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1.
Tech Coloproctol ; 26(1): 35-44, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34705136

ABSTRACT

BACKGROUND: Randomized controlled trials (RCTs) have reported that water exchange (WE) produced the highest adenoma detection rate (ADR) but did not evaluate right colon adenoma detection rate (rADR) as a primary outcome and only one of the trials employed blinded colonoscopists. The aim of our study was to determine whether, compared with air insufflation, WE significantly increases rADR and right colon serrated lesion detection rate (rSLDR) and decreases adenoma miss rate (rAMR). METHODS: This prospective, double-blind RCT was conducted at a regional hospital in Taiwan between December 2015 and February 2020. Standard WE and air insufflation were performed. After cecal intubation, the second blinded endoscopist examined the right colon and obtained rADR (primary outcome) and rSLDR. Then, the primary colonoscopist reinserted the scope to the cecum with WE in both groups and performed a tandem examination of the right colon to obtain rAMR. RESULTS: There were 284 patients (50.9% male, mean age 58.9 ± 9.4 years) who were randomized to WE (n = 144) or air insufflation (n = 140). The baseline characteristics were similar. The rADR (34.7% vs. 22.3%, p = 0.025), Boston Bowel Preparation Scale scores (mean, 2.6 ± 0.6vs. 2.2 ± 0.6, p < 0.001), rSLDR (18.1% vs. 7.1%, p = 0.007), and rAMR (31.5% vs. 45.2%, p = 0.038) were significantly different between WE and air insufflation. CONCLUSIONS: The current study demonstrated a significantly higher rADR and rSLDR with the WE method performed by blinded colonoscopists. The impact of the significant findings in this report on the occurrence of interval cancers deserves to be studied.


Subject(s)
Adenoma , Insufflation , Adenoma/diagnosis , Aged , Air , Colon , Colonoscopy , Female , Humans , Male , Middle Aged , Water
2.
United European Gastroenterol J ; 7(4): 477-487, 2019 05.
Article in English | MEDLINE | ID: mdl-31065365

ABSTRACT

Background: A low adenoma detection rate (ADR) increases risks of interval cancers (ICs). Proximal colon flat polyps, e.g. serrated lesions (SLs), are difficult to find. Missed proximal colon flat lesions likely contribute to IC. Aims: We compared chromoendoscopy with water exchange (CWE), water exchange (WE) and air insufflation (AI) in detecting adenomas in screening colonoscopy. Methods: After split-dose preparation, 480 veterans were randomized to AI, WE and CWE. Results: Primary outcome of proximal ADR (55.6% vs 53.4% vs 52.2%, respectively) were similar in all groups. Adenoma per colonoscopy (APC) and adenoma per positive colonoscopy (APPC) were comparable. Detection rate of proximal colon SLs was significantly higher for CWE and WE than AI (26.3%, 23.6% and 11.3%, respectively, p = 0.002). Limitations: single operator; SLs only surrogate markers of but not IC. Conclusions: When an endoscopist achieves high-quality AI examinations with overall ADR twice (61.6%) the recommended standard (30%), use of WE and CWE does not produce further improvement in proximal or overall ADR. Comparable APC and APPC confirm equivalent withdrawal inspection techniques. WE alone is sufficient to significantly improve detection of proximal SLs. The impact of increased detection of proximal SLs by WE on prevention of IC deserves to be studied. This study is registered at ClinicalTrial.gov (NCT#01607255).


Subject(s)
Adenoma/diagnostic imaging , Colonoscopy/methods , Colorectal Neoplasms/diagnostic imaging , Early Detection of Cancer/methods , Mass Screening/methods , Adenoma/pathology , Aged , Air , Colon/diagnostic imaging , Colon/pathology , Colorectal Neoplasms/pathology , Coloring Agents/administration & dosage , Female , Humans , Indigo Carmine/administration & dosage , Insufflation/methods , Intestinal Mucosa/diagnostic imaging , Intestinal Mucosa/pathology , Male , Middle Aged , Prospective Studies , United States , United States Department of Veterans Affairs , Water/administration & dosage
3.
Surg Endosc ; 33(7): 2267-2273, 2019 07.
Article in English | MEDLINE | ID: mdl-30334167

ABSTRACT

BACKGROUND: Underwater polypectomy (UWP) of large (≥ 20 mm) colorectal lesions is well described, but reports of UWP for lesions ≤ 20 mm in size, which account for > 95% of polyps encountered in routine clinical practice, are limited. We assessed the feasibility of UWP in routine practice across various sites for colorectal lesions ≤ 20 mm in size. METHODS: A multicenter retrospective study was performed on pooled data from nine colonoscopists at 3 U.S., 1 Taiwanese and 2 Italian sites. Outcomes related to UWP on lesions ≤ 20 mm in size were analyzed. RESULTS: In 117 patients, UWP netted 169 lesions. Polypectomy by hot (HSP, 54%) or cold (CSP, 41%) snare, and cold forceps (CFP, 5%) were performed successfully without endoscopic evidence of residual neoplasia or immediate clinically significant adverse events. The majority (74.6%) were tubular adenomas; 60.9% were from the proximal colon. Histopathologic margins were positive in 4 and unavailable in 26 CSP and 24 HSP specimens. The remainder had negative resection margins on pathologic reports. CONCLUSION: UWP for colorectal lesions ≤ 20 mm in routine practice across multiple sites confirms the feasibility and acceptability of this technique. Improvement of resection outcomes by UWP in routine practice deserves further evaluation in a randomized controlled trial.


Subject(s)
Colonic Polyps/surgery , Colonoscopy/methods , Colorectal Neoplasms/surgery , Adenoma/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Neoplasm, Residual/surgery , Retrospective Studies
4.
Endoscopy ; 43(9): 816-21, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21611947

ABSTRACT

Failure of cecal intubation when using air insufflation during scheduled unsedated colonoscopy in veterans prompted a literature search for a less uncomfortable approach. Water-related maneuvers as "adjuncts" to air insufflation were identified as effective in minimizing discomfort, although medication requirement was not reduced and willingness to repeat unsedated colonoscopy was not addressed. These adjunct maneuvers were combined with turning the air pump off to avoid colon elongation during insertion. Warm water infusion in lieu of air insufflation was evaluated in observational studies. Subsequent refinements evolved into the water method - a combination of air exclusion by aspiration of residual air to minimize angulations at flexures and a dynamic process of water exchange to remove feces in order to clear the view and aid insertion. In subsequent randomized controlled trials, the water method significantly reduced medication requirement, increased the proportion of patients in whom complete unsedated colonoscopy could be achieved, reduced patient recovery time burdens (sedation on demand), decreased abdominal discomfort during and after colonoscopy, enhanced cecal intubation, and increased willingness to repeat the procedure (scheduled unsedated). Supervised education of trainees and self-learning by an experienced colonoscopist were feasible. Lessons learned in developing the water method for optimizing patient-centered outcomes are presented. These proof-of-principle observations merit further research assessment in diverse settings.


Subject(s)
Colonoscopy/methods , Conscious Sedation , Insufflation/methods , Water/administration & dosage , Cecum , Female , Humans , Male , Patient Satisfaction
5.
Endoscopy ; 42(7): 557-63, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20593332

ABSTRACT

BACKGROUND AND STUDY AIMS: Water immersion is an alternative colonoscopy technique that may reduce discomfort and facilitate insertion of the instrument. This was a prospective study to compare the success of colonoscopy with minimal sedation using water immersion and conventional air insufflation. PATIENTS AND METHODS: A total of 229 patients were randomized to either water immersion or the standard air insertion technique. The primary outcome was success of minimal sedation colonoscopy, which was defined as reaching the cecum without additional sedation, exchange of the adult colonoscope or hands-on assistance for trainees. Patient comfort and satisfaction were also assessed. RESULTS: Successful minimal-sedation colonoscopy was achieved in 51 % of the water immersion group compared with 28 % in the standard air group (OR, 2.66; 95 % CI 1.48 - 4.79; P = 0.0004). Attending physicians had 79 % success with water immersion compared with 47 % with air insufflation (OR, 4.19; 95 % CI 1.5 - 12.17; P = 0.002), whereas trainees had 34 % success with water compared with 16 % using air (OR, 2.75; 95 % CI 1.15 - 6.86; P = 0.01). Using the water method, endoscopists intubated the cecum faster and this was particularly notable for trainees (13.0 +/- 7.5 minutes with water vs. 20.5 +/- 13.9 minutes with air; P = 0.0001). Total procedure time was significantly shorter with water for both experienced and trainee endoscopists ( P < 0.05). Patients reported less intraprocedural pain with water compared with air (4.1 +/- 2.7 vs. 5.3 +/- 2.7; P = 0.001), with a similar level of satisfaction. There was no difference in the neoplasm detection rates between the groups. CONCLUSION: Colonoscopy insertion using water immersion increases the success rate of minimal sedation colonoscopy. Use of the technique leads to a decrease in discomfort, time to reach the cecum, and the amount of sedative and analgesic used, without compromising patient satisfaction.


Subject(s)
Colonoscopy/methods , Hypnotics and Sedatives/administration & dosage , Midazolam/administration & dosage , Pain/drug therapy , Air , Colonoscopy/adverse effects , Conscious Sedation , Humans , Immersion , Insufflation , Pain/etiology , Pain Measurement , Patient Satisfaction , Prospective Studies , Treatment Outcome , Water
6.
Endoscopy ; 40(12): 983-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19065479

ABSTRACT

BACKGROUND AND STUDY AIMS: There is a paucity of in vitro methods for evaluating ERCP accessories. We hypothesize that the time taken to perform a simulated single stent or multiple stents placement is different for stenting systems with or without the capability of intraductal ductal release (IDR) of the guide wire. PATIENTS AND METHODS: We conducted an un-blinded in vitro comparison of ERCP accessories using a mechanical simulator during hands-on ERCP practice workshops. A total of 21 U.S. participants and 20 Chinese participants with various level of ERCP experience took part in the different practice workshops. Accessories with and without the capability of intraductal release of guide wire were compared. Total time required for completing a simulated stenting procedure with single or multiple stents and the respective simulated fluoroscopy time were recorded. RESULTS: There was no significant difference in the time taken for placement of a single stent using either stenting systems. Stenting system capable of intraductal release of the guide wire required significantly shorter time to complete placement of three stents. CONCLUSIONS: Using time required to complete a specific task, i. e. biliary stenting, the mechanical simulator permits the performance of different accessories by the same group of operators to be evaluated objectively.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde/instrumentation , Models, Anatomic , Attitude of Health Personnel , Cholestasis, Extrahepatic/diagnosis , Cholestasis, Extrahepatic/therapy , Common Bile Duct Diseases/diagnosis , Common Bile Duct Diseases/therapy , Curriculum , Education , Equipment Design , Fellowships and Scholarships , Fluoroscopy/instrumentation , Gastroenterology/education , Humans , In Vitro Techniques , Stents , Surveys and Questionnaires , Time and Motion Studies
7.
Aliment Pharmacol Ther ; 26(4): 627-31, 2007 Aug 15.
Article in English | MEDLINE | ID: mdl-17661766

ABSTRACT

BACKGROUND: The direct and indirect costs of sedation limit access to screening colonoscopy amongst United States veterans. AIM: To determine if offering the option of sedation on-demand reduces the need for sedation. Design A retrospective review of prospectively collected performance improvement data in an open access screening colonoscopy programme. SETTING: Performance improvement programme to minimize the burden of sedation at a single VA Medical Center. Subjects 44 consecutive veterans who accepted the option of sedation on-demand. They could choose to have premedications before the start of colonoscopy, or to begin colonoscopy without premedications and receive the medications upon their request during the examination. METHOD: Two experienced endoscopists assisted by experienced nurse assistants performed all of the examinations. Insertion of the colonoscope was aided by infusion of warm water through the colonoscope without air insufflation. Medications were administered at the veterans' request. RESULTS: Offering the option of sedation on-demand to 44 consecutive veterans permitted 52% (N = 23) of the veterans to complete screening colonoscopy without any sedation. CONCLUSIONS: This novel approach of sedation on-demand and water infusion for screening colonoscopy deserves to be further evaluated in a randomized-controlled study amongst patients undergoing colorectal cancer screening.


Subject(s)
Colonic Diseases/diagnosis , Colonoscopy/methods , Colorectal Neoplasms/diagnosis , Conscious Sedation/methods , Mass Screening , Aged , Humans , Middle Aged , Pain Measurement , Patient Acceptance of Health Care , Pilot Projects , Prospective Studies , Retrospective Studies , United States , Veterans
8.
Aliment Pharmacol Ther ; 24(2): 307-12, 2006 Jul 15.
Article in English | MEDLINE | ID: mdl-16842457

ABSTRACT

BACKGROUND: No published Papillotomy Performance Scoring Scale exists. AIMS: To develop such a scale and to apply it to stratify the quality of performance of recorded papillotomies. METHODS: Expert biliary endoscopists were polled regarding their opinion of a 'perfect' biliary papillotomy and experience with complications in relation to the cut axis. Based on these responses a scoring scale encompassing two components - wire alignment and cut orientation, was proposed. This scoring scale was presented to experienced and trainee endoscopists, who scored recording of five biliary papillotomies. The mean final combined score was used for stratification. RESULTS: The experts' opinion of a 'perfect' biliary papillotomy is one cut along the axis of the distal bile duct and papilla. Their reported experience with complications occurring outside of the perfect axis validated their consensus. Application of the scoring scale stratified recorded papillotomies based on the mean final combined scores. CONCLUSIONS: These pilot data support the hypothesis that a scoring scale focused on the cut axis can be constructed based on expert opinion, experience and consensus. The possibility of stratification of mean final combined scores that are significantly different validates application of the scoring scale for assessment of papillotomy performance.


Subject(s)
Biliary Tract Diseases/diagnosis , Sphincterotomy, Endoscopic/standards , Attitude of Health Personnel , Attitude to Health , Biliary Tract Diseases/surgery , Cholangiopancreatography, Endoscopic Retrograde/standards , Clinical Competence/standards , Humans , Observer Variation , Pilot Projects , Reference Values
9.
Aliment Pharmacol Ther ; 23(7): 945-51, 2006 Apr 01.
Article in English | MEDLINE | ID: mdl-16573797

ABSTRACT

BACKGROUND: Caecal intubation can be achieved by extended flexible sigmoidoscopy in 32% of patients. AIM: To assess the feasibility of extended flexible sigmoidoscopy performed by colonoscopists for colorectal cancer screening. METHODS: We enrolled 41 patients referred for screening flexible sigmoidoscopy. After purging, examination was performed with a colonoscope. All patients completed sigmoidoscopy (success in meeting referral goal); 93% and 71% had examination to the transverse or ascending colon, and caecum, respectively. Overall yield and right-sided polyps was 56% and 27%, respectively. Caecal intubation and complete examination with polypectomy took 6.0 +/- 2.5 and 18.3 +/- 5.1 min, respectively; with no complications. Twelve patients requested colonoscope withdrawal because of discomfort. Although 46% reported moderate to severe discomfort, 39% and 36%, respectively, were definitely or probably willing to repeat flexible sigmoidoscopy. RESULTS: Unsedated colonoscopy introduced as extended flexible sigmoidoscopy emphasizes the benefits of added yield rather than the negative image of withholding of discomfort relief. The patient can choose to accept the equivalent of an unsedated colonoscopy or reject the option based on perceived discomfort during extended flexible sigmoidoscopy performed by the colonoscopist. CONCLUSION: Extended flexible sigmoidoscopy is a feasible option in carefully selected patients, fully prepared and by an experienced colonoscopist.


Subject(s)
Colorectal Neoplasms/diagnosis , Sigmoidoscopy/methods , Cecum , Feasibility Studies , Female , Humans , Intestinal Polyps/surgery , Male , Patient Satisfaction , Pilot Projects , Prospective Studies
10.
Aliment Pharmacol Ther ; 20(5): 517-25, 2004 Sep 01.
Article in English | MEDLINE | ID: mdl-15339323

ABSTRACT

BACKGROUND: In animals, hydrochloric acid increases blood flow and mucus secretion in the duodenal mucosa. A significant correlation between index of haemoglobin oxygen saturation and mucosal blood flow, and between change in index of haemoglobin concentration and mucus thickness, respectively, has been demonstrated by reflectance spectrophotometry. AIM: To examine the effect of topical hydrochloric acid upon mucosal blood flow and mucus secretion in the human duodenum. METHODS: This prospective study of 120 patients undergoing routine upper endoscopy, examined the effect of topical 0.1 n hydrochloric acid or 0.9% saline on the duodenal bulb in a randomized, double-blind fashion. Duodenal mucosal index of haemoglobin oxygen saturation and index of haemoglobin concentration were measured by endoscopic reflectance spectrophotometry before and after hydrochloric acid or saline. RESULTS: Baseline index of haemoglobin oxygen saturation, calculated blood flow and index of haemoglobin concentration measurements were comparable between hydrochloric acid (n = 60) and saline (n = 60) treated groups. A history of current use of non-steroidal anti-inflammatory drug was associated with a significantly lower baseline index of haemoglobin oxygen saturation and calculated blood flow. Hydrochloric acid resulted in a significant increase in index of haemoglobin oxygen saturation and calculated blood flow, but a decrease in index of haemoglobin concentration, reflecting an increase in mucus thickness compared with saline. CONCLUSIONS: Our observations in humans confirm data in animal studies that topical exposure to hydrochloric acid induces an increase in duodenal mucosal blood flow and mucus secretion. Post hoc analysis of the data also revealed that attenuation of basal duodenal mucosal blood flow is associated with a history of current non-steroidal anti-inflammatory drug use. Endoscopic reflectance spectrophotometry appears to be adequate to assess factors that influence duodenal defence mechanisms of blood flow and mucus secretion in humans.


Subject(s)
Duodenum/blood supply , Hydrochloric Acid/pharmacology , Mucus/metabolism , Duodenum/metabolism , Humans , Middle Aged , Prospective Studies , Spectrophotometry/methods
11.
Dig Dis Sci ; 46(6): 1217-22, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11414297

ABSTRACT

We tested the hypothesis that stimulation of intestinal mucosal afferent nerves produces an increase in superior mesenteric artery (SMA) but a decrease in mesenteric adipose tissue (MAT) blood flow. In anesthetized rats, blood flow in the SMA (pulsed Doppler flowmetry) and MAT (hydrogen gas clearance) was measured simultaneously before and after administration of 0.9% saline, 640 microM capsaicin, or 5% dextrose into the intestinal lumen. The changes in the SMA were 3.8 +/- 3.0, 15.9 +/- 4.0, and 18.8 +/- 7.6%; and those in the MAT, 4.7 +/- 4.0, -11.5 +/- 3.4, and -0.07 +/- 3.4% of baseline, respectively. The data indicate that exposure of the intestinal lumen to an afferent nerve stimulant or nutrient induced a dichotomous pattern of blood flow changes, an increase in the SMA and a reduction in MAT. The capsaicin-sensitive afferent nerves may be instrumental in mediating these energy responses.


Subject(s)
Adipose Tissue/blood supply , Intestinal Mucosa/innervation , Mesenteric Artery, Superior/physiology , Neurons, Afferent/physiology , Animals , Female , Male , Rats , Rats, Sprague-Dawley , Regional Blood Flow
12.
Dig Dis Sci ; 45(7): 1472-9, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10961733

ABSTRACT

The in vivo immunological events in dextran sulfate sodium (DSS) -induced colitis were evaluated. Rats were fed water (control) or 5% DSS. Colonic sections were assessed by light microscopy, Gram stain, immunohistochemistry, and electron microscopy. A progressive decline in number and increase in fragmentation of bacteria in the colonic lumen was observed over time. Luminal bacteria were the first to show heat shock protein 60 (HSP60) staining (day 3). Macrophages in close proximity to these bacteria were next to show such staining (day 6), and finally the damaged epithelial cells when colitis became severe (day 15). Ultrastructural assessment showed cell-cell contact interactions between macrophages and dendritic gammadelta T cells. An increase in the number of gammadelta T cells and ED1-positive macrophages in the affected colonic tissue over time was documented. These results suggest colonic bacteria, host macrophages, and gammadelta T cells play specific roles in the immunological reactions in DSS-induced colitis, possibly via an HSP60-mediated mechanism.


Subject(s)
Bacteria , Chaperonin 60/physiology , Colitis/chemically induced , Colon/microbiology , Colon/physiology , Dendritic Cells/physiology , Dextran Sulfate , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Animals , Bacteria/immunology , Bacteria/isolation & purification , Colitis/complications , Colon/metabolism , Dendritic Cells/metabolism , Diarrhea/etiology , Immune System/immunology , Immune System/pathology , Macrophages/immunology , Male , Rats , Rats, Sprague-Dawley , Time Factors
13.
Eur J Gastroenterol Hepatol ; 11(11): 1305-10, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10563545

ABSTRACT

OBJECTIVE/BACKGROUND: Non-mitogenic biological activity such as modulation of mucosal blood flow is suspected to convey the protective effects of epidermal growth factor (EGF) in vivo. The aims of our present study were to determine the effects of EGF on colonic mucosal blood flow and injury induced hyperaemia in rats. DESIGN/METHODS: Rats were pretreated with i.p. injections of vehicle, EGF, or indomethacin and EGF prior to mucosal injury. Basal mucosal blood flow and injury induced hyperaemia at the border of the damaged mucosa was determined by using reflectance spectrophotometry. RESULTS: EGF significantly increased basal mucosal blood flow but did not further enhance injury induced hyperaemia. The EGF induced increase in basal mucosal blood flow was completely abolished by indomethacin pretreatment. CONCLUSIONS: EGF induces an increase of basal mucosal blood flow through induction of prostaglandin synthesis. We hypothesize that the increase in mucosal blood flow contributes to the ability of EGF to protect the colonic mucosa against injury.


Subject(s)
Colon/blood supply , Epidermal Growth Factor/pharmacology , Intestinal Mucosa/drug effects , Prostaglandins/physiology , Regional Blood Flow/drug effects , Animals , Blood Pressure/drug effects , Colon/drug effects , Colon/pathology , Cyclooxygenase Inhibitors/pharmacology , Indomethacin/pharmacology , Intestinal Mucosa/blood supply , Intestinal Mucosa/pathology , Male , Rats , Rats, Sprague-Dawley , Regional Blood Flow/physiology
14.
Life Sci ; 63(18): 1653-62, 1998.
Article in English | MEDLINE | ID: mdl-9806218

ABSTRACT

The mesenteric hyperemia induced by intraduodenal application of hydrochloric acid (HCl) is mediated in part by capsaicin-sensitive afferent nerves. Antagonist of capsaicin-sensitive receptors (capsazepine) and blocker of capsaicin-sensitive cation channels (ruthenium red) have been described. We employed these tools to dissect the mechanism of regulation of mesenteric hyperemia induced by intraduodenal administration of HCl. Subcutaneous 100 micromol/kg capsazepine or intraduodenal 0.1% ruthenium red was administered to pentobarbital anesthetized rats. Then, 2.5 ml/kg of 640 microM capsaicin or 0.1 N HCl was administered intraduodenally. The mesenteric hyperemic responses were recorded. The results demonstrated that in a dose that decreased the mesenteric hyperemia induced by intraduodenal capsaicin, capsazepine failed to attenuate the mesenteric vasodilatory effect of intraduodenal HCl. Ruthenium red significantly attenuated the mesenteric hyperemia after intraduodenal capsaicin and HCl. These in vivo data provide the first functional evidence for the existence of capsazepine-sensitive capsaicin receptors and cation channel complexes in the rat duodenal and intestinal mucosa. The capsaicin- and HCl-sensitive receptors are unlikely to be functionally identical in these locations. The ruthenium red-sensitive cation channels appear to mediate the capsaicin- and HCl-induced mesenteric hyperemia.


Subject(s)
Hyperemia/chemically induced , Hyperemia/physiopathology , Mesenteric Arteries/physiopathology , Animals , Blood Pressure/physiology , Capsaicin/analogs & derivatives , Capsaicin/antagonists & inhibitors , Capsaicin/pharmacology , Duodenum/blood supply , Hydrochloric Acid/antagonists & inhibitors , Hyperemia/prevention & control , Laser-Doppler Flowmetry , Male , Rats , Rats, Sprague-Dawley , Regional Blood Flow/physiology , Ruthenium Red/pharmacology
15.
Hepatology ; 27(6): 1530-5, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9620323

ABSTRACT

Glybenclamide, an adenosine triphosphate-dependent potassium (K+(ATP)) channel blocker, lowered portal pressure and attenuated the hyperdynamic splanchnic circulation in rats with partial portal vein ligation (PPVL). The purpose of this report was to confirm these observations and to test the hypothesis that glybenclamide could reduce acidified ethanol-induced gastric mucosal injury in rats with PPVL. Gastric mucosal blood flow (hydrogen gas clearance), systemic blood pressure, and portal pressure were monitored in rats with PPVL or sham operation (SO). Intravenous glybenclamide (20 mg/kg) or vehicle was administered, followed by intragastric acidified ethanol (0.15 N HCl and 15% ethanol). The area of gastric mucosal lesions was assessed by image analysis. In contrast to published findings, there was no significant elevation of portal pressure after glybenclamide administration in rats with PPVL. Glybenclamide did not alter the gastric mucosal hyperemia in these rats. Glybenclamide significantly increased mucosal injury. The data are consistent with the hypothesis that K+(ATP) channels play a role in protecting the gastric mucosa in rats with PPVL.


Subject(s)
Gastric Mucosa/pathology , Gastric Mucosa/physiopathology , Glyburide/pharmacology , Hypoglycemic Agents/pharmacology , Portal Vein/pathology , Potassium Channels/physiology , Animals , Blood Pressure , Gastric Mucosa/blood supply , Hypertension/pathology , Hypertension/physiopathology , Male , Potassium Channels/drug effects , Rats , Rats, Sprague-Dawley , Regional Blood Flow
16.
Dig Dis Sci ; 42(1): 74-8, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9009118

ABSTRACT

To assess the mechanism of the effect of cigarette smoke on ulcer disease we employed a rat model in which cigarette smoke increases the size of acetic acid-induced gastric ulcer and decreases the hyperemia at the ulcer margin. We postulate that cigarette smoke increases angiotensin II (a vasoconstrictor) in ulcer tissue. Since direct measurement of angiotensin II in small tissue samples is problematic, we compared the messenger ribonucleic acid (mRNA) for its precursors (angiotensinogen and renin) in ulcer and normal gastric tissue. We also evaluated the effect of enalapril, which blocks the conversion of angiotensin I to angiotensin II on ulcer size. In the ulcer tissue, cigarette smoke produced a significant increase in mRNA for angiotensinogen but not for renin. Enalapril decreased the size of the gastric ulcer in rats exposed to cigarette smoke. The data support the possibility that in ulcer tissue cigarette smoke stimulates an angiotensin II-mediated mechanism, which may in part be responsible for the impairment of ulcer margin hyperemia and aggravation of ulcer size.


Subject(s)
Angiotensin II/physiology , Smoking/adverse effects , Stomach Ulcer/pathology , Angiotensin II/metabolism , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Enalapril/pharmacology , Immunoblotting , Male , Platelet-Derived Growth Factor/analysis , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Renin/analysis , Somatomedins/analysis , Stomach Ulcer/chemically induced , Stomach Ulcer/metabolism , Transforming Growth Factor beta/analysis
17.
Life Sci ; 61(17): 1713-20, 1997.
Article in English | MEDLINE | ID: mdl-9363987

ABSTRACT

Adenosine triphosphate-dependent potassium (K+ATP) channels in several types of vascular smooth muscles mediate the vasodilation induced by calcitonin gene-related peptide (CGRP). Upon stimulation, primary afferent nerve terminals in the gastric mucosa release CGRP which mediates a protective hyperemia. We tested the hypothesis that a potassium channel blocker aggravates gastric mucosal injury by impairing afferent nerve-mediated hyperemia in the gastric mucosa. Rats were treated with K+ATP channel blocker, glybenclamide (20 mg/kg intravenously). Intragastric added ethanol (0.15 N HCl, 15% ethanol) and intragastric capsaicin (160 microM) were also administered. Glybenclamide aggravated the acidified ethanol-induced mucosal injury, and attenuated the mucosal hyperemia (hydrogen gas clearance) induced by intragastric acidified ethanol and intragastric capsaicin. These findings suggest for the first time that K+ATP channels modulate primary afferent nerve-mediated mucosal defense mechanisms in the gastric mucosa.


Subject(s)
Gastric Mucosa/physiology , Neurons, Afferent/physiology , Potassium Channels/physiology , Animals , Capsaicin/administration & dosage , Ethanol/administration & dosage , Gastric Acid , Gastric Mucosa/drug effects , Gastric Mucosa/innervation , Glyburide/pharmacology , Hyperemia/chemically induced , Male , Rats , Rats, Sprague-Dawley
18.
J Gastroenterol Hepatol ; 12(11): 698-702, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9430032

ABSTRACT

Dextran sulphate sodium (DSS) is an oral agent capable of inducing chronic diarrhoea and colonic inflammation and necrosis in rats. The role of the afferent nerves in this model of colonic mucosal damage is not known. The hypothesis that functional ablation of the capsaicin-sensitive afferent nerves will aggravate DSS-induced colonic damage in rats was tested. Capsaicin pretreatment was used to ablate afferent nerve function and DSS was administered in the drinking water. Control rats received vehicle pretreatment and water without DSS. There were significant correlations between diarrhoea score, mucosal neutrophil infiltration, mucosal necrosis, and anaemia. Capsaicin pretreatment increased diarrhoea score and colonic mucosal neutrophil infiltration in the rats with colonic damage after 2 or 14 days of DSS. In addition, it induced anaemia and mortality in rats after 14 days of DSS. The data supports the hypothesis that functional ablation of the capsaicin-sensitive afferent nerves aggravates the colonic damage induced by DSS.


Subject(s)
Colon/blood supply , Dextran Sulfate/pharmacology , Diarrhea/physiopathology , Neurons, Afferent/physiology , Occult Blood , Animals , Capsaicin/pharmacology , Colon/drug effects , Colon/immunology , Colon/pathology , Diarrhea/chemically induced , Male , Neurons, Afferent/drug effects , Neutrophils/cytology , Rats , Rats, Sprague-Dawley
19.
Dig Dis Sci ; 41(12): 2440-6, 1996 Dec.
Article in English | MEDLINE | ID: mdl-9011455

ABSTRACT

Agents which decrease gastric mucosal blood flow (GMBF) are postulated to have beneficial effects in arresting gastrointestinal bleeding in cirrhotic patients with portal hypertension. Our objective was to test the hypothesis that in a dose that significantly lowers wedged hepatic venous pressure (WHVP), a bolus injection of somatostatin will significantly decrease GMBF in patients with portal hypertensive gastropathy (PHG). In this placebo-controlled, double-blind, crossover study, 20 cirrhotic patients with PHG were randomly assigned to receive either somatostatin followed by placebo (Group A) or placebo followed by somatostatin (Group B). Wedged hepatic venous pressure was monitored. GMBF in the antrum and corpus was assessed by reflectance spectrophotometry. Indices of hemoglobin concentration (IHb) and indices of oxygen content (ISO2) were recorded. Nine patients were assigned to Group A, and 11 to Group B. Mild PHG was seen in 16 patients, and severe PHG in 4 patients. Baseline WHVP, IHb, and ISO2 were similar in both treatment groups. Wedged hepatic venous pressure (WHVP) was significantly lowered [median, 17.6%; interquartile range (-27.0,-12.6%); P = 0.0008] after a 250-microg bolus injection of somatostatin. This dose of somatostatin significantly reduced IHb both in the antrum [-10.2% (-23.4, 0.4%)] and in the corpus [-5.8% (-16.6, 5.6%)] compared to placebo (P = 0.02 and 0.04, respectively). Intravenous bolus injection of 250 microg somatostatin significantly reduces WHVP and GMBF in patients with PHG. Whether this ability to decrease the GMBF in PHG makes somatostatin an effective treatment in acute gastrointestinal bleeding in PHG deserves to be studied.


Subject(s)
Gastric Mucosa/blood supply , Hypertension, Portal/complications , Somatostatin/pharmacology , Stomach Diseases/drug therapy , Aged , Cross-Over Studies , Double-Blind Method , Female , Gastric Mucosa/drug effects , Hemodynamics/drug effects , Hepatic Veins/physiopathology , Humans , Liver Cirrhosis/complications , Male , Middle Aged , Regional Blood Flow/drug effects , Somatostatin/therapeutic use , Stomach Diseases/complications , Venous Pressure/drug effects
20.
Dig Dis Sci ; 41(2): 346-51, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8601381

ABSTRACT

The high incidence of peptic ulcer disease despite decreased acid secretion in the elderly suggests an impairment of mucosal defense mechanism with aging. Stimulation of the intestinal mucosal afferent nerves by intraduodenal application of capsaicin or hydrochloric acid (HCl) increases superior mesenteric artery (SMA) blood flow and protects the duodenal mucosa against deep damage. We tested the hypothesis that the intestinal hyperemia induced by intraduodenal capsaicin or HCL is significantly reduced in older (12 months) rats compared with younger (2 months) rats. Mesenteric blood flow was measured by pulsed Doppler flowmetry in anesthetized rats with the flow probe around the SMA. Two milliliters per kilogram of 160 microM capsaicin or 0.1 N HCl administered intraduodenally increased SMA blood flow significantly in both age groups. The peak response in SMA blood flow, however, was significantly smaller in the older rats than in the younger rats. These observations support the hypothesis that impairment of afferent nerve function occurs with aging in the rat intestine.


Subject(s)
Aging/physiology , Capsaicin/administration & dosage , Duodenum/innervation , Hydrochloric Acid/administration & dosage , Hyperemia/chemically induced , Mesenteric Artery, Superior/drug effects , Afferent Pathways/physiology , Animals , Duodenum/drug effects , Duodenum/physiology , Hydrochloric Acid/pharmacology , Hyperemia/physiopathology , Intestinal Mucosa/drug effects , Male , Rats
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