Ulcerative Esophagitis Research Articles

Alterations in N-methyl-d-aspartate receptor subunits in primary sensory neurons following acid-induced esophagitis in cats

The excitatory amino acid glutamate plays an important role in the development of neuronal sensitization and the ionotropic N-methyl-d-aspartate receptor (NMDAR) is one of the major receptors involved. The objective of this study was to use a cat model of gastroesophageal reflux disease (GERD) to investigate the expression of the NR1 and NR2A subunits of NMDAR in the vagal and spinal afferent fibers innervating the esophagus. Two groups of cats (Acid-7D and PBS-7D) received 0.1 N HCl (pH 1.2) or 0.1 M PBS (pH 7.4) infusion in the esophagus (1 ml/min for 30 min/day for 7 days), respectively. NR1 splice variants (both NH(2) and COOH terminals) and NR2A in the thoracic dorsal root ganglia (DRGs), nodose ganglia (NGs), and esophagus were evaluated by RT-PCR, Western blot, and immunohistochemistry. Acid produced marked inflammation and a significant increase in eosinophil peroxidase and myeloperoxidase contents compared with PBS-infused esophagus. The NR1-4 splice variant gene exhibited a significant upregulation in DRGs and esophagus after acid infusion. In DRGs, NGs, and esophagus, acid infusion resulted in significant upregulation of NR1 and downregulation of NR2A subunit gene expression. A significant increase in NR1 polypeptide expression was observed in DRGs and NGs from Acid-7D compared with control. In conclusion, long-term acid infusion in the cat esophagus resulted in ulcerative esophagitis and differential expressions of NR1 and NR2A subunits. It is possible that these changes may in part contribute to esophageal hypersensitivity observed in reflux esophagitis.

Diagnostic d’œsophagite herpétique à HSV1 chez le sujet immunocompétent par PCR (Herpès Consensus Générique® – Argène). À propos de six cas

We have researched and identified Herpes viruses on the esophageal biopsies taken during the period between September 2006 and March 2008 for 15 suspected patients. The esophageal biopsies were transferred to the laboratory being conserved in physiological serum and frozen at -80 degrees C for PCR. A fragment was conserved for histopathological analysis. The specimen was defrozen and refrozen in liquid azote (to limit the inhibitors) and crushed to the powder form. Extraction was then done following the prerecognised protocol (Herpès Consensus Générique-"Argene"). That kit allows the amplification consensus of the viral genome of the most frequently encountered Herpes family virus: HSV1, HSV2, CMV, VZV, EBV and HHV6. The identification of the implicated virus was done by the Hybridowell Herpes Identification (Argene) kit in parallel with the migration of SDS gel of the obtained amplifications. HSV1 was identified in seven esophageal biopsies between the 15 studied. HHV6 and the association HHV6/EBV for two patients and only one biopsy had inconclusive. The endoscopy and the histopathological examination had confirmed ulcerated esophagitis with cytopathogene aspect in favour of viral infection for six patients. In absence of inhibitors, the adaptation of the extraction technique of the fragments of tissue for few millimetres and the amplifications by PCR had allowed rapid confirmation of the diagnosis of herpetic esophagitis secondary to HSV1 even before the results of the histopathological examination. Treatment by acyclovir entrained regression of the disease.

Management of gastro-oesophageal reflux disease in childhood

Gastro-oesophageal reflux disease (GORD) is common in children. The clinical presentation varies for different paediatric age groups. Minor gastro-oesophageal reflux is considered physiological in infancy but requires treatment if reflux oesophagitis, haematemesis, feeding difficulties, failure to thrive or respiratory manifestations are present. CP, cystic fibrosis and oesophageal atresia are associated with an increased incidence of GORD. In neurologically impaired children, GORD may be severe and cause ulcerative oesophagitis or chronic pulmonary aspiration. The diagnosis of GORD is based on clinical observation, as well as investigations (e.g. barium meal, oesophageal pH monitoring, gastroscopy and nuclear medicine studies). GORD in infancy may be caused by cow’s milk allergy. Eosinophilic oesophagitis, a chronic from of oesophagitis associated with food allergy and atopy, may mimic GORD. Complications of longstanding, untreated GORD include peptic oesophageal strictures, Barrett’s metaplasia and adenocarcinoma. Treatment of GORD relies on dietary interventions, acid suppressive medications and motility agents. In severe cases, a surgical antireflux procedure (fundoplication) may be required. The prognosis of infantile GORD is generally good, and clinical remission usually occurs between 12 and 18 months of age. In older children, GORD is likely to persist to adult life.

Mycophenolate Mofetil-related Gastrointestinal Mucosal Injury: Variable Injury Patterns, Including Graft-versus-Host Disease-like Changes

Mycophenolate mofetil (MMF) is a commonly used immunosuppressive drug used in the management of transplant recipients. Although gastrointestinal (GI) toxicity is a known complication of MMF, the literature characterizing the pathologic features of MMF in the GI tract is sparse. This study characterizes the pathologic features of MMF toxicity in both the upper and lower GI tract, correlating it with clinical and endoscopic findings. Seventy-five GI biopsies (9 esophageal, 15 gastric, 16 duodenal, 5 ileal, 30 colonic) from 46 transplant recipients from 2002 to 2006 were obtained and assessed for multiple histologic features. Clinical features were recorded for all cases and endoscopic findings. Only MMF patients showed ulcerative esophagitis (5/7 cases) and reactive gastropathy (4/10 cases). Only MMF patients showed graft-versus-host disease (GVHD)-like features in duodenal (4/12 cases) and ileal (1/5 cases) biopsies. GVHD-like changes were seen more frequently among patients on MMF compared with those not on MMF [9 (56%) vs. 2 (14%); P=0.017]. Crypt architectural disarray [12 (75%) vs. 2 (14%); P=0.001], lamina propria edema [9 (56%) vs. 2 (14%); P=0.017], increased lamina propria inflammation [13 (81%) vs. 3 (21%); P=0.001], dilated damaged crypts [7 (44%) vs. 1 (7%); P=0.024], and increased crypt epithelial apoptosis [9 (56%) vs. 2 (14%); P=0.017] were more common with MMF patients compared with non-MMF patients. In conclusion, pathologists should be aware of the potential manifestations of MMF toxicity throughout the GI tract, including ulcerative esophagitis, reactive gastropathy, and GVHD-like features in intestinal biopsies.

Chronic Diarrhea

Purpose: Gastrointestinal (GI) involvement in SLE is not uncommon. However, SLE is often overlooked in the differential diagnosis of patients who present with certain GI symptoms. We describe a case of chronic diarrhea as the predominant presenting feature of SLE. Methods: N/A Results: A 63 year-old African American lady was admitted repeatedly to the hospital with nausea, vomiting and diarrhea over 5 months. She had no arhralgias or swelling. The patient appeared cachectic with satisfactory vitals, conjuncivae were pale, and FOBT was (+). Labs showed a hemoglobin 8 g/dl, BUN 40 mg/dl, creatinine 3.1 mg/dl, magnesium 1.3 mg/dl and potassium 2.7 mmol/l. Urine analysis showed hematuria, pyuria and nephrotic range proteinuria. Further investigations revealed iron, folate and vitamin D deficiency. Stools had no pathogens or parasites. Poor tolerance of a 100 g/day fat diet precluded 72-hour fecal fat test. Kidney ultrasound disclosed hydronephrosis without stones. An upper endoscopy and colonoscopy demonstrated ulcerative esophagitis with esophageal and gastric stasis. Small bowel and colon biopsies were unremarkable including a Congo red stain. Her hydronephrosis and obstructive uropathy required bilateral ureteral stent placement and an indwelling Foley catheter. Her diarrhea was treated with cholestyramine and electrolyte replacement without success. Because of the multi-organ involvement, further investigations for paraproteinemia and autoimmune disease were undertaken. Serologic studies revealed a positive ANA and a positive anti-dsDNA and anti-Smith antibodies. Her anemia, proteinuria and the positive antibodies were all consistent with the diagnosis of systemic lupus erythematosus. Therapy with corticosteroids was started, with an excellent response; the diarrhea subsided within 48 hours, and the patient regained weight and strength. Conclusion: Gastrointestinal symptoms account for 25–40% of the presenting clinical manifestations of SLE. It can affect the entire GI tract. However, GI symptoms as the sole presentation of SLE are a rare phenomenon. Chronic diarrhea in SLE can be secondary to colitis, celiac disease, protein losing enteropathy, or malabsorption. Interestingly, the random gastrointestinal biopsies in our patient did not show any significant pathological abnormalities. We hypothesize that our patient may have had either patchy small bowel disease or possibly malabsorbtion from dysmotility. Moreover, there are a few reports in the literature on the association of obstructive uropathy and intestinal malabsorption in SLE patients. This case highlights chronic diarrhea with obstructive uropathy as a possible, albeit unusual, presentation of SLE.

Phase I study of sunitinib in combination with carboplatin (C) plus paclitaxel (P) in patients (pts) with advanced solid tumors (STs)

3565 Background: Sunitinib (SU) is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs-1, -2, and -3, PDGFRs-α and -β, KIT, FLT3, CSF-1R and RET. SU is approved for the treatment of advanced RCC and imatinib-resistant/intolerant GIST and has demonstrated antitumor activity in patients with other advanced STs. This study evaluated the safety and efficacy of SU in combination with C/P. Methods: Pts with advanced STs for whom curative therapy was not available were enrolled. Serial pt cohorts received escalating daily doses of oral SU at 25, 37.5, or 50 mg for 2 wks of a repeated 3-wk cycle (2/1 schedule) or for continuous 3 wk cycles (CD schedule) in combination with C (AUC=6 mg·min/mL) plus P (175–225 mg/m2) given every 21 days. The maximum tolerated dose (MTD) of SU plus C/P was assessed based on observed dose limiting toxicities (DLTs) and adverse events (AEs). Results: As of Dec 2007, 15 pts were enrolled in the 2/1 schedule [25 mg (n=9) and 37.5 mg (n=6)] and 6 pts in the CD schedule [25 mg (n=3) and 37.5 mg (n=3)] both in combination with C/P (175 mg/m2). The median age for all enrolled pts was 59 yrs (range 37–76) and 43% of pts had received multiple prior systemic treatments. Pts enrolled had various STs, including pancreatic (n=4), NSCLC (n=3), SCLC (n=3), mesothelioma (n=3) and melanoma (n=3). Of the 15 pts enrolled in the 2/1 schedule, 4 pts were not evaluable for DLTs due to early discontinuation prior to start of C/P. There was one DLT observed at 25 mg in the 2/1 schedule (grade 4 ischemic optic neuropathy) and two DLTs at 37.5 mg (fatal GI hemorrhage and grade 3 neutropenic infection). The most commonly observed Grade 3/4 hematologic abnormalities (both schedules) included neutropenia (n=13) and lymphopenia (n=12). Other Grade 3/4 AEs included fatigue (n=2), thrombosis (n=1), ulcerative esophagitis (n=1) and syncope (n=1). Of the evaluable pts (both schedules), 1 pt with SCLC had a confirmed PR. Conclusions: These data suggest that the dose levels tested to date are tolerable in patients with advanced STs and may represent a clinically useful treatment option. The determination of MTD, safety, and efficacy of SU plus C/P are under further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer AstraZeneca, Aventis, Genentech, GlaxoSmithKline, Pfizer, Takeda Pfizer AstraZeneca, Aventis, Genentech, GlaxoSmithKline, Pfizer, Takeda Amgen, Ariad, Array Biopharma, AstraZeneca, Boeringer Ingelheim, Bristol-Myers Squibb, Endocyte, Exelixis, Genentech, GlaxoSmithKline, ImClone, Merck, NCI, Nereus, Novartis, Pfizer, Roche, sanofi-aventis, Ziopharm

Impact of Gastro-esophageal Reflux on Mucin mRNA Expression in the Esophageal Mucosa

IntroductionChanges in the expression of mucin genes in the esophageal mucosa associated with uncomplicated gastro-esophageal reflux disease have not been evaluated even though such changes could be associated with reflux-induced mucosal damage. We therefore sought to identify reflux-induced changes in mucin gene expression using a cell line and biopsies from the esophageal mucosa in patients with and without reflux. MethodsMUC-1, MUC-3, MUC-4, and MUC-5AC gene expressions were investigated in the HET-1A cell line following exposure to acid (pH 4) and/or bile (120μm of a bile salt milieu), and in esophageal mucosal biopsies from controls, subjects with non-erosive gastro-esophageal reflux, and subjects with reflux associated with ulcerative esophagitis (erosive). The mucosal biopsies were also evaluated for IL-6 mRNA expression (inflammatory marker) and CK-14 mRNA expression (mucosal basal cell layer marker). Gene expression was determined using real-time reverse transcriptase-polymerase chain reaction analysis. ResultsIn the cell line studies, there were differences in mRNA levels for all of the evaluated mucins following treatment with either acid or the acid and bile combination. In the studies which evaluated tissue specimens, IL-6 and CK-14 mRNA levels increased according to degree of reflux pathology. The expression of MUC-1 and MUC-4 in mucosa from patients with erosive reflux was lower than in subjects without reflux and in patients with non-erosive reflux, whereas the expression of MUC-3 and MUC-5AC was increased (although these differences did not reach significance at p < 0.05). When mRNA expression data for tissue samples from all groups were combined, significant correlations were identified between IL-6 vs. CK-14 and IL-6 vs. MUC-3, MUC-3 vs. CK-14 and MUC-3 vs. MUC-5AC, and for MUC-1 vs. MUC-5AC. The correlation between IL-6 and CK-14 was also significant within the control and non-erosive reflux groups. The correlation between IL-6 and MUC-3 was significant within the control and erosive reflux groups, and the correlation between MUC-1 and MUC-5AC was significant within the erosive reflux group. ConclusionsThe results of this study suggest that the profile of mucin expression in the esophageal mucosa is influenced by the pH and composition of the gastro-esophageal reflux. Further work should explore the response of these genes to acid and bile reflux, and their role in the etiology of mucosal damage in gastro-esophageal reflux.

Gastric Epithelial Cell Modality and Proton Pump Inhibitor

Proton pump inhibitors (PPIs) are now commonly used for the treatment of acid related diseases such as peptic ulcer and reflux esophagitis. Because of their ability to produce direct inhibition of the proton pump, PPIs provide more sustained increase of the gastric pH than H2-receptor (H2R) antagonists. Diverse reports have been published on gastric epithelial cell modality associated with PPI treatment both in animal models and clinical settings. The present review summarizes the recent accumulated evidence on gastric epithelial cell modality associated with PPI treatment, including the formation of gastric carcinoid tumors and fundic gland polyps, and the development of gastric mucosal atrophy. Long-term PPI treatment has been reported to cause enlargement of the parietal cells and enterochromaffin-like cells, and to decrease the number of chief cells without affecting A-like cell. Although the development of gastric carcinoid tumors after chronic PPI treatment has been reported in animal studies, no such occurrences have been demonstrated in humans. The effect of PPIs on the formation of fundic gland polyps and the development of atrophic gastritis should be investigated in future studies.

Alendronate-Induced Esophagitis: Possible Pathogenic Role of Hypersensitivity to Alendronate

Upper gastrointestinal tract mucosal irritations, such as esophagitis, have been reported as rare adverse events due to a variety of aminobisphosphonates, including alendronate sodium, which have been widely used to treat osteoporosis. Although the pathogenesis of aminobisphosphonate-induced esophageal mucosal irritation has not been clearly understood, direct chemical esophageal irritation with prolonged local mucosal exposure to the drug with gastric contents might be the most plausible mechanism according to the previously reported literature. Here we report a young adult man with severe ulcerative esophagitis due to alendronate who demonstrated a strongly positive result on a drug lymphocyte stimulation test against alendronate. This case report provides the new concept that T-cell mediated delayed hypersensitivity to the drug may be involved in the pathogenesis of alendronate-induced esophagitis.

Esophageal Intramural Pseudodiverticulosis

A 59-year-old-man without significant medical history presented with a 5-year history of progressive dysphagia for solid foods. An upper endoscopy, performed 5 years earlier in another hospital, showed a benign esophageal stricture with Candida albicans infection. He was treated with antifungal drugs, but he refused further investigations for several years. Because he was unable to swallow solids, he presented for further investigation at our institution. Apart from a significant weight loss of 15 kg over several months, the patient had no symptoms. Physical examination was unremarkable, except for a body weight of 45 kg (body mass index, 15.6 kg/m2). Upper endoscopy revealed a stricture between 23 and 29 cm of the incisors that barely could be passed with a pediatric endoscope. The mucosa of the upper esophagus was inflammatory with several small white spots, suggestive for fungal infection. No signs of peptic esophagitis were present at the gastroesophageal junction; stomach and duodenum were normal. Biopsy specimens taken from the stricture showed an ulcerated esophagitis and confirmed the presence of mycosis. Barium esophagogram was pathognomonic for esophageal intramural pseudodiverticulosis (Figure). Esophageal intramural pseudodiverticulosis is a benign condition of which only about 250 cases have been reported worldwide. The condition is characterized by multiple flask-shaped outpouchings in the esophageal wall. These pseudodiverticula, formed by dilatation of the esophageal submucosal glands, typically are diagnosed on barium esophagogram.1Teraishi F. Fujiwara T. Jikuhara A. et al.Esophageal intramural pseudodiverticulosis with esophageal strictures successfully treated with dilation therapy.Ann Thorac Surg. 2006; 82: 1119-1121Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar In many cases the multiple small orifices of the intramural pseudodiverticula can be appreciated on endoscopy.2Hahne M. Schilling D. Arnold J.C. et al.Esophageal intramural pseudodiverticulosis: review of symptoms including upper gastrointestinal bleeding.J Clin Gastroenterol. 2001; 33: 378-382Crossref PubMed Scopus (46) Google Scholar Computerized tomography sometimes shows esophageal wall thickening with diffuse irregularity of the lumen and intramural gas collection. Presenting symptoms are dysphagia and bleeding, but patients may remain asymptomatic.2Hahne M. Schilling D. Arnold J.C. et al.Esophageal intramural pseudodiverticulosis: review of symptoms including upper gastrointestinal bleeding.J Clin Gastroenterol. 2001; 33: 378-382Crossref PubMed Scopus (46) Google Scholar Even though esophageal intramural pseudodiverticulosis is a benign condition, severe complications including fistula formation, perforation, and mediastinitis have been reported. As was the case in our patient, the condition often is complicated by stricture formation. Treatment of the inflammation and endoscopic dilatation of the stenosis is an effective therapy for the dysphagia. Our patient was treated successfully with endoscopic dilatation. Six months after dilatation, he remains asymptomatic and has gained weight.

Celecoxib Plus Aspirin Versus Naproxen and Lansoprazole Plus Aspirin: A Randomized, Double-Blind, Endoscopic Trial

Patients requiring low-dose aspirin along with nonsteroidal anti-inflammatory drugs are at increased risk for gastrointestinal injury. This study compared the incidence of gastroduodenal ulcers in patients treated with low-dose aspirin and a cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug or a nonselective nonsteroidal anti-inflammatory drug plus the proton pump inhibitor lansoprazole. Subjects 18 years or older with osteoarthritis, without gastroduodenal ulcer or erosive esophagitis at baseline endoscopy, and a cardiovascular indication for prophylaxis low-dose (81 or 325 mg) aspirin were prescribed open-label aspirin and blindly randomized to celecoxib 200 mg/day or naproxen 500 mg twice daily plus lansoprazole 30 mg once daily. Endoscopy was performed at 12 weeks or early termination. One thousand forty-five subjects were randomized and received at least 1 dose of study medication, and 854 (n = 426 celecoxib, n = 428 naproxen plus lansoprazole) subjects with both baseline and final visit endoscopies were evaluable for the primary efficacy analysis. Among these subjects, the rate of endoscopically confirmed gastroduodenal ulcers was not different in the celecoxib (9.9%) and naproxen plus lansoprazole (8.9%; treatment difference [95% confidence interval], 1.0% [-2.9% to 4.9%]) groups. In patients with osteoarthritis taking low-dose aspirin, the use of celecoxib or naproxen plus lansoprazole resulted in similar rates of gastroduodenal ulceration.

Role of gastroscopy in gastro-oesophageal reflux disease (GORD)

AbstractBackgroundThis two-year study is a retrospective analysis of records of patients diagnosed with gastro-oesophageal reflux disease (GORD) at a private medical aid society for the period January 2002 to December 2003. In this study of GORD and its complications, the use of gastroscopy as a staging criteria and the cost of treatment were evaluated. Patients with alarming symptoms (chronic gastrointestinal bleeding, progressive unintentional weight loss, progressive difficulty in swallowing, persistent vomiting, iron deficiency anaemia, epigastric mass or suspicious barium meal), those with complications of GORD (erosive oesophagitis, ulcerative oesophagitis, oesophageal strictures, Barrett's oesophagus and oesophageal adenocarcinoma), and patients in whom symptoms have not resolved need to have a gastroscopy performed. If left untreated, some of these symptoms could lead to more severe and serious complications. Accurate recognition of these symptoms will help to identify, evaluate and treat patients...

Bone marrow progenitor cells contribute to esophageal regeneration and metaplasia in a rat model of Barrett’s esophagus

Barrett's esophagus develops when refluxed gastric juice injures the esophageal squamous lining and the injury heals through a metaplastic process in which intestinal-type columnar cells replace squamous ones. The progenitor cell that gives rise to Barrett's metaplasia is not known, nor is it known why the condition is predisposed to malignancy. We studied the contribution of bone marrow stem cells to the development of Barrett's esophagus in an animal model. Twenty female rats were given a lethal dose of irradiation followed by tail vein injection of bone marrow cells from male rats. Ten days later, the female rats were randomly assigned to undergo either esophagojejunostomy, a procedure that causes reflux esophagitis with intestinal metaplasia, or a sham operation. The rats were killed at 8 weeks and serial sections of the snap-frozen esophagi were cut and mounted on slides. The first and last sections were used for histological evaluation and the intervening sections were immunostained for cytokeratin to identify epithelial cells and analyzed for Y chromosome by fluorescence in situ hybridization (FISH). Histological evaluation of the esophagi from rats that had esophagojejunostomy revealed ulcerative esophagitis and multiple areas of intestinal metaplasia. FISH analyses showed that some of the squamous epithelial cells and some of the columnar epithelial cells lining the glands of the intestinal metaplasia were positive for Y chromosome. These observations suggest that multi-potential progenitor cells of bone marrow origin contribute to esophageal regeneration and metaplasia in this rat model of Barrett's esophagus.

Appropriateness of Upper Gastrointestinal Endoscopy in Children: A Retrospective Study

Upper gastrointestinal endoscopy (UGIE) is appropriate in many situations in adults and children. Recommendations for UGIE use in children were published recently by the French-language Paediatric Hepatology, Gastroenterology, and Nutrition Group (GFHGNP). We retrospectively reviewed the 293 UGIE procedures undertaken in 251 children between January 1, 2001 and June 30, 2003 by 2 senior endoscopists. The UGIE procedures were categorized as appropriate or inappropriate based on GFHGNP recommendations, and diagnostic efficiency was compared in the 2 groups with the chi2 test followed by multivariate logistic regression analysis. Of the 293 UGIE procedures, 52 (17.7%) were considered inappropriate. Diagnostic efficiency was 51% in the appropriate group versus 17.3% in the inappropriate group (odds ratio, 4.2; 95% CI, 2-8.7; P < 10(-3)). The proportion of appropriate UGIE procedures was higher among inpatients than outpatients (odds ratio, 2.51; 95% CI, 1.24-5.08; P = 0.01). Inappropriate reasons for performing UGIE included isolated failure to thrive and follow-up after neonatal esophagogastroduodenitis. Nine inappropriate UGIE procedures contributed useful information: ulcerative esophagitis in 1 patient, hemorrhagic esophagitis in 4 patients, duodenitis in 1 patient, and malabsorption in 3 patients caused in 1 case by cow's milk allergy and in 2 cases to fully documented celiac disease. UGIE was usually performed appropriately in our pediatric hospital. Inappropriate UGIE procedures were more common in outpatients than in admitted patients. Awareness of the recommendations for appropriate UGIE use needs to be improved among office-based and hospital-based physicians.

Influence of overweight and obesity on upper endoscopic findings

In previous studies, increasing body mass index (BMI, kg/m(2)) was related to chronic gastrointestinal symptoms, such as frequent vomiting, upper abdominal pain, bloating and diarrhea. However, there have been no reports about the relationship between increasing BMI and abnormal upper endoscopic findings such as gastritis or ulcer. The study group consisted of 27 319 individuals who underwent medical checkup at a healthcare center from 1 January to 31 December 2003. The following classification of BMI was applied. (i) underweight; BMI < 18.5; (ii) normal weight; 18.5 <or= BMI < 25.0; (iii) overweight; 25.0 <or= BMI < 30.0; and (iv) obese; BMI >or= 30.0. The subjects were grouped according to the findings of upper endoscopy as follows: group 1, those with erosive gastritis, gastric ulcers (benign and malignant) and duodenal ulcers; group 2, those with reflux esophagitis; and group 3, those with findings of upper endoscopy other than group 1 and group 2. The prevalence of obesity and overweight was 2.2% and 30.5%, respectively. By multivariate analyses, overweight (OR 1.31, 95% CI; 1.22-1.40, P = 0.000) and obesity (OR 1.40, 95% CI; 1.14-1.72, P = 0.001) were significant contributors of group 1. Overweight (OR 1.61, 95% CI; 1.42-1.83, P = 0.000) and obesity (OR 2.23, 95% CI; 1.59-3.11, P = 0.000) were also significant contributors of group 2. In the general population, increasing BMI was associated with abnormal upper endoscopic findings, such as erosive gastritis, gastric ulcer, duodenal ulcer and reflux esophagitis. Clarification of the cause-and-effect relationships and the mechanisms of these associations require further investigation.

A low prevalence ofH pyloriand endoscopic findings in HIV-positive Chinese patients with gastrointestinal symptoms

To compare the prevalence of H pylori infection, peptic ulcer, cytomegalovirus (CMV) infection and Candida esophagitis in human immunodeficiency virus (HIV)-positive and HIV-negative patients, and evaluate the impact of CD4 lymphocyte on H pylori and opportunistic infections. A total of 151 patients (122 HIV-positive and 29 HIV-negative) with gastrointestinal symptoms were examined by upper endoscopy and biopsy. Samples were assessed to determine the prevalence of H pylori infection, CMV, candida esophagitis and histologic chronic gastritis. The prevalence of H pylori was less common in HIV-positive patients (22.1%) than in HIV-negative controls (44.8%; P < 0.05), and the prevalence of H pylori displayed a direct correlation with CD4 count stratification in HIV-positive patients. In comparison with HIV-negative group, HIV-positive patients had a lower incidence of peptic ulcer (20.7% vs 4.1%; P < 0.01), but a higher prevalence of chronic atrophy gastritis (6.9% vs 24.6%; P < 0.05)ìCandida esophagitis and CMV infection. Unlike HIV-negative group, H pylori infection had a close relationship to chronic active gastritis (P < 0.05). In HIV-positive patients, chronic active gastritis was not significantly different between those with H pylori infection and those without. The lower prevalence of H pylori infection and peptic ulcer in HIV-positive patients with gastrointestinal symptoms suggests a different mechanism of peptic ulcerogenesis and a different role of H pylori infection in chronic active gastritis and peptic ulcer. The pathogen of chronic active gastritis in HIV-positive patients may be different from the general population that is closely related to H pylori infection.

Twenty-Five Years of Rehabilitation of Odontocetes Stranded in Central and Northern California, 1977 to 2002

Rehabilitation of stranded cetaceans is receiving increasing attention and involves considerable financial and personnel resources, although the survival rate appears to be low. To evaluate rehabilitation success, we examined 25 years (1977 to 2002) of data on live-stranded odontocetes (n = 70) from northern California that were rescued for rehabilitation. Thirty-five animals (50%) died within the first 24 h of being rescued, 13 animals (19%) died within the first week, seven animals (10%) died within a month, and five animals (7%) survived longer than one month, but subsequently died. Three animals (4%) were deemed nonreleasable and placed into captivity, whereas five animals (7%) were released back into the wild. Two animals (3%) were relocated and released; these animals were never seen again. Clinical signs were nonspecific, and it was difficult to differentiate medical problems that resulted from stranding from those that may have caused the stranding. Causes of death included pneumonia (n = 16), septicemia (n = 6), encephalitis (n = 3), maternal separation (n = 7), and blunt trauma (n = 6). No morbilliviral inclusion bodies or typically associated lesions were detected. Cause of death was unknown for 23 cases. Myocardial degeneration and contraction band necrosis (n = 9) and nephrosis (n = 4) probably resulted from the stress of stranding. Ulcerative glossitis and esophagitis were observed in most animals that were tube-fed in rehabilitation. Four animals that had been in rehabilitation for more than 1 wk had rhabdomyolysis and one had scoliosis. These data indicate that the success of rehabilitating and releasing stranded odontocetes in California is minimal, and the stress of stranding and rehabilitation in addition to pre-existing disease can result in morbidity and mortality. Of the animals released, two common dolphins (Delphinus delphis) and one harbor porpoise (Phocoena phocoena) were tagged with satellite transmitters. Transmissions were received for up to 5 mo after release. Increased use of telemetry is essential for post-release monitoring and evaluating rehabilitation success.

Histopathologic Evaluation of an Animal Model for Barrett’s Esophagus and Adenocarcinoma of the Distal Esophagus

Barrett's esophagus and adenocarcinoma of the esophagus are related to long-standing duodeno-gastroesophageal reflux. The development of an animal model in which Barrett's esophagus and/or carcinoma is induced by duodeno-(gastro-)esophageal reflux could provide better understanding of the pathogenesis of the metaplasia-dysplasia-carcinoma sequence and would create the possibility of investigating new treatment strategies for this aggressive disease. Two rat models were analyzed. In the first experiment, 44 male Sprague Dawley rats underwent end-to-side esophagojejunostomy with gastric resection, to ensure duodenoesophageal reflux without gastric acid. In the second experiment a side-to-side esophago-gastrojejunostomy was performed in 30 rats, ensuring duodeno-gastroesophageal reflux. In both experiments animals were not exposed to any exogenous carcinogens during the experiment. Sequential morphological changes (i.e., esophagitis, intestinal metaplasia, dysplasia, and carcinoma) were studied after 4, 6, and 12 months. To analyze histopathologic characteristics, evaluation of the hematoxylin and eosin specimens was combined with immunohistochemical stainings for high-iron diamine-alcian blue, alcian blue/periodic acid-Schiff, the proliferation marker PCNA, and mutations in the tumor suppressor gene p53. In the first experiment, only 11 animals survived the postoperative period. These animals had to be sacrificed at a median of 11 weeks due to persistent weight loss and failure to thrive. Severe ulcerative esophagitis was seen in all animals, with a 2-mm segment of metaplastic epithelium found at the anastomosis. In four animals a large, well-differentiated, mucinous tumor without malignant characteristics was observed. In the second experiment, eight animals died postoperatively. Twelve animals were sacrificed according to protocol at 4 or 6 months. In these animals, extensive esophagitis with squamous cell hyperplasia was found. In addition, a short (2 mm) segment of metaplastic epithelium was observed, without dysplasia. The remaining animals survived 1 year. After 1 year, 9 of the 10 animals had developed a glandular metaplastic segment (median length, 10 mm), which was histologically and immunohistologically characteristic for the specialized columnar epithelium of Barrett's esophagus without signs of dysplasia. Finally, in seven animals a mucinous tumor with cytologic characteristics of a well-differentiated mucinous adenocarcinoma was found without infiltrative growth. These tumors were always found at the site of the anastomosis, originated in the submucosa, and did not reach either the luminal surface or the muscular layer. The mucinous lesions were not positive for p53, and PCNA was only slightly increased. Although they showed cytological characteristics of malignancy, histopathologic evaluation was more suggestive of a reactive mucous producing lesion fitting the diagnosis "esophagitis cystica profunda." This study demonstrates the development of a long Barrett's segment in an animal duodeno-gastroesophageal reflux model. Although mucinous tumors resembling adenocarcinomas develop around the anastomosis, these are probably not reflux induced and are more likely to be reactive lesions. However, the true nature of these tumors remains to be elucidated.

Pathophysiological characteristics of the various forms of gastro-oesophageal reflux disease: Spectrum disease or distinct phenotypic presentations?

Background The traditional approach to gastro-oesophageal reflux disease as a spectrum disease has recently been criticised and the distinct phenotypic presentations model has been proposed. Aim To evaluate the main pathophysiological characteristics of various gastro-oesophageal reflux disease presentations. Methods Oesophageal manometry and 24-h pH-monitoring were performed in a gastro-oesophageal reflux disease series collected in a 7-year period. Results Four hundred and twenty-one subjects were studied. Mean total percentage acid reflux time was significantly higher in long-segment Barrett's oesophagus and in ulcerative oesophagitis than in all the other gastro-oesophageal reflux disease groups, whilst in short-segment Barrett's oesophagus results were quite similar to those found in non-erosive reflux disease and in erosive reflux disease. Patients with ulcerative oesophagitis and long-segment Barrett's oesophagus were older than all the other gastro-oesophageal reflux disease groups. The mean lower oesophageal sphincter pressure was significantly reduced in non-erosive reflux disease, erosive reflux disease, ulcerative oesophagitis, short-segment Barrett's oesophagus and long-segment Barrett's oesophagus as compared with functional heartburn and hypersensitive oesophagus and with controls. Conclusions In keeping with the spectrum model of gastro-oesophageal reflux disease, severity of acid reflux increases from non-erosive reflux disease through erosive reflux disease up to ulcerative oesophagitis and long-segment Barrett's oesophagus. Ulcerative oesophagitis and long-segment Barrett's oesophagus could represent an advanced step in the natural history of gastro-oesophageal reflux disease. Our results do not confirm the distinct phenotypic presentations hypothesis.

Capsaicin receptor (TRPV1) and non-erosive reflux disease

Non-erosive reflux disease (NERD) is a common and heterogeneous disorder. We hypothesized that changes in peripheral innervation may lead to hyperalgesia and contribute to the development of the disorder. Patients referred for evaluation of reflux symptoms with wireless pH monitoring were asked to provide demographic and clinical data and complete a survey related to severity of reflux symptoms. Endoscopies were performed to rule out macroscopic abnormalities of the esophageal mucosa. Biopsies obtained 2 cm above the gastroesophageal junction were stained for protein gene product 9.5 (PGP 9.5; general neuronal marker) and TRPV1 (capsaicin receptor) immunoreactivity. The density of immunoreactive fibers in the esophageal mucosa was determined morphometrically. A total of 39 patients without evidence of Barrett's metaplasia, erosive or ulcerative esophagitis were enrolled. Most patients had daily symptoms. The total esophageal acid exposure time was 5.6+/-0.6%, with 16 patients (41%) having increased acid reflux. Immunoreactivity for PGP 9.5 or TRPV1 was detected in papillary structures as well as within the epithelium (free intra-epithelial endings). Total acid-exposure time, but not symptom score or duration correlated significantly with density of PGP 9.5 immunoreactivity and TRPV1 positive fibers. Even in the absence of macroscopic injury, esophageal acid exposure is associated with changes in mucosal innervation of the esophagus, thus potentially further enhancing symptoms in patients with gastroesophageal reflux.