bluuebunny/crossref_metadata_2025 huggingface dataset:
Triple Therapy with Omeprazole, Amoxicillin and Clarithromycin Is Effective against Helicobacter Pylori Infection in Gastric Ulcer Patients as well as in Duodenal Ulcer Patients
Authors: Habu Yasuki , Mizuno Shigeto , Hirano Seiichi , Kiyota Keisuke , Inokuchi Hideto , Kimoto Kunihiko , Nakajima Masatsugu , Kawai Keiichi
Published: April 2003

Background/Aims: There have been few reliable published studies permitting assessment of therapeutic regimens for Helicobacter pylori infection in gastric ulcer (GU) patients. The aim of the present study was to evaluate the efficacy of omeprazole-based dual and triple therapy regimens, both including clarithromycin, for the cure of H. pylori infection in active GU and duodenal ulcer (DU) patients. The study was conducted in Japan, a country in which GU is more prevalent than DU. Methods: Two hundred and thirty-four consecutive peptic ulcer patients (GU: n = 124; DU: n = 103; GDU: n = 7) suffering from H. pylori infection were randomly treated with either omeprazole 20 mg b.i.d. + amoxicillin 500 mg q.i.d. + clarithromycin 400 mg b.i.d. (OAC) or with omeprazole 20 mg b.i.d. + clarithromycin 400 mg b.i.d. (OC) for 14 days. H. pylori infection was evaluated by histology and culture from antral and corpus biopsies 6 weeks after completing antimicrobial therapy. Results: Follow-up data were available in 202 patients. The cure rates of H. pylori infection in GU patients were 83.9% (47/56) with OAC and 59.2% (29/49) with OC. Corresponding rates in DU patients were 91.5% (43/47) and 70.5% (31/44), respectively. The cure rates with OAC were significantly higher than those with OC (p < 0.001, χ2 test). The cure rates in GU patients were lower than those in DU patients for both regimens, but these differences were not statistically significant. Side effects were generally mild and did not interfere with compliance. One patient in the OAC group and 2 patients in the OC group complained of severe side effects that led to therapy discontinuation. Conclusions: Triple therapy with omeprazole, amoxicillin and clarithromycin is a safe and effective regimen for the cure of H. pylori infection in GU patients as well as in DU patients. We recommend this triple regimen as a first-line treatment in all patients with peptic ulcers associated with H. pylori infection in Japan.
Monitor Peptide (Rat Pancreatic Secretory Trypsin Inhibitor) Directly Stimulates the Proliferation of the Nontransformed Intestinal Epithelial Cell Line, IEC-6
Authors: Fukuda Masako , Fujiyama Yoshihide , Sasaki Masaya , Andoh Akira , Bamba Tadao , Fushiki Tohru
Published: April 2003

Background/Aims: The growth-stimulating activity of monitor peptide [rat pancreatic secretory trypsin inhibitor (PSTI)-61] was evaluated in the rat intestinal epithelial cell line IEC-6. In response to food intake, monitor peptide induces cholecystokinin release and the subsequent secretion of pancreatic enzyme into the rat small intestine. Methods: Monitor peptide was purified from rat bile-pancreatic juice. The proliferation of IEC-6 cells was determined by both counting cell number and [3H]-thymidine incorporation. Ornithine decarboxylase (ODC) activity was assessed by radiometric technique using L-[1-14C]-ornithine. Results: Monitor peptide (102–105 ng/ml) induced a significant increase in the incorporation of [3H]-thymidine into IEC-6 cells, and this effect was observed in a dose-dependent manner. A significant increase in the cell number was also observed. An antibody specific for the synthetic NH2-terminal fragment of monitor peptide completely abrogated the growth-stimulating effects of this peptide. In addition, monitor peptide effectively increased the ODC activity of IEC-6 cells. Conclusions: These results indicate that monitor peptide stimulates the growth of intestinal epithelial cells, and suggest that polyamine metabolism may be involved in this mechanism of growth induction.
Treatment of Peptic Ulcer
Authors: Tytgat Guido N.J.
Published: April 2003

The current therapy of choice for all Helicobacter pylori-associated ulcer disease is eradication therapy. Although adequate therapeutic regimens are currently available, often still ineffective therapies are tried. Cure of the infection essentially eliminates the ulcer diathesis. Cure of the infection is especially indicated in complicated/recalcitrant ulcer disease. Sadly, at present only a minority of peptic ulcer disease patients receive adequate eradication therapy. Cure of the infection does not equal full resolution of dyspeptic symptoms. A variable percentage of patients continues acid suppressant therapy for ongoing or newly developed dyspeptic or reflux symptoms. Acid-suppressant therapy, both for healing and for maintenance, remains the cornerstone of peptic ulcer therapy in all other circumstances (H. pylori-negative ulcer, aspirin/NSAID-induced ulceration, hyperacidity related ulcer etc.). Proton pump inhibitors are superior to H2RAS both for healing and for maintenance. Whether higher doses are occasionally necessary in H. pylori-negative ulcers, requires further study. Acid-suppressant therapy, even when prolonged, so far appears safe and well tolerated.
Malabsorption Syndromes
Authors: Bai Julio C.
Published: April 2003

Background/Aims: Malabsorption syndromes commonly result from a pathological interference of the normal digestive process. There have been major advances in the last 4 years. The purpose of this review is to highlight in the form of a brief summary the most outstanding information available. Methods: The review was performed based on a medical literature search using MEDLINE (1993–1997), bibliographic reviews of book chapters and review articles. As a consequence of the extensive information incorporated in the period and the limited scope of this review, the review will focus in three aspects: (1) an overview on some clinical aspects of malabsorption; (2) diseases in which predominates the disturbed mucosal phase of the digestive process, and (3) providing information on diagnostic testing regarding malabsorption. Results: Major advances on celiac disease, Whipple’s disease, giardiasis, tropical sprue, malabsorption of oligo- and disaccharides, vitamin B12 and bile salts are discussed. New aspects on diagnostic procedures for malabsorption are also presented. Conclusion: Although major advances have given a great support to the investigation of malabsorption, yet the syndrome remains a major diagnostic dilemma. Based on the limited availability of most diagnostic tests, a simple and practical diagnostic algorithm is presented.
Medical Treatment of Portal Hypertension
Authors: Bosch Jaime
Published: April 2003

The medical treatment of portal hypertension has experienced marked progress in the past decade due to the production of effective portal hypertension therapy. This has been possible because of the better understanding of the pathophysiological mechanisms leading to portal hypertension. A major step forward was the introduction of beta-blockers for the prevention of bleeding and rebleeding from gastroesophageal varices. Effective therapy requires the reduction of the hepatic venous pressure gradient (HVPG) to 12 mm Hg or below, or at least by 20% of baseline values. Unfortunately, this is only achieved in 1/3–1/2 of patients. The combination therapy associated with isosorbide-5-mononitrate and propranolol or nadolol administration enhances the fall in portal pressure and increases the number of patients in whom HVPG decreases more than 20% and below 12 mm Hg. Randomized trials (RCTs) support the fact that combination therapy is more effective than propranolol or nadolol alone and better than sclerotherapy. In the treatment of acute variceal bleeding, pharmalogical therapy offers the unique advantage of permitting the provision of specific therapy immediately after arrival to hospital, or even during transferral to hospital by ambulance, since it does not require sophisticated personnel. Terlipressin has proved to be effective and to decrease mortality from bleeding. RCTs have shown that this drug is as effective and safer than emergency sclerotherapy. Therapy should be maintained for five days to prevent early rebleeding. Somatostatin is probably as effective as terlipressin.
Medical Therapy of Achalasia: A Benefit Reserved for Few
Authors: Bortolotti M.
Published: April 2003

Background: The rationale for medical therapy of initial achalasia and the results obtained over the last 20 years in our laboratory are presented. Methods: Achalasic patients were selected as candidates for medical therapy on the basis of the presence of a slight esophageal dilation (<5 cm) on X-rays and a good manometric response to nifedipine administration. These patients were asked to take 10–20 mg of nifedipine sublingually 30–45 min before each meal for 2 weeks. Chronic medical therapy was continued only in those with an ‘excellent’ or ‘good’ clinical response to nifedipine and a lack of severe side effects. X-ray controls were planned every 6 months and manometric examination after the first 6 months. Results: Of the 56 patients selected in the above-mentioned manner, 17 had an insufficient clinical response or severe side effects during the initial trial and did not continue medical therapy. Of the 39 patients who started chronic medical treatment, 13 are still on therapy and 26 stopped after an average of 2.8 years: 17 because they underwent dilation or myotomy; 4 for unknown reasons, and 5 apparently recovered. Esophageal manometry was carried out in 4 of the latter patients and revealed that the achalasic motor pattern had been replaced by a near-normal pattern. Conclusions: We believe that medical treatment of achalasia should be carried out not only in those patients who cannot undergo invasive procedures or do not respond well to them, but also in patients with initial achalasia selected using the above-mentioned criteria, because regression of the disease could take place in some of them.
Release of Hyaluronan and Laminin into Pancreatic Secretions
Authors: Löhr M. , Fischer B. , Weber H. , Emmrich J. , Nizze H. , Liebe S. , Klöppel G.
Published: April 2003

Background: Development of fibrosis characterizes chronic pancreatitis. As it results from deposition of extracellular matrix (ECM) proteins such as hyaluronan (HA) or laminin, the release of these ECM components into blood or pancreatic secretion may be enhanced during the course of chronic pancreatitis. Patients, Material and Methods: Using immunoassays for HA and laminin, the concentration for these ECM components was measured in pancreatic juice and serum samples from 20 patients with and 20 patients without chronic pancreatitis. Pancreatic calculi of varying size and weight obtained from 13 patients with chronic pancreatitis were also examined for the content of ECM components. Tissue samples from normal pancreas and those showing chronic pancreatitis were investigated immunocytochemically with an antibody to HA synthetase (HAS). Results: After stimulation with secretin high levels of ECM components were found in the initial washout period in chronic pancreatitis patients as well as in controls. HA levels, however, were seen seven times higher in patients with chronic pancreatitis (mean ± SEM; 734 ± 301 vs. 95 ± 15 µg/l; p < 0.01). Serum HA levels correlated with the duration of chronic pancreatitis and with the levels of HA in pancreatic juice. HA and laminin were detected in the supernatants of pancreatic calculi (laminin 0.70 ± 0.30 U/l; HA 275 ± 85 µg/l). Immunocytochemically, strong staining for HAS was found in the duct epithelium and in centroacinar cells of chronic pancreatitis specimens. Conclusion: Demonstration of increased amounts of HA in pancreatic juice of chronic pancreatitis patients stimulated with secretin suggests enhanced production of this ECM component in the chronically inflamed pancreas. The source of HA appears to be the pancreatic ductal epithelium.
Pseudomembranous Colitis: Causes and Cures
Authors: Surawicz ChristinaM. , McFarland LynneV.
Published: April 2003

Clostridium difficile is the most common nosocomial pathogen of the gastrointestinal tract and has increased in frequency over time. Typical symptoms of C. difficile infection include diarrhea, which is usually nonbloody, or colitis associated with severe abdominal pain, fever and/or gross or occult blood in the stools. Pseudomembranous colitis (PMC), the severest form of this disease, occurs as a result of a severe inflammatory response to the C. difficile toxins. This review focuses on PMC, as this severe form is associated with the greatest medical concern. Diagnosis rests on detection of C. difficile in the stool, either by culture, tissue culture assay for cytotoxin B or detection of antigens in the stool by rapid enzyme immunoassays. Oral therapy with metronidazole 250 mg 4 times a day for 10 days is the recommended first-line therapy. Vancomycin is also effective, but its use must be limited to decrease the development of vancomycin-resistant organisms such as enterococci. Vancomycin (125–500 mg 4 times a day for 10 days) should be limited to those who cannot tolerate or have not responded to metronidazole, or when metronidazole use is contraindicated, as in the first trimester of pregnancy. A therapeutic response within a few days is usual. Recurrence of symptoms after antibiotics occurs in 20% of cases and is associated with persistence of C. difficile in the stools. Further recurrences then become more likely. Therapy with antibiotics in a pulsed or tapered regimen is often effective as are efforts to normalize the fecal flora. The yeast Saccharomyces boulardii has been proven in controlled trials to reduce recurrences when given as an adjunct to antibiotic therapy. Careful hand washing and environmental decontamination are necessary to prevent epidemics.
Establishment and Characterization of a Human Rectal Neuroendocrine Carcinoma Xenograft into Nude Mice
Authors: Tanaka Noritake , Onda Masahiko , Seya Tomoko , Kanazawa Yoshikazu , Naito Zenya , Asano Goro , Oguro Tatsuo
Published: April 2003

Background: Carcinoid tumor has been recognized as having a much wider spectrum than was previously thought. Now the term ‘neuroendocrine carcinoma’ (NEC) has been suggested to describe malignant epithelial tumors of neuroendocrine differentiation. Its biological behavior has not been well characterized because of the lack of in vivo models. Materials and Methods: A metastatic inguinal lymph node from rectal NEC was used for heterotransplantation into nude mice. Histochemical and immunohistochemical stainings were performed in addition to ultrastructural investigations. Hormonal peptides were measured in both xenograft tumor tissue and serum. Results: We succeeded in heterotransplantation of human rectal NEC into nude mice. To date tumorigenicity has been retained for approximately 38 months. The xenograft tumor was a histopathologically identical tumor. The immunohistochemical expression of the various hormonal peptides in the xenograft was essentially the same as that of the primary rectal tumor. Tissue and serum hormonal peptides in the xenografted tumor were measured. Serum glucagon and serotonin were significantly higher than in control mice. Conclusions: The expression of various hormonal peptides in NEC may vary depending on the surrounding environment. The establishment of NEC in xenografts provides a model for further study of the biological behavior of NEC, as well as the in vivo effects of chemotherapeutic agents on tumor growth and the release of hormonal peptides.
One-Week Triple Regime Therapy Consisting of Pantoprazole, Amoxicillin and Clarithromycin for Cure of Helicobacter pylori-Associated Upper Gastrointestinal Diseases
Authors: Dajani A.I. , Awad S. , Ukabam S. , Nounou M.A. , Rasheed Z. Abdul , Gautam S. , Aal G. Abdul , Nayal S.
Published: April 2003

This study was designed to determine the efficacy and safety of 1-week triple therapy regime consisting of pantoprazole, amoxicillin and clarithromycin in the cure of Helicobacter pylori infection leading to duodenal ulcer disease and/or gastritis. Sixty-one patients (47 males, 14 females with a mean age of 34 years) belonging to different ethnic groups suffering from H. pylori-associated duodenal ulcer and/or gastritis for an average of 2.46 years were recruited. Having satisfied primary selection criteria, patients received pantoprazole 40 mg b.i.d., clarithromycin 500 mg b.i.d. and amoxicillin 1,000 mg b.i.d. for 7 days. All medications were stopped there after H. pylori eradication was determined 4–6 weeks after treatment by a repeat endoscopy, a rapid urease test, H. pylori culture and histology assessment as indicators of cure. All three tests must be negative to consider the infection to have been successfully eradicated. Fifty-seven patients completed the efficacy analysis per protocol. Dramatic symptomatic improvement was noted in most patients immediately after stopping treatment and it was sustained at 6 weeks. At the end of the study, the healing rate of duodenal ulcers (complete re-epithelialization) following 1-week treatment only, as indicated above, and without any maintenance therapy was 66.7%, that of gastritis was 55.7%, and that of erosions was 64.3%. The overall eradication rate for H. pylori, however, was 93% (95% CI 83.0–98.1%). Furthermore, histologic evaluation revealed a remarkable resolution in the activity of gastritis in all the patients who had successful eradication of the infection.
Complex Formation among Rat Pancreatic Secretory Proteins under Mild Alkaline pH Conditions
Authors: Kleene Ralf , Kastner Berthold , Rösser Ralf , Kern Horst-Franz
Published: April 2003

Previous in vitro studies have demonstrated that enzyme proteins liberated from isolated zymogen granules of the rat pancreas aggregate already at neutral or slightly basic pH and form small particles which in the acidic pH range progressively condense into dense cores of about the size of zymogen granules. To characterize the protein composition of the original particles in more detail non-denaturing agarose gel electrophoresis was employed. Five major protein complexes were identified which upon separation of individual complexes in 1-D or 2-D gel electrophoresis were shown to be composed of a distinct set of known enzymes and several unknown proteins. Complexes 1–4 quickly dissociated when enzyme activation was induced by enterokinase, but complex 5 was resistent even to this treatment. All 5 complexes revealed a distinct fine structure when eluted from the gels and studied in negative staining electron microscopy. These findings suggest that pancreatic zymogens form complexes already in the lumen of the rough endoplasmic reticulum and are transported as such to the Golgi complex where they aggregate into granule cores due to the internal acidic pH. Complex formation may thus facilitate zymogen sorting within the rough endoplasmic reticulum and may prevent premature enzyme activation within cellular compartments.
Role of Endothelins in Trinitrobenzene Sulfonic Acid-Induced Colitis in Rats
Authors: Gulluoglu Bahadır M. , Kurtel Hızır , Gulluoglu Mine G. , Yegen Cumhur , Aktan A. Özdemir , Dizdaroglu Ferhunde , Yalin Rıfat , Yegen Berrak Ç.
Published: April 2003

To determine the role of endothelins (ET) on experimental colitis, following intracolonic trinitrobenzene sulfonic acid administration, rats were given orally either bosentan (BS), a nonselective ET receptor antagonist (100 mg/kg in 5% arabic gum), or arabic gum by gavage for 2 or 14 days. Macroscopic damage scores obtained in the vehicle (1.4 ± 0.4), acute (4.8 ± 0.6) and chronic (3.8 ± 0.3) colitis groups were significantly higher than in the control group (0). BS treatment reduced the scores in both acute (3 ± 0.5) and chronic (2.3 ± 0.5) colitis groups. Myeloperoxidase (MPO) activities of colonic tissues were elevated in acute and chronic colitis groups (325.1 ± 44.9 and 431.8 ± 54.6 U/g wet weight) as compared with the control group (73.6 ± 11 U/g wet weight). Plasma protein oxidation levels were found to be significantly increased in the chronic colitis group (1,158.1 ± 63.4 nmol/ml) compared with the control, ethanol and acute colitis groups (274.3 ± 23.1, 490 ± 52.2 and 422.2 ± 50.5 nmol/ml). BS treatment significantly reduced both the protein oxidation level (375.5 ± 46.9 nmol/ml) and MPO activity (167.5 ± 35.8 U/g wet weight). The results of the present study suggest the involvement of ETs in the pathogenesis of colonic injury in this animal model of colitis.
Primary Neuroendocrine Tumors of the Cystic Duct
Authors: Aronsky Dominik , Z’graggen Kaspar , Stauffer Edouard , Lange Jochen , Klaiber Christian
Published: April 2003

Primary neuroendocrine tumors of the cystic duct are extremely rare. Only 4 cases have been described to date. We report 2 patients in whom a primary neuroendocrine tumor of the cystic duct was incidentally detected during histological examination following cholecystectomy. With regard to the primary neuroendocrine tumor both patients were asymptomatic at the time of diagnosis. However, histologic examination did not confirm that the neuroendocrine tumors had been completely removed. Both patients underwent a second procedure. They are well after 47 and 49 months, respectively.
Localization of the Histamine H2 Receptor, a Target for Antiulcer Drugs, in Gastric Parietal Cells
Authors: Fukushima Yasushi , Ohmachi Yasushi , Asano Tomoichiro , Nawano Masao , Funaki Makoto , Anai Motonobu , Ogihara Takehide , Inukai Kouichi , Onishi Yukiko , Sakoda Hideyuki , Saitoh Toshihito , Matsuhashi Nobuyuki , Yazaki Yoshio , Sugano Kentaro
Published: April 2003

Background/Aims: Histamine H2 receptor antagonists are widely used for the treatment of peptic ulcer disorders. However, whether the H2 receptor is present in parietal or immune cells in the lamina propria remains controversial. This study is designed to determine the H2 receptor localization immunohistochemically using an antibody against the newly cloned mouse histamine H2 receptor. Methods: We cloned the mouse histamine H2 receptor gene and generated a specific antipeptide antibody against the C terminus. Immunohistochemical studies were performed with this antibody and with a monoclonal antibody against H+/K+ adenosine triphosphatase (ATPase). Results: Histamine H2 receptors were localized on the plasma membrane and on the cytoplasm just beneath the plasma membrane on the basolateral sides of gastric cells. Confocal microscopy of double-stained sections using the monoclonal antibody against H+/K+ ATPase, a specific parietal cell marker, showed that histamine H2 receptors colocalized with H+/K+ ATPase. No specific histamine H2 receptor immunoreactivities were observed in the submucosal regions. Conclusion: The H2 receptor is localized in the gastric parietal cell.
Increased Susceptibility of Diabetic Rat Gastric Mucosa to Food Deprivation during Cold Stress
Authors: Korolkiewicz Roman , Tashima Kimihito , Kubomi Masafumi , Kato Shinichi , Takeuchi Koji
Published: April 2003

Background: We investigated the mechanisms responsible for the increased susceptibility of diabetic rat gastric mucosa to damage inflicted by overnight food deprivation (18 h) and its worsening by the cold restraint stress (4°C, 3 h). Methods: Gastric damage was measured in fasted animals, some of which were rendered diabetic by a single intraperitoneal injection of streptozotocin (STZ; 70 mg/kg) 5 weeks before experiments (STZ 5W). Results: STZ 5W rodents showed a number of hemorrhagic lesions in corpus mucosa (26.8 ± 5.2 mm2) which could be prevented by insulin or nitric oxide synthase (NOS) inhibitors: aminoguanidine or L-NAME (Nω-nitro-L-arginine methyl ester). Mucosal injury was further aggravated by low temperature (51.1 ± 7.8 mm2), the damage ameliorated by insulin, aminoguanidine, or L-NAME. The salutary actions of L-NAME were L-arginine sensitive. Low temperature and L-NAME did not significantly influence the gastric secretory parameters in normal rats. On the other hand, L-NAME and aminoguanidine counteracted the attenuation of gastric juice acidity and acid output in STZ 5W rodents. Blood plasma nitrite and nitrate levels and outputs in gastric juice were augmented in STZ 5W animals in comparison to controls. The total activities of NOS including inducible NOS but not constitutive NOS were markedly enhanced by fasting and cold restraint in gastric mucosa of STZ 5W animals (2.2- and 3.7- or 2.4- and 17.9-fold respectively). Conclusions: Stressful stimuli, such as food bereavement and cold challenge contribute to the elevated susceptibility of diabetic gastric mucosa to damage, even though the main aggressive factor, i.e., gastric acid secretion, is attenuated. The enhanced production of nitric oxide by inducible NOS during food deprivation and cold exposure seems to play an important role in gastric mucosal integrity disturbances during diabetes.
Chronic Cholestasis Associated with Turner’s Syndrome
Authors: Floreani Annarosa , Molaro Mariella , Baragiotta Anna , Naccarato Remo
Published: April 2003

Liver abnormalities seem a very rare association in Turner’s syndrome, only reported in a few anecdotal cases. We report the clinical and morphological findings in 3 patients who presented with cholestasis. One of them had a definite diagnosis of primary sclerosing cholangitis, in whom the natural history was complicated by the development of two distinct tumors. A review of the few cases described in the literature and our own case reports support the hypothesis that liver disease in Turner’s syndrome may have a variety of expressions including cholestasis.
Intracellular Transport of High-Density Lipoprotein 3 in Intestinal Epithelial Cells (Caco-2) Is Tubulin Associated
Authors: Rogler Gerhard , Aschenbrenner Elisabeth , Gross Volker , Stange Eduard F. , Schölmerich Jürgen
Published: April 2003

Background: A retroendocytotic pathway for high-density lipoprotein 3 (HDL3) in cultured intestinal epithelial cell lines has been described. In small intestinal crypt cells and Caco-2, HDL3 is internalized, transported to lipid droplets and, after solubilization of these lipid droplets, resecreted. In the present study we examined the mechanisms of intracellular transport of HDL3 in the Caco-2 cell line. Methods: Apolipoprotein E free HDL3 was gold-labeled for transmission electron microscopy and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine iodide [DiI(3)] labeled for fluorescence and confocal laser scanning microscopy. For tubulin desintegration Caco-2 cells were incubated with taxol, colchicine and β- and γ-lumicolchicine. Tubulin staining was performed using a FITC labeled antibody. Uptake of HDL3 was quantified by FACS analysis. Results: HDL3 was rapidly internalized and found to be in contact with lipid droplets in the perinuclear region after 10 min. By transmission electron microscopy a frequent colocalization of HDL3-containing vesicles and tubular structures was demonstrated. The close association of HDL3-containing vesicles with fluorescence stained tubulin could be confirmed by confocal laser scanning microscopy. Preincubation of the cells with taxol and colchicine did not completely prevent internalization but reduced it during a 2-hour incubation period to less than 50% of the control cells. The transport of DiI(3)-labeled HDL3 to the lipid droplets in the perinuclear region was almost completely blocked by taxol and colchicine. Conclusion: Internalization and intracellular transport of HDL3 in intestinal epithelial cells (Caco-2) is dependent on a tubulin-mediated mechanism.
Tumor Necrosis Factor-Alpha in Ileal Mast Cells in Patients with Crohn’s Disease
Authors: Lilja I. , Gustafson-Svärd C. , Franzén L. , Sjödahl R.
Published: April 2003

Background: Reports that both intestinal and extraintestinal Crohn’s disease (CD) had healed successfully after treatment with anti-tumor necrosis factor-alpha (TNF-α) antibody have strengthened the hypothesis that it has a role in the treatment of CD. The macrophage is one source of TNF-α. Intestinal mast cells are also thought to have a role in CD, but it is not known if human ileal mast cells express TNF-α. Aim: To find out whether TNF-α is expressed by mast cells in the ileal wall in CD patients and controls. Methods: TNF-α was sought immunohistochemically in full thickness specimens of ileal wall from patients with CD (histologically normal, n = 9; inflamed, n = 6) and controls (patients with colonic cancer, n = 8). Mast cells were identified by metachromasia and anti-mast cell tryptase immunoreactivity. Results: In all layers of the ileal wall, and in every specimen investigated, mast cells were the main cell type that expressed TNF-α immunoreactivity out of the TNF-α-labelled cells. The number of TNF-α- labelled mast cells was greater in the muscularis propria in patients compared with controls, both in uninflamed (1.7-fold, p < 0.05) and in inflamed bowel (4.6-fold, p < 0.002); greater in the submucosa in inflamed compared with uninflamed CD (1.6-fold, p < 0.01), and less in the lamina propria in inflamed compared with uninflamed CD (0.4-fold, p < 0.05). Conclusion: Mast cells are an important source of TNF-α in all layers of the ileal wall, and the increased density of TNF-α-positive mast cells in the submucosa and muscularis propria may contribute to the tissue changes and symptoms in CD.
Role of Vascular Endothelial Growth Factor in Portal Hypertensive Gastropathy
Authors: Tsugawa Kouji , Hashizume Makoto , Migou Shinichirou , Kishihara Fumiaki , Kawanaka Hirofumi , Tomikawa Morimasa , Sugimachi Keizo
Published: April 2003

Background and Aims: Portal hypertensive gastropathy (PHG) is now recognized as a distinct entity; however, the angiogenesis in the portal hypertensive gastric mucosa has yet to be elucidated. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in both physiological and pathological angiogenesis. The aim of this study was thus to examine the function of VEGF in the portal hypertensive and non-portal hypertensive gastric mucosa. Method: Forty-five cirrhotic patients were divided into 3 groups as follows. Group I included 15 patients without PHG who were treated with 1.5 g teprenone/day for 8 weeks: PHG(–)-t. Group II included 15 patients with PHG who were not treated with teprenone: PHG(+)-n. Group III included 15 patients with PHG who were treated with teprenone for 8 weeks: PGH(+)-t. The gastric mucosal blood flow (GMBF), the concentration of gastric mucosal VEGF and hexosamine and the endoscopic findings were studied both before and after medication. Results: Before teprenone treatment, the GMBF in the antrum, fundus, fornix were significantly higher in PHG(+)-n than PHG(–)-t. After treatment, the GMBF in the fundus and fornix significantly decreased more than before treatment in the PHG(+)-t. After treatment, the GMBF in the antrum increased significantly more than before treatment in PHG(–)-t. The gastric VEGF and hexoxamine concentration in the antrum were significantly higher in PHG(+)-n than in PHG(–)-t. After treatment, the gastric VEGF and hexosamine concentration in the antrum significantly decreased in PHG(+)-t while no change in concentration was recognized in PHG(+)-n. In the endoscopic findings, a decrease in the PHG score was recognized in 2 patients in PHG(+)-t. Conclusion: Portal hypertensive gastric mucosal change was thus found to trigger a high concentration of VEGF and hexosamine. Such increased activity of VEGF and hexosamine may thus account for the presence of active congestion in PHG.
Pentoxifylline Accelerates Gastric Ulcer Healing in Rats: Roles of Tumor Necrosis Factor Alpha and Neutrophils during the Early Phase of Ulcer Healing
Authors: Shimizu Noriko , Watanabe Toshio , Arakawa Tetsuo , Fujiwara Yasuhiro , Higuchi Kazuhide , Kuroki Tetsuo
Published: April 2003

Background/Aims: Pentoxifylline has many anti-inflammatory properties including inhibition of production of tumor necrosis factor alpha (TNF-α). Although pentoxifylline prevents several types of gastric mucosal injury, the effect of this drug on ulcer healing is unknown. In this study, we examined the effect of pentoxifylline on healing of acetic acid induced gastric ulcers in rats. Methods: Rats with gastric ulcer received an intraperitoneal injection of 10 mg/kg pentoxifylline once daily for 14 days or for only the first 7 days or the last 7 days of the 14-day treatment period. Some rats were given antirat neutrophil antiserum intraperitoneally every other day. Ulcer size, myeloperoxidase activity, and concentration and location of TNF-α in ulcer tissue were assessed. Results: Administration of pentoxifylline for 14 days or for the first 7 days, but not for the last 7 days, of the 14-day treatment period accelerated ulcer healing. TNF-α was detected mainly in monocytes/macrophages and in some neutrophils at ulcer bases and margins. Pentoxifylline markedly decreased the concentration of TNF-α as well as the myeloperoxidase activity in ulcer tissue on days 2 and 4. Antirat neutrophil antiserum inhibited neutrophil infiltration into ulcer tissue and accelerated ulcer healing. Conclusion: Pentoxifylline accelerates healing of acetic acid induced gastric ulcer in rats. This effect may be due in part to reduction of neutrophil infiltration and inhibition of production of TNF-α by inflammatory cells. Early-phase inhibition of inflammatory response may accelerate ulcer healing.
Significant Increase in Prostaglandin E-Main Urinary Metabolite by Laxative Administration: Comparison with Ulcerative Colitis
Authors: Fujiwara Mutsunori , Okayasu Isao , Oritsu Masae , Komatsu Junko , Yoshitsugu Michiyasu , Katoh Yoshihisa , Bandoh Takafumi , Toyoshima Hiroshi , Kase Yoshio , Sugihara Kunio , Kanno Jun , Hayashi Yuzo
Published: April 2003

Objective: To assess the production of prostaglandin E2, an important chemical mediator in diarrhea induced by laxative administration, a prostaglandin E-main urinary metabolite (7α-hydroxy-5,11-diketotetranor-prosta-1,16-dioic acid, PGE-MUM) was measured in healthy volunteers and compared with the values of patients with ulcerative colitis. Methods: PGE-MUM was determined by a simplified immunoassay of bicyclic PGE-MUM and analyzed for the influence of laxative administration and active/remission phases of ulcerative colitis. Results: Administration of laxatives induced a significant increase in PGE-MUM in healthy volunteers. A significant elevation was also found in the active as compared with the remission phase of ulcerative colitis. The PGE-MUM levels were significantly correlated with our modified Talstad scores, clinical disease activity indices in ulcerative colitis. It was confirmed by time course studies of individual patients that changes in PGE-MUM correlated well with colitis activity. Conclusion: Laxative administration induces production of prostaglandin E2 as one of the chemical mediators, although its production grade is relatively low as compared with ulcerative colitis in the active phase.
Prospective Assessment of the Clinical Value of Anorectal Investigations
Authors: Vaizey Carolynne J. , Kamm Michael A.
Published: April 2003

Background/Aim: Anorectal physiological testing and imaging have become part of routine colorectal and gastro-enterological practice, but their clinical value is controversial. We prospectively evaluated the new diagnostic information, impact on management and prognostic information provided by anorectal testing. Methods: One hundred consecutive patients referred for testing were studied. The referring doctor’s diagnosis, reason for referral, planned management and expectation of the value of investigations were recorded. Incontinent patients underwent anorectal physiological testing and endo-anal ultrasound. Patients with constipation underwent anorectal physiological testing and a study of whole-gut transit time to distinguish between slow and normal transit. Constipated patients over age 45, or those younger patients who digitated to assist defaecation, also underwent evacuation proctography to identify large rectoceles. Results:  Fifty-one patients had faecal incontinence. Of 12 patients with suspected anterior external anal sphincter obstetric damage, all of whom were planned for surgical repair, 3 were unsuitable for repair, 3 had a normal sphincter, 2 had a weak but structurally intact sphincter, and 1 had internal anal sphincter damage only. Of 6 patients with failed anterior repair, 3 had a defect suitable for repeat repair, 2 had intact repairs and good function, and 1 had extensive damage requiring reconstructive surgery. The tests also influenced management for incontinent patients after haemorrhoidectomy surgery (n = 5), after fistula surgery (n = 5), with congenital abnormalities (n = 3), after cerebrovascular accident (n = 1) and those with no presumptive diagnosis (n = 15). Of the 20 patients referred with constipation, demonstration of a recto-anal reflex in 1 patient with a megarectum excluded the need for full-thickness biopsy. A further patient with altered electrosensation went on to have a neurological lesion defined. Definition of slow transit in some patients did not immediately affect management. New information or a change in management was provided in patients referred for pre-operative assessment (n = 13). Information was gained in only 1 of 7 patients with solitary rectal ulcer and in none of the 8 patients with anal pain. Conclusion: Anorectal assessment provides important diagnostic and prognostic information and directly alters management in patients with benign anorectal disorders.
Uncommon Metastasis of a Glioblastoma Multiforme in Liver and Spleen
Authors: Widjaja Adji , Mix Heiko , Gölkel Carsten , Flemming Peer , Egensperger Rupert , Holstein Andreas , Rademaker Jürgen , Becker Hartmut , Hundt Mathias , Wagner Siegfried , Manns Michael P.
Published: April 2003

A case of a glioblastoma multiforme is presented. Craniotomy was performed with total resection of the right temporal tumor. Postoperatively, the patient received adjuvant radiotherapy, but 6 months after therapy he developed severe nausea and weight loss. Recurrence of an intracranial tumor in the right temporal region with nodules in the liver and spleen were detected by CT scan. Fine-needle biopsies of the liver confirmed the diagnosis of a glioblastoma metastasis with characteristic immunohistochemical staining for glial fibrillary acidic protein. This rare case of an intracerebral glioblastoma metastasizing to liver and spleen was managed by systemic chemotherapy.
Starvation, Leptin and Epithelial Cell Proliferation in the Gastrointestinal Tract of the Mouse
Authors: Chaudhary M. , Mandir N. , FitzGerald A.J. , Howard J.K. , Lord G.M. , Ghatei M.A. , Bloom S.R. , Goodlad R.A.
Published: April 2003

Background/Aims: Leptin, the ob/ob gene product, is a recently discovered peptide hormone, secreted by adipocytes, which can act as a satiety factor to regulate food intake. Its levels thus will be related to the presence of food in the lumen of the gut, and food intake is one of the most potent stimuli for intestinal epithelial cell proliferation. Leptin has a variety of other actions and the aim of this study was to see if one of these was to stimulate mucosal growth. Methods: Three groups of mice were fed ad libitum, starved for 48 h or starved for 48 h and given twice-daily intraperitoneal injections of recombinant leptin (1 μg/g). Results: Starvation led to a 20% decrease in body weight and a similar decrease in the weights of the intestines. Starvation also markedly inhibited intestinal epithelial cell proliferation. Leptin had little effect on the small intestine and did not stimulate proliferation. However, in the hind gut it was associated with small but significant decreases in caecal weight, distal colon mitotic counts (p = 0.036) and in colonic crypt area (approximately 20%, p < 0.001). Conclusion: Leptin did not stimulate intestinal cell proliferation, however it did have a paradoxical inhibitory action on the caecum and colon.
Dose-Related Stimulatory Effect of Clarithromycin on Interdigestive Gastroduodenal Motility
Authors: Bortolotti M. , Annese V. , Mari C. , Lopilato C. , Porrazzo G. , Miglioli M.
Published: April 2003

Background/Aims: The effect on interdigestive gastroduodenal motility of different doses of clarithromycin, an antibiotic commonly used for Helicobacter pylori eradication, has been investigated. Methods: Gastroduodenal motility was recorded by means of a low-compliance manometric system in 15 healthy subjects. Thirty minutes after the first phase III of the migrating motor complex, clarithromycin (CLA) was infused intravenously at a dose of 100 mg in 5, 250 mg in 5 and 400 mg in 5 subjects, randomly and in a double-blind manner, continuing the recording for at least 1 h. A further study was carried out on 10 subjects, 5 of whom received 50 mg CLA and 5 normal saline with the same modalities. Results: After 100 mg CLA a premature gastroduodenal phase III ensued in all cases, which showed a duration, propagation velocity and wave frequency not significantly different from the spontaneous one and was followed by a clear phase I. A premature gastroduodenal phase-III-like activity occurred in 3 cases of 250 mg CLA and 2 cases after 400 mg CLA, followed by a very short or absent phase I and characterized by a long duration of the antral phase III, while in the remaining cases a long-lasting sequence of about 1/min of antral waves propagated to the duodenum appeared, sometimes preceded by an antral phase-III-like activity not propagated to the duodenum. After 50 mg CLA a premature phase III appeared in 2 cases, while a not premature phase III appeared in 2 cases after saline. Conclusion: CLA shows a dose-related stimulatory effect on interdigestive gastroduodenal motility varying from the initiation of a typical phase III to a prolonged sequence of gastroduodenal coordinated waves. These motor effects of CLA suggest potential therapeutic applications.
Severity of HCV-Induced Liver Damage Alters Glucose Homeostasis in Noncirrhotic Patients with Chronic HCV Infection
Authors: Konrad T. , Zeuzem S. , Toffolo G. , Vicini P. , Teuber G. , Briem D. , Lormann J. , Lenz T. , Herrmann G. , Berger A. , Cobelli C. , Usadel K.-H.
Published: April 2003

Background/Aims: To investigate the link between hepatitis C infection and glucose intolerance, we measured insulin sensitivity, glucose effectiveness and β-cell secretion in noncirrhotic HCV-infected patients with normal glucose tolerance according to WHO criteria as assessed by oral glucose tolerance tests. Methods: Glucose, insulin and C-peptide data from frequently sampled intravenous glucose tolerance tests were analyzed using the minimal modeling technique for glucose and C-peptide to determine insulin sensitivity, glucose effectiveness, first and second phase insulin secretion in noncirrhotic HCV-infected patients (n = 10) and in healthy control subjects (n = 10). Histological activity index (HAI) as well as the extent of fibrosis were evaluated by scoring liver biopsies. Results: Insulin sensitivity (2.72 ± 1.63 vs. 6.84 ± 1.20 10–4 min–1 per µU/ml, p < 0.01) and glucose effectiveness (2.29 ± 0.45 vs. 2.89 ± 0.39 10–2 min–1, p < 0.05) ere significantly lower in patients with HCV-induced liver disease. Insulin sensitivity was negatively related to serum alanine aminotransferase (r = –0.47, p < 0.05) and aspartate aminotransferase concentrations (r = –0.65, p < 0.05). Multiple linear regression analysis revealed a strong relation of insulin sensitivity with fibrosis score and HAI (r = –0.82, p < 0.02 for both). Second phase insulin secretion was significantly enhanced in HCV-infected patients (14.30 ± 2.04 vs. 8.29 ± 1.65 min–1, p < 0.05). Conclusions: HCV-infected patients with normal glucose tolerance are insulin and glucose resistant. The impairment of glucose tolerance appears to be closely related with the severity of HCV-induced liver damage.
Effect of Modified Sham Feeding and Insulin-Induced Hypoglycemia on Function of the Proximal Stomach
Authors: Mearadji B. , Straathof J.W.A. , Naaykens C. , Frölich M. , Lamers C.B.H.W. , Masclee A.A.M.
Published: April 2003

Background/Aim: Animal experiments have shown that vagal cholinergic stimulation causes an increase in proximal gastric tone, but little is known about the effect of vagal stimulation on proximal gastric motor function in humans. Vagal cholinergic stimulation can be elicited by modified sham feeding (MSF) or by insulin-induced hypoglycemia. The aim of our study was to investigate the effect of MSF and insulin-induced hypoglycemia on the motor and sensory function of the proximal stomach in humans. Methods: Eight healthy volunteers participated in random order in three experiments: (A) control experiment, (B) MSF and (C) intravenous insulin injection. Intragastric volume was recorded with a barostat set at a constant preselected pressure level (MDP + 2 mm Hg). Pancreatic polypeptide (PP) secretion was measured as an indicator of cholinergic tone. Results: PP secretion increased significantly after both MSF (p < 0.05) and insulin administration (p < 0.01). No changes in intragastric volume were seen after MSF, while intragastric volume increased significantly in response to insulin-induced hypoglycemia when compared to control (290 ± 43 vs. 148 ± 24 ml; p < 0.01). No differences in perception scores were seen between the three experiments. Conclusions: Vagal cholinergic stimulation by MSF has no effect on the motor function of the proximal stomach, while insulin-induced hypoglycemia causes a relaxation of the proximal stomach.
Retrospective Case Series Analysis of Patients with Inflammatory Bowel Disease on Azathioprine
Authors: Khan Zubair H. , Mayberry John F. , Spiers Nicky , Wicks Anthony C.
Published: April 2003

Objectives: The aim of this study was to look at our practice of using azathioprine and to compare our results with those in published trials both from the point of view of response and also the side-effect profile. Design: A retrospective case series analysis was done on patients with inflammatory bowel disease (IBD) who were on azathioprine at Leicester General Hospital. Methods: 111 patients (47 males, 64 females, mean age 35.3 years) were included from gastroenterology outpatients records between November 1997 and August 1998. Clinical and demographic details were collected. Response in Crohn’s disease was determined using the Harvey-Bradshaw index. In case of ulcerative colitis the following parameters were used: stool frequency; rectal bleeding, weight gain, and general well-being. Logistic regression was performed to look at the influence of age, sex and diagnosis in relation to the response/relapse rate. Results: The average duration of treatment with azathioprine was 28.6 months. The starting dose of 1.53 mg/kg was similar to the maintenance dose (1.51 mg/kg). 58 patients had Crohn’s disease and 53 patients were diagnosed with ulcerative colitis. 85 patients were steroid-dependent, 9 steroid-resistant, and 17 patients were started on azathioprine on the basis of extensive disease either seen at the time of endoscopy or radiologically. Improvement in clinical features at 3, 6 and 12 months was 69.5, 77 and 84.1%, respectively. 74% patients showed an improvement in relapse rates during the first year on azathioprine compared to 1 year prior to treatment. 68% patients who had shown improvement at 1 year were no longer taking steroids (p = 0.002). Logistic regression did not show any statistically significant influence of age, sex or diagnosis on response. 4.5% patients had leukopenia requiring dose reductions. Severe leukopenia (leukocyte count <2.5 × 109/l) occurred in 3.6% patients. Conclusions: Response rates in our IBD patients on azathioprine are comparable with those of the published data despite using a relatively smaller dose.