to baseline measurements, the visceromotor response to colorectal distension increased significantly and reached a maximum 17 weeks (P < 0.001) after induction of colitis, while it decreased in control experiments (P < 0.05). In conclusion, these data suggest that an acute inflammation has long-term effects on somatosensory functioning.
The optimal clinical management of patients following ingestion of potentially caustic lesions is still undetermined. In particular, the indication for early upper GI endoscopy in this context ...remains unclear.
To draft recommendations regarding the use of early upper GI endoscopy following hospital admissions of patients after ingestion of potentially caustic agents.
For this purpose, a retrospective cohort study of patients treated for ingestion of potentially caustic substances during a 13 year-period at the university hospital of Berne was performed.
In total, 61 patients with acute ingestion of potentially caustic substances were identified. Overall mortality was 5 %. 11/61 patients had to be admitted to the intensive care unit. Most ingestions were performed in suicidal intention (62 %). In 53 % of these patients, a combined ingestion of several substances occurred. In 33 % of patients, an early upper GI endoscopy was performed within 24 hours after ingestion. The degree of burn depended upon the hazard potential of the respective substance. In patients with ingestion of low risk substances, upper GI endoscopy was only performed when additional risk factors were present.
Based upon the results of the present study, ingestion of potentially caustic agents requires an individualized strategy whether or not to perform early endoscopy.
Abstract Synaptic vesicles can undergo several modes of exocytosis, endocytosis, and trafficking within individual synapses, and their fates may be linked to different vesicular protein compositions. ...Here, we mapped the intrasynaptic distribution of the synaptic vesicle proteins SV2B and SV2A in glutamatergic synapses of the hippocampus using three-dimensional electron microscopy. SV2B was almost completely absent from docked vesicles and a distinct cluster of vesicles found near the active zone. In contrast, SV2A was found in all domains of the synapse and was slightly enriched near the active zone. SV2B and SV2A were found on the membrane in the peri-active zone, suggesting the recycling from both clusters of vesicles. SV2B knockout mice displayed an increased seizure induction threshold only in a model employing high-frequency stimulation. Our data show that glutamatergic synapses generate molecularly distinct populations of synaptic vesicles and are able to maintain them at steep spatial gradients. The almost complete absence of SV2B from vesicles at the active zone of wildtype mice may explain why SV2A has been found more important for vesicle release.
The reference surveillance method in patients with Barrett's esophagus is careful endoscopic observation, with targeted as well as random four-quadrant biopsies. Autofluorescence endoscopy (AFE) may ...make it easier to locate neoplasia. The aim of this study was to elucidate the diagnostic accuracy of surveillance with AFE-guided plus four-quadrant biopsies in comparison with the conventional approach.
A total of 187 of 200 consecutive Barrett's esophagus patients who were initially enrolled (73 % male, mean age 67 years, mean Barrett's segment length 4.6 cm), who underwent endoscopy for Barrett's esophagus in four study centers, were randomly assigned to undergo either AFE-targeted biopsy followed by four-quadrant biopsies or conventional endoscopic surveillance, also including four-quadrant biopsies (study phase 1). After exclusion of patients with early cancer or high-grade dysplasia, who underwent endoscopic or surgical treatment, as well as those who declined to participate in phase 2 of the study, 130 patients remained. These patients were examined again with the alternative method after a mean of 10 weeks, using the same methods described. The main study parameter was the detection of early cancer/adenocarcinoma or high-grade dysplasia (HGD), comparing both approaches in study phase 1; the secondary study aim in phase 2 was to assess the additional value of the AFE-guided approach after conventional surveillance, and vice versa. Test accuracy measures were derived from study phase 1.
In study phase 1, the AFE and conventional approaches yielded adenocarcinoma/HGD rates of 12 % and 5.3 %, respectively, on a per-patient basis. With AFE, four previously unrecognized adenocarcinoma/HGD lesions were identified (4.3 % of the patients); with the conventional approach, one new lesion (1.1 %) was identified. Of the 19 adenocarcinoma/HGD lesions detected during AFE endoscopy in study phase 1, eight were visualized, while 11 were only detected using untargeted four-quadrant biopsies (sensitivity 42 %). Of the 766 biopsies classified at histology as being nonneoplastic, 58 appeared suspicious (specificity 92 %, positive predictive value 12 %, negative predictive value 98.5 %). In study phase 2, AFE detected two further lesions in addition to the initial alternative approach in 3.2 % of cases, in comparison with one lesion with conventional endoscopy (1.7 %).
In this referral Barrett's esophagus population with a higher prevalence of neoplastic lesions, the AFE-guided approach improved the diagnostic yield for neoplasia in comparison with the conventional approach using four-quadrant biopsies. However, AFE alone was not suitable for replacing the standard four-quadrant biopsy protocol.
SUMMARY
Aim : To compare the efficacy of simethicone with placebo and the prokinetic cisapride in patients with functional dyspepsia.
Methods : One hundred and eighty‐five patients with functional ...dyspepsia were randomized and treated in a double‐dummy technique with simethicone (105 mg t.d.s.), cisapride (10 mg t.d.s.) or placebo (t.d.s.). The primary outcome measure was the O'Brien global measure of the patients' rating of 10 upper gastrointestinal symptoms (graded as absent=0, moderate=1, severe=2 or very severe=3). Outcome measures were assessed at baseline and after 2, 4 and 8 weeks of treatment (intention‐to‐treat).
Results : At 2, 4 and 8 weeks, treatment with simethicone and cisapride yielded significantly (all P values < 0.0001) better improvement of symptoms compared to placebo. Simethicone was significantly better than cisapride after 2 weeks (P=0.0007), but the differences were not statistically significant after 4 and 8 weeks. Patients treated with simethicone judged the efficacy of their treatment as very good in 46% of cases, compared to 15% and 16% receiving cisapride and placebo, respectively.
Conclusions : Simethicone and cisapride were significantly better than placebo for symptom control in patients with functional dyspepsia after 2, 4 and 8 weeks of treatment. Simethicone was also superior to the prokinetic cisapride in the first 2 weeks of treatment.
Background The high prevalence of functional bowel disorders among the general population contrasts with the limited number of pharmacological treatment options for this condition. This has led to ...an interest for alternative therapeutic approaches. Padma® Lax is an herbal laxative on the basis of Tibetan formulas. Our aim is to examine the effect of Padma Lax (A) on visceral nociception in vivo and (B) on contractile activity of longitudinal smooth muscle of the lower gut in vitro and ex vivo.
Methods (A) Visceral sensory function in response to colorectal distension was assessed by abdominal wall electromyography in male Wistar rats pretreated with Padma Lax. (B) Effects of Padma Lax on contractility of gut smooth muscles were studied both in vitro with superfusion of the agent and ex vivo following oral administration of the preparation. Activities were measured as area under the curve.
Key Results (A) For visceral sensitivity, no differences were observed between the Padma Lax and the control group. (B) Proximal colon muscle strips of the Padma Lax pretreated group showed significantly lower spontaneous contractility ex vivo than controls. Cholinergic procontractile stimulation was reduced in Padma Lax pretreated group and in colon strips of naive rats when Padma Lax was superfused in vitro (all P < 0.05).
Conclusion & Inferences Cholinergic mechanisms appear to be important in the modulation of rat proximal colon contractility of orally and directly applied Padma Lax. These findings help elucidate a potential mechanism of action of this herbal remedy which has undergone clinical testing in patients with constipation predominant irritable bowel syndrome.
In a number of different experimental paradigms of somatic pain, there is evidence for a vagally mediated antinociceptive system. This pathway probably involves opioid mechanisms. However, whether ...this pathway is activated in visceral pain or if it involves subdiaphragmatic vagal afferents is unclear. The aim of the present study was to determine whether subdiaphragmatic vagal afferents mediate antinociception in response to a visceral stimulus and whether this involves an opioid pathway. Colorectal distension was performed in fasted, conscious male Sprague–Dawley rats using a balloon catheter connected to an electronic distension device. The number of abdominal contractions (visceromotor response) in response to a tonic colorectal distension (60 mmHg for 10 min) was recorded. Experiments were performed in sham or subdiaphragmatically vagotomized, perineural vehicle‐ or capsaicin‐treated rats (to functionally denervate vagal afferents) before and after administration of naloxone (25 mg kg−1bodyweight intraperitoneally). Vagotomy, capsaicin and naloxone pretreatments all significantly enhanced the visceromotor response to colorectal distension. The effect of naloxone in capsaicin‐treated rats did not appear to be additive. These results suggest that activation of subdiaphragmatic afferents, which can be blocked by capsaicin, may play a role in opioid‐dependent antinociceptive pathways activated by a noxious visceral stimulus.
The current recommendations on indications, technical performance, and interpretation of diagnostic techniques for oesophageal reflux update the German recommandations about 24 hour pH measurement of ...2003. The recommendations encompass conventional pH measurement, wireless pH measurement, pH and impedance measurements, and bilirubin measurement (duodenogastro-oesophageal reflux).
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