Gastroduodenal Lesions Research Articles

Comparison of Fusion Imaging Using a Combined SPECT/CT System and Intra-arterial CT: Assessment of Drug Distribution by an Implantable Port System in Patients Undergoing Hepatic Arterial Infusion Chemotherapy

Hepatic arterial infusion (HAI) chemotherapy is effective for treating primary and metastatic carcinoma of the liver. We compared the perfusion patterns of HAI chemotherapy on intra-arterial port-catheter computed tomography (iapc-CT) and fused images obtained with a combined single-photon emission computed tomography/computed tomography (SPECT/CT) system. We studied 28 patients with primary or metastatic carcinoma of the liver who bore an implantable HAI port system. All underwent abdominal SPECT using Tc-99m-MAA (185 Mbq); the injection rate was 1 mL/min, identical to the chemotherapy infusion rate, and 0.5 mL/sec for iapc-CT. Delivery was through an implantable port. We compared the intrahepatic perfusion (IHP) and extrahepatic perfusion (EHP) patterns of HAI chemotherapy on iapc-CT images and fused images obtained with a combined SPECT/CT system. In 23 of 28 patients (82%), IHP patterns on iapc-CT images and fused images were identical. In 5 of the 28 patients (18%), IHP on fusion images was different from IHP on iapc-CT images. EHP was seen on fused images in 12 of the 28 patients (43%) and on iapc-CT images in 8 patients (29%). In 17 patients (61%), upper gastrointestinal endoscopy revealed gastroduodenal mucosal lesions. EHP was revealed on fused images in 10 of these patients; 9 of them manifested gastroduodenal toxicity at the time of subsequent HAI chemotherapy. Fusion imaging using the combined SPECT/CT system reflects the actual distribution of the infused anticancer agent. This information is valuable not only for monitoring adequate drug distribution but also for avoiding potential extrahepatic complications.

Risk Assessment and Outpatient Management in Bleeding Peptic Ulcer

1) To review clinical and endoscopic variables in patients hospitalized for upper gastrointestinal bleeding (UGIB) due to peptic gastroduodenal lesions over a period of 3 years; 2) to identify factors associated with unfavorable evolution; and 3) to evaluate characteristics of patients discharged immediately after endoscopy. A 3-year retrospective analysis of all UGIB episodes was performed. Patients with gastroduodenal ulcer or erosive gastritis/duodenitis at endoscopy were included. The prognostic value of several clinical, endoscopic, and analytical variables was assessed. Persistence or recurrence of bleeding, surgery, and mortality were considered as outcome variables (evolution was classified as "unfavorable" when any of these was observed). A total of 341 patients were identified, with a mean age of 62 years. Melena was the most frequent UGIB presentation (70%). Forty-five percent had associated diseases, and 45% were taking gastroerosive drugs. Duodenal ulcer was the most frequent cause of UGIB (48%), followed by gastric ulcer (32%). The evolution of UGIB was unfavorable in 7% of cases. Variables associated with unfavorable evolution in the multivariate analysis were: systolic blood pressure < or = 100 mm Hg, heart rate > or = 100 bpm, and a Forrest endoscopic classification of severe. Only 10% of patients were immediately discharged, with no subsequent complications. However, if predictive variables obtained in the multivariate analysis had been used, hospitalization could have been prevented in 115 patients (34%) without subsequent complications. A number of clinical and endoscopic variables (blood pressure, heart rate, and endoscopic stigmata of bleeding) with prognostic value have been identified. These are easy to obtain and apply in clinical practice and allow an accurate estimation of the evolution of UGIB. This diagnostic strategy identifies a relatively high proportion of UGIB patients who can be managed on an outpatient basis.

Association of the Predominant Symptom With Clinical Characteristics and Pathophysiological Mechanisms in Functional Dyspepsia

Functional dyspepsia (FD) is considered a heterogeneous disorder with different pathophysiological mechanisms contributing to the symptom pattern. The Rome II committee proposed that subdividing patients with FD into groups with predominant pain versus discomfort might identify subgroups with homogeneous pathophysiological and clinical properties. The aim of this study was to analyze the relationship of predominant pain or discomfort with pathophysiological mechanisms and to evaluate whether considering individual predominant symptoms yields better results. Consecutive FD patients (n = 720; 489 women; mean age, 41.3 +/- 0.6 years) filled out a dyspepsia questionnaire and identified a single most bothersome symptom. We analyzed the association of this predominant symptom with demographic, clinical, and pathophysiological features (Helicobacter pylori status, gastric emptying in 592 patients, and gastric sensitivity and accommodation testing in 332 patients). According to Rome II criteria, 22% were pain predominant and 78% discomfort predominant. Patients with predominant pain had a higher prevalence of hypersensitivity (44% vs 25%) and delayed gastric emptying was observed less frequently in these patients (16% vs 26%), but there was major overlap. Detailed analysis showed that any of 8 dyspeptic symptoms could be predominant. Predominant early satiety or vomiting was associated with significantly higher prevalences of weight loss (89% and 75%, respectively) and of acute onset (61% and 60%, respectively). Impaired accommodation was found in 79% of patients with predominant early satiety. The highest prevalence of delayed emptying was found in predominant fullness (38%) and of hypersensitivity in predominant pain (44%). Subdividing FD patient groups according to the predominant symptom does not reliably identify subgroups with a homogeneous underlying pathophysiological mechanism.

Diffuse gastroduodenitis and pouchitis associated with ulcerative colitis

We experienced a very rare case of ulcerative colitis (UC) accompanied with analogous lesions in the stomach, duodenum, and ileal J-pouch. Ileal J-pouch anal anastomosis was performed on a 29-year old woman in 1996. Six years later, she was admitted again to our hospital because of epigastralgia, nausea, watery diarrhea and low fever. Based on the results of endoscopic examination, we diagnosed it as pouchitis. Moreover, on hypotonic duodenography, expansion of the duodenal bulb and the descending portion were poor. Kerckring folds disappeared with typical lead-pipe appearance. The pathogenesis of the gastric and duodenal lesion in this patient was similar to that of the colonic lesions of UC. For the gastroduodenal lesions in this patient, symptomatic remission was obtained following administration of crushed mesalazine tablets (1500 mg/d) for 14 d with continuous administration of omeprazole. Firstly we used ciprofloxacin to treat pouchitis. On the fifth day, she got a fever because of catheter infection. In the catheter culture, methicillin-resistant Staphylococcus aureus (MRSA) was detected. Therefore we changed ciprofloxacin to vancomycin hydrochloride (Vancomycin). Vancomycin was very effective, and the stool frequency dramatically improved in three days. Now she continues to take mesalazine, but her condition is stable and there has been no recurrence of pouchitis.

Bromophenacyl bromide, a phospholipase A2inhibitor attenuates chemically induced gastroduodenal ulcers in rats

To study the effect of bromophenacyl bromide (BPB), a phospholipase A2 inhibitor on gastric secretion and to protect chemically induced gastric and duodenal ulcers in rats. Acid secretion studies were undertaken in pylorus-ligated rats with BPB treatment (0, 5, 15 and 45 mg/kg). Gastric and duodenal lesions in the rats were induced by ethanol and cysteamine respectively. The levels of gastric wall mucus, nonprotein sulfhydryls (NP-SH) and myeloperoxidase (MPO) were also measured in the glandular stomach of rats following ethanol induced gastric lesions. BPB produced a dose-dependent inhibition of gastric acid secretion and acidity in rats. Pretreatment with BPB significantly attenuated the formation of ethanol induced gastric lesion. BPB also protected intestinal mucosa against cysteamine-induced duodenal ulcers. The antiulcer activity of BPB was associated with significant inhibition of ethanol-induced depletion of gastric wall mucus, NP-SH and MPO. These findings pointed towards the mediation of sulfhydryls in BPB induced gastrointestinal cytoprotection. BPB possesses significant antiulcer and cytoprotective activity against experimentally induced gastroduodenal lesions.

Mechanisms of protection by pantoprazole against NSAID-induced gastric mucosal damage

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) can be associated with severe adverse digestive effects. In clinical settings, proton pump inhibitors have proven to be effective in preventing and healing NSAID-induced gastroduodenal lesions. The present study investigates the mechanisms of protection afforded by pantoprazole against gastric injury induced by different NSAIDs in rats. Animals were orally treated with indomethacin (100 micromol/kg), diclofenac (60 micromol/kg), piroxicam (150 micromol/kg) or ketoprofen (150 micromol/kg). Thirty minutes before NSAIDs, animals received pantoprazole 6 or 60 micromol/kg orally. Four hours after NSAIDs, the following parameters were assessed: histomorphometric evaluation of gastric mucosal damage; gastric mucosal levels of myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione as an index of non-proteic sulfhydryl compounds (GSH), and prostaglandin E2 (PGE2); mucosal cyclooxygenase-1 and -2 (COX-1, COX-2) mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). Separate experiments were carried out to assay the effects of pantoprazole on gastric acid secretion in pylorus-ligated rats. The in vitro influence of pantoprazole (1-10 microM) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate was also examined. All NSAIDs elicited mucosal necrotic lesions associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels, were detected in the gastric mucosa of indomethacin-, piroxicam- or ketoprofen-treated animals. Indomethacin enhanced mucosal COX-2 expression, while not affecting COX-1. At the oral dose of 6 micromol/kg pantoprazole did not affect NSAID-induced mucosal damage, whereas at 60 micromol/kg it markedly reduced injuries provoked by all test NSAIDs. Pantoprazole 60 micromol/kg also reversed the effects of NSAIDs on MPO, MDA, and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced COX-2 expression. However, at both doses, pantoprazole inhibited acid secretion in pylorus-ligated rats. Furthermore, pantoprazole concentration dependently reduced the in vitro oxidation of LDLs. Our results suggest that besides inhibiting acid secretion, the protection afforded by pantoprazole against NSAID-induced gastric damage depends on a reduction in mucosal oxidative injury, which may also account for an increment of sulfhydryl radical mucosal bioavailability. It is also suggested that pantoprazole does not influence the down-regulation of gastric prostaglandin production associated with NSAID treatment.

Mucosal proinflammatory cytokine and chemokine expression of gastroduodenal lesions in Crohn's disease

The stomach and the duodenum are frequent sites of involvement by diminutive lesions in Crohn's disease (CD). To assess mucosal proinflammatory cytokines and chemokines in gastroduodenal lesions of CD. 13C-Urea breath test and upper endoscopy were performed in 29 CD patients and seven control subjects, and biopsy specimens were obtained from the gastric cardia and the duodenum. Histology and mucosal levels of IL-1beta, IL-8/CXCL8 and RANTES/CCL5 were assessed and compared according to the presence of gastric cardial lesion [bamboo joint-like appearance (BJA)] and duodenal lesion (notched appearance, aphthous erosion and polypoid lesion). In 11 CD patients, these procedures were repeatedly performed after administration of famotidine. H. pylori was less frequently positive in CD patients than in controls (10% vs. 71%, P = 0.003). Prevalence of cardial and duodenal lesion was significantly higher in CD than in controls (59% vs. 0%, P = 0.008 for gastric lesion; 45% vs. 0%, P = 0.034 for duodenal lesion). There were no differences in IL-1beta, IL-8 and RANTES between CD and controls. Duodenal mucosal IL-1beta and IL-8 were significantly higher in positive duodenal lesion than in negative duodenal lesion. However, there were no such differences with respect to cardial lesions. Endoscopic findings remained unchanged after administration of famotidine, while there was a trend towards decreases in IL-1beta and IL-8 in the gastric cardia. The pathogenesis of diminutive lesions of CD may be different between the stomach and the duodenum. Famotidine may not have a therapeutic effect on duodenal lesion in CD.

Gastro-Duodenal Dieulafoy's Lesion: Early, Intermediate and Late Outcomes

Gastro-Duodenal Dieulafoy's Lesion: Early, Intermediate and Late Outcomes

Superiority of the gastroduodenal safety profile of licofelone over rofecoxib, a COX‐2 selective inhibitor, in dogs

This study assessed the gastroduodenal safety profile of licofelone, a new nonsteroidal anti-inflammatory drug with dual inhibitory activity against 5-lipoxygenase and cyclo-oxygenase (COX), by using endoscopic evaluations and by comparing licofelone to rofecoxib, a selective COX-2 inhibitor. Twenty-one dogs underwent blinded gastroduodenoscopies, during which the mucosa of the gastroduodenal tract was assessed and scored. Blood analyses were monitored on days 0 (baseline), 14, 28, 42, and 56. Examinations to detect fecal occult blood were performed daily. Dogs were randomly assigned to three groups that received either a placebo, licofelone at a dose of 2.5 mg/kg twice daily, or rofecoxib at a dose of 0.5 mg/kg daily, respectively. Significant differences between the groups in gastric (P = 0.003), duodenal (P = 0.009), and gastroduodenal (P = 0.002) endoscopic lesion scores were observed at day 56. Rofecoxib-treated dogs had more lesions in all areas when compared with placebo-treated dogs, more duodenal lesions when compared with licofelone-treated dogs and more lesions than they had at baseline. In contrast to licofelone, rofecoxib was found to induce significant gastric and gastroduodenal lesions in dogs that lacked pre-existing lesions at baseline. Blood analyses and fecal examinations did not reveal abnormalities in any of the experimental groups. Treatment with licofelone was well tolerated and was shown to be safer than rofecoxib in terms of upper gastrointestinal damage. In this way, this study demonstrates the gastroduodenal safety profile of licofelone for chronic treatment.

Helicobacter pylori infection and the prevention of peptic ulcer with proton pump inhibitors in elderly subjects taking low-dose aspirin

Introduction. The role of Helicobacter pylori infection on the risk of low-dose aspirin-related gastroduodenal damage and on the efficacy of the prevention therapy in elderly chronic users of low-dose aspirin is still controversial. Aim. To evaluate in symptomatic elderly chronic users of low-dose aspirin: (1) the association between H. pylori infection and the prevalence of upper gastrointestinal lesions; and (2) the effect of H. pylori infection on the efficacy of proton pump inhibitors in the prevention of aspirin-related gastroduodenal lesions. Patients and methods. Two hundred and forty-five symptomatic elderly who were taking aspirin 75–300 mg daily, at least during the last 3 months, were evaluated by endoscopy. A structured interview was carried out to evaluate gastrointestinal symptoms and the use of proton pump inhibitors. H. pylori infection was diagnosed according to histology and the rapid urease test on gastric biopsies. Results. One hundred and twelve patients were H. pylori-positive and 133 patients were H. pylori-negative. A significantly higher prevalence of peptic ulcers was observed in H. pylori-positive than in H. pylori-negative subjects (36.6% versus 15.8%, P = 0.0002). The use of proton pump inhibitors was associated with a significant decreased risk of peptic ulcer both in H. pylori-positive (absolute risk reduction, ARR = −36.2, 95% confidence interval: −51.2 to −21.3, P < 0.001) and H. pylori-negative patients (ARR = −12.6, 95% confidence interval: −23.9 to −1.2, P = 0.03). However, the number of patients who needed to be treated in order to gain a reduction of one peptic ulcer (number needed to treat, NnT) was lower in H. pylori-positive than in H. pylori-negative patients (NnT = 3 versus 8). Conclusions. In symptomatic elderly chronic users of low-dose aspirin, H. pylori infection may influence the prevalence of peptic ulcers and the cost-effectiveness of the proton pump inhibitor prevention therapy.

Evaluation of gastroduodenal mucosal lesions in patients with Crohn's disease and ulcerative colitis

Background: Patients with Crohn's disease (CD) are reported to suffer from upper gastroduodenal lesions with varying frequency, although concurrent Helicobacter pylori infection is reported to be low.Methods: A prospective study was carried out on patients diagnosed with CD or ulcerative colitis (UC) in order to evaluate the degree of upper gastroduodenal tract involvement and the prevalence of Helicobacter pylori infection.Results: Gastroduodenal lesions were found in 18 (78%) of 23 CD patients, the location being the stomach in 18 (78%), the duodenal bulb in 16 (70%) and the descending duodenum in 16 (70%). Bamboo joint‐like lesions were found in four cases (17%) in gastric body and cardia. In contrast, gastroduodenal lesions were found in 10 (53%) of 19 UC patients, the location being the stomach in nine (47%), the duodenal bulb in six (32%), and the descending duodenum in three (16%). The H. pylori‐positive rate in patients with CD and UC was 0%, and 11%, respectively.Conclusion: Minute upper gastroduodenal lesions are much more common in CD than in UC patients, especially in the descending duodenum. Accordingly, upper gastrointestinal endoscopy would seem to be a useful means with which to obtain a definitive diagnosis in all suspected IBD cases.

Traitements curatif et préventif des ulcères gastro-duodénaux induits par les AINS

The use of treatments to heal or to prevent nonsteroidal anti-inflammatory drugs (NSAIDs) associated gastroduodenal lesions is based on replacement of mucosal prostaglandin deficiency or inhibition of acid secretion. Four-week acid suppression by proton pump inhibitors (PPI) with 7-day eradication triple therapy in Helicobacter pylori positive patients is effective in healing gastric and duodenal ulcer upon discontinuation of NSAIDs. In the event NSAIDs must be continued, PPIs (omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg) are more effective than H2-blockers and cytoprotective agents (sucralfate, misoprostol) to heal mucosal lesions. In long-term prevention studies, omeprazole 20 mg, lansoprazole 15 mg, and pantoprazole 20 mg significantly reduce gastric and duodenal ulcer rates. Misoprostol 800 microg is as effective as PPIs for preventing symptomatic and complicated gastric ulcers, but less effective to prevent duodenal ulcer, with a high rate of adverse effects such as diarrhea. Helicobacter pylori eradication in infected patients decrease the risk of NSAIDs-associated lesions but is less effective than concomitant antisecretory treatment. Current data from comparative studies of PPIs vs ranitidine or misoprostol are in favor of the PPIs as well tolerated and effective drugs in the prophylaxis of NSAIDs-related gastroduodenal lesions in high-risk patients.

Physiopathologie des lésions gastro-duodénales induites par les anti-inflammatoires non stéroïdiens

The pathogenesis of the gastroduodenal lesions induced by non-steroidal anti-inflammatory drugs and aspirin is primarily caused by a reduction in mucosal blood flow, which is the consequence of inhibition of cyclooxygenase-producing vasodilator prostaglandins. The subsequent phase is adherence of leukocytes to the endothelium, which may depend on cyclooxygenase-2. Endothelial lesions accentuate the fall of mucosal blood flow and promote the inflammatory process in the gastric mucosa. The inflammatory process is amplified by expression of TNFalpha in polymorphonuclears induced by non-steroidal anti-inflammatory drugs. A few days after starting treatment, epithelial proliferation and increased mucosal blood flow, partly dependent on cyclooxygenase-2 and nitric oxide expression, compensates for the damaging process. Selective inhibitors of inducible cyclooxygenase-2 have reduced gastrointestinal toxicity, which could partially be explained by the protection effect of cyclooxygenase-2 on the gastrointestinal mucosa during inflammation or epithelial repair. Selective inhibitors may worsen inflammatory bowel disease. Non-steroidal inflammatory drugs and aspirin, but perhaps not selective inhibitors, increase the mucosal lesions associated with Helicobacter pylori-induced gastritis. Co-administration of selective inhibitors and aspirin leads to gastrointestinal toxicity equivalent to that of non-specific anti-inflammatory drugs.

Low prevalence of Helicobacter pylori but high prevalence of cytomegalovirus‐associated peptic ulcer disease in AIDS patients: Comparative study of symptomatic subjects evaluated by endoscopy and CD4 counts

The role of Helicobacter pylori infection in gastroduodenal lesions might be different between the general population and AIDS patients. The aim of the present study was to compare the prevalence of H. pylori and cytomegalovirus (CMV) infection in AIDS patients and HIV-negative controls. The impact of CD4 lymphocyte counts on H. pylori and CMV infection in the same subjects was also assessed. One hundred and fifty-six patients (52 HIV-positive, 104 HIV-negative) with gastrointestinal symptoms were evaluated with upper gastrointestinal endoscopy and biopsy. Comparison of the prevalence of H. pylori and CMV infection was made by dividing AIDS patients into two groups: those with CD4 counts >100/mm3 and those with CD4 counts <100/mm3, and ulcer and non-ulcer patients. In comparison with HIV-negative controls, AIDS patients had a lower prevalence of H. pylori infection (P < 0.0001) but a higher prevalence of CMV infection (P < 0.0001). Cytomegalovirus infection was frequently found in AIDS patients with CD4 count <100/mm3, in comparison with those with a CD4 count >100/mm3. In AIDS patients, CMV was more frequently detected in subjects with peptic ulcers (P = 0.0125). Conversely, the prevalence of H. pylori infection in AIDS patients was not different between those with and without peptic ulcers. The low prevalence of H. pylori infection and peptic ulcer in AIDS patients suggests a different role of H. pylori infection in peptic ulcer or even a different mechanism of peptic ulcerogenesis in HIV-positive subjects. Cytomegalovirus, rather than H. pylori, may be the main causative pathogen of peptic ulcers in AIDS patients.

Changes in Helicobacter pylori status in patients with rheumatoid arthritis under non‐steroidal anti‐inflammatory drugs

Background: The role of Helicobacter pylori infection in rheumatoid arthritis (RA) patients during treatment with non‐steroidal anti‐inflammatory drugs (NSAID) is still unclear. Methods: By means of endoscopy and biopsy, gastroduodenal lesions and H. pylori status were repeatedly examined in 88 RA patients at intervals ranging from 26 to 49 months. Histology and culture were applied to determine H. pylori status. Serial changes in gastroduodenal lesions and histologic score for mucosal atrophy were compared among groups classified by initial and second H. pylori status. Results: There were 28 patients with continuously positive H. pylori infection (CP group), 33 patients with continuously negative H. pylori infection (CN group), 7 patients in whom H. pylori status became negative (PN group), and 20 patients in whom H. pylori status could not be determined (UD group). Age, duration and species of NSAID, disease activity of RA, gastroprotective drugs applied and the prevalence of gastroduodenal mucosal lesions were not different among the groups at either the initial or the second examination. In the PN group, the score for mucosal atrophy at the second examination was significantly lower than at the initial examination, whereas no difference was found for the CP, CN and UD groups. Overall, histologic score for mucosal atrophy was higher in H. pylori‐positive patients than in H. pylori‐negative patients at both initial and second examination. Conclusions: In RA patients using NSAIDs, H. pylori infection may not affect the course of gastroduodenal lesions and activity of RA, but the infection contributes to mucosal atrophy.

Helicobacter pylori diagnosis in patients with liver cirrhosis.

In cirrhotics, Helicobacter pylori infection is the major cause of peptic lesions, which are an important cause of upper intestinal haemorrhage in these patients. However, some diagnostic methods are not accurate for H. pylori detection in cirrhotics. The study assessed the accuracy of different diagnostic methods for H. pylori detection in cirrhotics with and without gastroduodenal lesions. The study population comprised of 53 cirrhotics. All patients underwent upper endoscopy: three biopsies were taken in the antrum and three in the gastric body. Four biopsies were used for Giemsa staining, while two were used for a rapid urease test. A blood sample was obtained for serology using Western blotting, and a [13C]urea breath test was performed in all patients. Histological assessment was regarded as the gold standard for diagnosis of H. pylori infection. H. pylori infection was detected at histological assessment in 28 (52.8%) patients. The [13C]urea breath test, rapid urease test, and serology were positive in 27 (51%) patients, 23 (43.4%) patients, and 34 (64.1%) patients, respectively. Sensitivity and specificity were 92.9 and 96% for the [13C]urea breath test, 78.6 and 96% for the rapid urease test, and 78.6 and 52% for serology. The [13C]urea breath test is very accurate in cirrhotics, whilst both serology and the rapid urease test give disappointing results.

Endoscopic findings in end-stage renal disease.

Patients with end-stage renal disease (ESRD) may demonstrate a number of gastrointestinal lesions and suffer subsequent complications. Our aim was to investigate the endoscopic findings in these patients and identify the predisposing factors. During a 1-year period (February 2000 to January 2001), we studied consecutive patients with end-stage renal disease who were undergoing routine endoscopy before renal transplantation. The rapid urease test was also performed to detect Helicobacter pylori infection. Demographic and clinical data were collected. Logistic regression analysis was used to determine the risk factors for important endoscopic lesions, including esophagitis, gastroduodenal erosions, and peptic ulcers. We studied 206 patients (124 male, 82 female, mean age 38.9). Of the patients 73.8% were asymptomatic but some patients experienced nausea (12.6%), heartburn (8.7%), and abdominal pain (7.3%). Endoscopy was normal in 74 patients (35.9%). Abnormal endoscopic findings were duodenal erosions (32.0%), antral erosions (22.8%), diffuse antral erythema (27.8%), duodenal ulcer (7.3%), esophagitis (5.8%), angiodysplasia (4.4%), nodular duodenum (2%), and inflammatory gastric polyps (1.5%). The rapid urease test was positive in 58.8% of patients. Important endoscopic lesions were more common in men and in H. pylori-infected patients. Age, duration of dialysis, cause of the ESRD, presence of any symptoms, and hemoglobin levels were not found to be related to these lesions. Most patients with peptic ulcers were asymptomatic. Duodenal erosions (32.0%), gastric erosions (22.8%), diffuse antral erythema (27.8%) and duodenal ulcer (7.3%) are common lesions in patients with end-stage renal disease. Male gender and H. pylori infection are associated with a higher risk of these lesions. As there is no association between patients' symptoms and gastroduodenal lesions, which may increase the risk of post-transplant complications, the development of diagnostic strategies for the detection of these lesions is recommended.

Margem de segurança do meloxicam em cães: efeitos deletérios nas células sangüíneas e trato gastrintestinal

Este trabalho investigou a margem de segurança do inibidor COX-2, meloxicam, em cães, enfocando seus efeitos deletérios nas células sangüíneas e no trato gastrintestinal. Para tanto, após uma avaliação clínico-laboratorial, os cães foram distribuídos nos seguintes grupos: I (placebo; n= 3), II (piroxicam; 1,0mg kg-1; n= 5), III (meloxicam; 0,2mg kg-1; n= 5), IV (meloxicam;1,0mg kg-1; n= 5) e V (meloxicam; 2,0mg kg-1; n= 5). Os fármacos foram usados, por via oral, por 16 dias. No 17º dia, repetiu-se o hemograma completo e, então, procedeu-se a eutanásia seguida pela necrópsia. No grupo I, não houve alterações dignas de nota. No grupo II, todos os cães apresentaram episódios moderados de vômito e diarréia. O perfil celular sangüíneo não foi significativamente modificado. Em dois cães, houve redução no hematócrito e na hemoglobina. Na necropsia, observaram-se focos hemorrágicos e lesões gastriduodenais moderadas. A análise microscópica revelou a presença de gastrite e enterite ulcerativa. No grupo III, quatro cães (80%) apresentaram vômito e diarréia, sem alteração no perfil celular sangüíneo. Na análise macroscópica, observaram-se lesões brandas na mucosa gástrica e focos hemorrágicos no duodeno em quatro cães. Na histopatologia, observaram-se lesões sugestivas de discreta gastroenterite. No grupo IV, os cinco cães tiveram vômito e diarréia sanguinolenta. Quatro deles (80%) apresentaram anemia (p &lt; 0,05). Quatro e cinco cães apresentaram redução no hematócrito e hemoglobina, respectivamente. Ocorreram, ainda, leucocitose, neutrofilia e linfopenia significantes (p &lt; 0,05), em 60% dos cães. Na necrópsia, evidenciaram-se hiperemia, hemorragia e úlceras gástricas severas em 100% dos animais. Verificou-se na microscopia um quadro de gastroenterite ulcerativa nos cinco cães. No grupo V, todos os cães apresentaram sérios episódios de vômito, diarréia e melena. Os quatro (80%) cães que suportaram o tratamento apresentaram anemia e leucocitose com neutrofilia e linfopenia significativas (p&lt; 0,05). Houve, ainda, uma redução no hematócrito e hemoglobina desses cães. Na necropsia, foram visualizadas hemorragias e graves ulcerações gastroduodenais. À histopatologia, evidenciou-se severa gastroenterite. Conclui-se que o meloxicam, mesmo sendo COX-2 seletivo, induz efeitos deletérios no trato gastrintestinal e células sangüíneas de cães, quando administrado em concentrações cinco e dez vezes a dose terapêutica, que demonstram sua estreita margem de segurança nesta espécie.

Gastrointestinal safety of NO-aspirin (NCX-4016) in healthy human volunteers: A proof of concept endoscopic study

Background & Aims: NCX-4016 is a nitric oxide–releasing derivative of aspirin with antiplatelet activity. The aim of this study was to investigate the effect of NCX-4016 on gastrointestinal mucosa and platelet functions in healthy human volunteers. Methods: This was a parallel-group, double-blind, placebo-controlled study. Forty healthy subjects were randomly allocated to receive 7 days of treatment with NCX-4016 (400 and 800 mg twice daily), equimolar doses of aspirin (200 and 420 mg twice daily), or placebo. Upper endoscopies were performed before and at the end of the treatment period, and gastroduodenal lesions were graded using a predefined scoring system. Basal and posttreatment platelet aggregation in response to arachidonic acid (AA) and serum thromboxane (TX) B2 and AA-stimulated platelet TXB2 production were investigated. Results: Mucosal endoscopic injury score on day 7 was 0.63 ± 0.16 in the placebo group and 11.0 ± 3.0 and 16.1 ± 1.6 in healthy volunteers treated with 200 and 420 mg aspirin twice daily (P < 0.0001 vs. placebo). NCX-4016 was virtually devoid of gastric and duodenal toxicity, resulting in a total gastric and duodenal endoscopic score of 1.38 ± 0.3 and 1.25 ± 0.5 (P < 0.0001 vs. aspirin, not significant vs. placebo). NCX-4016 inhibited AA-induced platelet aggregation as well as serum TXB2 and platelet TXB2 generation induced by AA to the same extent as aspirin (not significant vs. aspirin). Conclusions: In this study, we have proven the concept that addition of an NO-donating moiety to aspirin results in a new chemical entity that maintains cyclooxygenase-1 and platelet inhibitory activity while nearly avoiding gastrointestinal damage.GASTROENTEROLOGY 2003;124:600-607

Helicobacter pylori infection in patients with liver cirrhosis: facts and fictions.

Helicobacter pylori infection could play a role in different clinical alterations observed in cirrhosis, from gastroduodenal lesions to hepatic encephalopathy. Although its prevalence in cirrhotics is similar to that in controls, H. pylori infection is responsible for the increased prevalence of peptic ulcer observed in these patients. The ammonia production by H. pylori urease does not seem to increase blood ammonia levels during cirrhosis, indicating that its role in hepatic encephalopathy could be marginalized in clinical practice. Dual and triple therapies have been shown to be equally effective for H. pylori eradication in these patients.