bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Different Octreotide Dosages on Splanchnic Hemodynamics and Glucagon in Healthy Volunteers
Authors: Schiedermaier P. , Brensing K.A. , Göke B. , Schätzle T. , Sauerbruch T.
Published: April 2003

Aims: This study evaluated the dependence of portal and mesenteric blood flow and plasma glucagon levels on octreotide dosage and its mode of application. Methods: Two groups of 10 individuals each received octreotide either subcutaneously (placebo, 100 and 200 µg) or intravenously (100-µg bolus i.v., 25 and 100 µg/h) in a double-blind, random order. Using Doppler ultrasound, we examined portal and mesenteric blood flow and measured plasma glucagon levels at regular intervals within a 4-hour period under fasting conditions. Results: Contrary to placebo, octreotide caused a decrease in portal blood flow (PVF) and in superior mesenteric artery blood flow (SMAF) together with an increase in the mesenteric pulsatility index (PI). The same total dose of 100 µg octreotide caused a similar PVF response, averaged over 4 h, given either subcutaneously (–28.0 ± 4.8%), intravenously (–29.4 ± 4.3%) or as a continuous infusion (–29.3 ± 4.6%). As concerns intravenous infusions, 100 µg/h was more effective than 25 µg/h (–37.8 ± 6.2 vs. –29.3 ± 4.6%). The PVF reduction remained constant during intravenous infusion, whereas glucagon levels decreased progressively over the entire observation time. Conclusions: The decrease in PVF is dependent on the octreotide dose. However, this is not constantly paralleled by a decrease in plasma glucagon concentration.
Study of a Primary Gastrinoma in the Common Hepatic Duct – A Case Report
Authors: Martignoni M.E. , Friess H. , Lübke D. , Uhl W. , Maurer Ch. , Müller M. , Richard H.-P. , Reubi J.-C. , Büchler M.W.
Published: April 2003

Primary endocrine neoplasms of the biliary tract are exceedingly rare. We report on a 60-year-old man with diarrhea, vomiting and gastroesophageal reflux disease, with a primary gastrinoma of the common hepatic duct. The tumor was positive for a variety of immunohistochemical markers. Postoperatively the patient’s symptoms disappeared and in the follow-up the patient was symptom free. To our knowledge, this is the first case in the literature of a primary gastrinoma in the common hepatic duct. The fact that the common hepatic duct is not located within the gastrinoma triangle made the diagnosis difficult and the distinct localization made the surgical treatment demanding.
Evidence for Decreased Salivary Function in Patients with Reflux Esophagitis
Authors: Kao C.H. , Ho Y.J. , ChangLai S.P. , Liao K.K.
Published: April 2003

It has been speculated that impaired salivary flow contributes to abnormal acid clearance of the esophagus in gastroesophageal reflux and results in reflux esophagitis (RE). To test this hypothesis, salivary functions were measured by quantitative salivary scintigraphies in patients with RE and in age- and sex-matched controls for comparison. Nineteen patients with RE and 36 healthy volunteers were enrolled in the study. After an intravenous injection of 5 mCi Tc-99m pertechnetate, sequential images of 1 min/frame were acquired for 30 min. The 1- and 15-min uptake ratios (UR) of the tracer in the four major salivary glands over the backgrounds were calculated. Saliva excretion was stimulated by 1 tablet of 200 mg ascorbic acid given orally 15 min after injection of the tracer, then the maximal excretion ratios (ER) of the four major salivary glands were calculated for the sialagogue stimulation. RE patients had lower values of 1st and 15th min UR and maximal ER than controls in the 4 major salivary glands. Poor salivary functions which represented a decrease in both UR and ER for patients with RE have been confirmed by quantitative salivary scintigraphy in this study.
Anti-Anisakis Antibodies in the Clinical Course of Crohn’s Disease
Authors: Guillén-Bueno Raquel , Gutiérrez-Ramos Rosario , Perteguer-Prieto Maria Jesús , Olveira-Martin Antonio , Fernandez-Blanco Ignacio , Pozuelo-García Alfonso , del Hoyo Carmen Cuéllar
Published: April 2003

Background: Human anisakidosis is a parasitic disease whose intestinal form shares several characterictics with Crohn’s disease (CD), like the ileocolonic location predominantly and the presence of granuloma. Methods: 73 CD patients diagnosed according to Lennard-Jones’ criteria were studied. The disease activity was measured by means of Harvey-Bradshaw Index. Different clinical variables were analyzed. Antigenic extract of Anisakis simplex larvae extracted from blue whiting was prepared. Determination of IgG, IgM, IgA and total specific immunoglobulin against A. simplex were carried out in sera by enzyme-linked immunosorbent assay. Immunorecognition patterns of these sera were realized by immunoblotting analysis. Results were compared with prevalence of antibodies anti-Anisakis in 251 healthy controls. Results: 29% of CD patients showed detectable specific total Ig (G+M+A) against A. simplex (95% CI, 19–41). For IgG, IgM and IgA the percentages were 44, 18 and 53% (95% CI, 32–56, 10–26, and 41–65) respectively. In positive specific total Ig cases CD was localized mainly in ileum. In IgG-, IgM- and IgA-positive cases the location was predominantly ileocolonic. CD activity index was higher for groups with positive IgA (2.86 vs. 5.55; p < 0.05). Conclusion: Patients with CD have high prevalence of specific immunoglobulin against A. simplex. Specific IgA are associated to higher activity index of CD.
Validation of the Spanish Version of the Inflammatory Bowel Disease Questionnaire on Ulcerative Colitis and Crohn’s Disease
Authors: López-Vivancos Josefa , Casellas Francesc , Badia Xavier , Vilaseca Jaime , Malagelada Juan-Ramon
Published: April 2003

The objective of this study is to validate the Spanish translation of the Inflammatory Bowel Disease Questionnaire (SIBDQ) on ulcerative colitis and Crohn’s disease by assessing its convergence validity, discriminatory power, reliability and sensitivity to change. For that purpose, 211 patients with inflammatory bowel disease (116 with ulcerative colitis and 95 with Crohn’s disease) completed the SIBDQ, the Psychological General Well-Being Index and the EuroQol. SIBDQ was repeated in those patients who remained in stable remission and in those with changes in clinical activity. Clinical activity was assessed by the Rachmilewitz and Harvey-Bradshaw indices. Correlations among scores of SIBDQ, EuroQol, Psychological General Well-Being Index and clinical indices of activity were all positive and comparable for both diseases (r = –0.50 to r = –0.70, p < 0.01). Analysis of variance showed that SIBDQ discriminates between different clinical degrees of activity. Cronbach’s α was 0.96 in ulcerative colitis and Crohn’s disease. SIBDQ was also highly reliable when it was repeated in clinically stable patients with ulcerative colitis (intraclass correlation coefficient = 0.82) and Crohn’s disease (intraclass correlation coefficient = 0.86). SIBDQ was sensitive to clinical changes in ulcerative colitis and in Crohn’s disease, whether patients entered remission (effect size –1.88 and –1.81, respectively) or relapsed (effect size 1.70 and 8.04, respectively). In conclusion, the Spanish version of the IBDQ has proven to be a valid, reliable and sensitive instrument to detect clinical changes in patients with ulcerative colitis and Crohn’s disease.
Resolution of Gastritis Induced by Helicobacter pylori 4–5 Weeks after Successful Eradication of Infection Using a Triple Therapy Regimen of Pantoprazole, Amoxycillin and Clarithromycin for One Week
Authors: Abdul Aal G.M. , Dajani A.I. , Nounou M. , Awad S. , Abdul Rasheed Z. , Gautam S. , Ukabam S. , Nayal S.
Published: April 2003

This open-label study was designed to determine the extent of histological resolution of gastritis induced by Helicobacter pylori infection 4–5 weeks after successful eradication of the infection. Eradication was achieved using a triple therapy regimen consisting of a twice daily dose of pantoprazole 40 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg taken for 1 week only. No other medications were given thereafter. Four biopsies were processed for histological examination of each patient, two from the antral and two from the corporeal mucosa, first at the start of the study and then again 4 weeks after cessation of the medication trial. Scoring for H. pylori colonization and the severity of gastritis was determined for each patient according to the Sydney system. 53 of 57 patients in this study had their H. pylori infection successfully eradicated by the regimen mentioned and could be histologically evaluated. According to the severity of gastritis in the antral mucosa, patients were studied in 3 groups: mild, moderate and severe gastritis. 17 of 19 cases with mild gastritis showed complete resolution of the inflammation, with residual inflammatory changes persisting in 2 cases only. 22 of the 26 cases with moderate gastritis showed almost complete recovery except for minor residual inflammatory changes as judged by irregularity of intracytoplasmic mucine storage. Persistent residual inflammatory changes in the lamina propria were detected in 4 cases. Of the 8 cases with severe gastritis 5 showed subsidence of the inflammatory changes, but the mucosa in these cases revealed some scarring, distortion of the glandular epithelium and atrophy. In 3 cases residual inflammation persisted. Conclusion: One-week therapy with a twice daily dose of pantoprazole 40 mg, clarithromycin 500 mg and amoxicillin 1,000 mg, used to eradicate H. pylori causing active inflammation of the gastric mucosa, has led to subsidence of the acute inflammatory changes in all the cases with residual inflammation persisting in 17%. Severe gastritis may cause irreparable damage to the gastric mucosa. The density of H. pylori colonization does not appear to be related to the severity of gastritis, nor to the successful eradication achieved.
Does Cimetidine Improve Prospects for Cancer Patients?
Authors: Siegers C.-P. , Andresen S. , Keogh J.P.
Published: April 2003

Background: Evidence first appeared in 1988 that cimetidine as an adjuvant may improve the survival of severely ill gastro-intestinal cancer patients when given peri- or postoperatively. Since then, several studies have appeared which suggest an anticancer activity for cimetidine, although few attempts have been made to corroborate their findings in large, placebo-controlled, double-blind studies. Method: We reviewed the literature concerning cimetidine’s potential anticancer activity, particularly with regard to gastro-intestinal cancers. Results: Most studies suggest that cimetidine may improve the outcome in cancer patients by a three-pronged mechanism involving (1) inhibition of cancer cell proliferation; (2) stimulation of the lymphocyte activity by inhibition of T cell suppressor function, and (3) inhibition of histamine’s activity as a growth factor in tumours. Conclusion: Bearing in mind the experimental evidence, as well as the potential and excellent safety profile of cimetidine, more studies are required and justified to clarify cimetidine’s protherapeutic activity.
Expression of Vesicular Monoamine Transporters in Endocrine Hyperplasia and Endocrine Tumors of the Oxyntic Stomach
Authors: Eissele Rolf , Anlauf Martin , Schäfer Martin K.-H. , Eiden Lee E. , Arnold Rudolf , Weihe Eberhard
Published: April 2003

Background: Gastric enterochromaffin-like (ECL) cells selectively express the vesicular monoamine transporter (VMAT) VMAT2, and enterochromaffin (EC) cells the VMAT1 isoform. Aims: We investigated whether VMAT isoform selection indicates the origin of endocrine hyperplasia and neoplasia from oxyntic ECL or EC cells and may be of prognostic significance in different types of gastric carcinoids. Methods: Tissue from patients with chronic atrophic gastritis (CAG), Zollinger-Ellison-syndrome (ZES), gastric carcinoids and neuroendocrine carcinoma (NEC) was investigated by immunohistology and in situ hybridization. Results: Endocrine cells forming diffuse, linear, and micronodular hyperplasia in CAG and ZES, as well as oxyntic microcarcinoids expressed both VMAT2 and chromogranin A (CgA) but neither VMAT1 nor serotonin. In five of six sporadic carcinoids VMAT2 and CgA but not VMAT1 were detected. One carcinoid was copositive for VMAT1 and serotonin but negative for VMAT2. Electron microscopy confirmed the VMAT2-positive tumors as ECLoma and the VMAT1-immunoreactive carcinoid as EComa. Conclusions: VMAT2 and VMAT1 are reliable markers for differentiation of gastric endocrine hyperplasia and neoplasia from ECL and EC cells, respectively. The significance of VMAT2 and VMAT1 as prognostic markers lies in the relatively poor prognosis for EComa compared to ECLoma, characterized by VMAT2 positivity. The absence of both VMAT2 and VMAT1 in NEC may indicate poor prognosis.
A New Simple Immunoassay for Detecting Helicobacter pylori Infection: Antigen in Stool Specimens
Authors: Fanti Lorella , Mezzi Gianni , Cavallero Annalisa , Gesu Giampietro , Bonato Claudio , Masci Enzo
Published: April 2003

Background/Aim: Several diagnostic tests are available for evaluating Helicobacter pylori (Hp) infection: histological examination, culture of gastric biopsy specimens, rapid urease test, urea breath test and serology. A recently marketed direct enzyme immunoassay (HpSA) detects Hp antigen in stool samples. The aim of our study was to evaluate overall diagnostic sensitivity, specificity and positive and negative predictive values of this new diagnostic test. Methods: We included in the study 84 patients (39 males and 45 females; mean age 49.57 years) with dyspeptic symptoms who were examined by upper gastrointestinal endoscopy. Exclusion criteria were previous treatment with proton pump inhibitors, bismuth compounds or antibiotics. During the endoscopic examination biopsies were taken from antrum and corpus for Hp culture and histological examination, and stool specimens were submitted to the laboratory to be stored until the HpSA test. Hp was judged to be present when culture or histology and culture were positive. The 13C-urea breath test was done only in culture-negative patients in whom either histology or immunoassay or both were positive. Results: Hp was found in 55 patients by both culture and histology. Stool antigen has been detected in 54 of the 55 Hp-positive patients, giving a sensitivity of 98.2% and a negative predictive value of 96.4%. In 2 out of 29 patients HpSA gave a positive result, but the biopsy-based methods were negative, resulting in a low rate of false-positives, with 93.1% specificity and 96.4% positive predictive value; the 13C-urea breath test confirmed these results as negative. Conclusion: Our results show that this new test is highly sensitive and specific for the detection of Hp infection, and it is satisfactorily reproducible.
Ethanol-Related Gastric Mucosal Damage: Evidence of a Free Radical-Mediated Mechanism and Beneficial Effect of Oral Supplementation with Bionormalizer, a Novel Natural Antioxidant
Authors: Marotta F. , Tajiri H. , Safran P. , Fesce E. , Ideo G.
Published: April 2003

Twenty-two healthy teetotal volunteers underwent gastroscopy during which biopsy samples from the antrum and body were taken for chemiluminescence assay, routine histology, and for malonyldialdehyde, xanthine oxidase and glutathione determination. Subjects were divided into 2 groups which, in a double-blind fashion, were randomly and orally given either (a) Bionormalizer 9 g at bedtime and 3 h prior examination, or (b) flavored sugar 9 g as placebo. During the second gastroscopy 40 ml of 80% ethanol were sprayed perendoscopically. Gastroscopy with biopsy was repeated 60 min later. As compared to the placebo group, subjects given Bionormalizer showed significantly reduced gastric mucosal damage at endoscopy and the histological level. When considering the placebo group, ethanol administration brought about a significant increase in the luminol-amplified chemiluminescence response in gastric mucosa as compared to the baseline value which was correlated with the histological score. The mean chemiluminescence value in the Bionormalizer group was significantly lower than in the placebo group. Ethanol ingestion brought about a significant increase in xanthine oxidase and malonyldialdehyde together with a decreased glutathione concentration. Bionormalizer significantly prevented such changes. The present data suggest that the natural antioxidant Bionormalizer when given orally promotes an effective protection against ethanol-induced gastric mucosal damage.
Barrett’s Esophagus: Disregulation of Cell Cycling and Intercellular Adhesion in the Metaplasia-Dysplasia-Carcinoma Sequence
Authors: Tselepis C. , Perry I. , Jankowski J.
Published: April 2003

The incidence of both esophageal adenocarcinoma and Barrett’s esophagus, a premalignant condition predisposing to this cancer, is rising rapidly. There is growing evidence that both of these conditions are related to the reflux of acid and bile into the esophagus. This results in inflammation and cell damage which initiates a sequence of events termed the metaplasia-dysplasia-carcinoma sequence in which the squamous epithelium is replaced by columnar epithelium exhibiting increasing degrees of dysplasia and overt malignancy. This sequence of events is underpinned by changes in cell cycling, such as accumulation of p16 and p53 mutations and increased cyclin D1 activity. Progression along this pathway is characterized by changes in intercellular adhesion, in particular, loss of adenomatous polyposis coli, reduced cadherin expression and increased catenin phosphorylation resulting in its nuclear translocation. Herein, we detail these molecular defects and propose how they may interrelate in an ordered progression in the development of esophageal adenocarcinoma.
Scientific Publications in Gastroenterology and Hepatology in Western Europe, USA and Japan in the Years 1992–1996: A Global Survey
Authors: Sorrentino D. , De Biase F. , Trevisi A. , Bartoli E.
Published: April 2003

Aim: To evaluate number and quality of publications in gastroenterology, hepatology and digestive endoscopy from Western Europe (Belgium, Denmark, France, Germany, Great Britain, Italy, the Netherlands, Spain, Sweden, Switzerland), Japan and USA over a recent 5-year period. Methods: We screened by computer for full liver/gastrointestinal-related articles and reviews the top 40% of journals (according to the annual rating of the SCI Journal Citation Reports; Institute for Scientific Information database) in most clinical and basic science disciplines in the years 1992–1996. To be credited with an article, a given country had to be the site of the first institution where the work was conducted. Papers were rated according to the impact factor of the Institute for Scientific Information and to the ratio impact factor/mean European impact factor. Data were also normalized for nondefense research and development expenditure. Results and Conclusions: As randomly tested, the computer search had an error of ± 5–10%. In Europe, Great Britain achieved the highest total impact factor and the highest number of papers. Most of the British impact factor came from publications in British journals. The total USA impact factor exceeded that of Europe by 20%. The average impact factor for a single paper was highest for the USA and, in Europe, for Germany. The temporal trend of total impact factor showed Spain improving by 9% per year, with Germany and Italy also displaying a substantial growth. Expressed per funds allocated in nondefense research and development, Great Britain and the USA had the highest cumulative impact factor.
Long-Term Use of Nonsteroidal Antiinflammatory Drugs and the Risk of Colorectal Adenomas
Authors: Breuer-Katschinski B. , Nemes K. , Rump B. , Leiendecker B. , Marr A. , Breuer N. , Goebell H.
Published: April 2003

Aims: Previous studies have suggested that the regular use of NSAIDs reduces the risk of colorectal adenomas. The aim of this study was to examine this association while taking possible confounding factors into account. Methods: The intake of drugs including NSAID intake during the last 20 years was assessed by means of a case-control study in 184 cases and matched hospital and community controls. Results: Overall, there were few individuals with a relevant drug intake for more than 5 years. NSAID intake for more than five years was associated with decreased risk in comparison with both control groups. The RR was 0.20 (0.04–1.04) compared with hospital and 0.21 (0.04–0.99) compared with population controls, the latter association being statistically significant. Subgroup analysis by type of drug revealed a significant protective effect only for long-term aspirin intake in relation to hospital controls, the RR being 0.09 (0.01–0.82). Conclusion: Our data support the hypothesis that there is a protective effect of NSAID intake of more than 5 years against the development of colorectal polyps.
Impact of Gastrin-Releasing Peptide on Intestinal Microcirculation after Ischemia-Reperfusion in Rats
Authors: Heuser Markus , Pfaar Oliver , Gralla Oliver , Gröne Herrmann Josef , Nustede Rainer , Post Stefan
Published: April 2003

We investigated the effect of gastrin-releasing peptide (GRP) and its antagonist RC-3095 on intestinal microcirculation after ischemia-reperfusion. Intestinal ischemia was induced in female Wistar rats by occlusion of the superior mesenteric artery for 40 min. Ten minutes prior to reperfusion, infusion of GRP or RC-3095 was started. A jejunal segment was exteriorized and the microhemodynamics of the mucosa and submucosa were examined by intravital microscopy and compared both with normal and ischemic controls (without application of the regulatory peptide). Ischemia-reperfusion significantly decreased functional capillary density from 891.2 ± 14.1 to 398.3 ± 11.4 cm–1. Capillary red blood cell velocity was reduced from 0.46 ± 0.01 to 0.37 ± 0.01 mm/s (p < 0.05). Furthermore, both sticking and rolling of leukocytes were enhanced. 3.4 ± 1.1% of the villi were not perfused at all. GRP infusion reversed the microcirculatory ischemia-reperfusion injury by increasing functional capillary density to 669.8 ± 8.3 cm–1 and red blood cell velocity to 0.62 ± 0.01 mm/s (p < 0.05). In addition, application of GRP resulted in a complete absence of stasis (0%) in the villi. Leukocyte-endothelium adherence remained unchanged when compared to the ischemic controls. In contrast, application of RC-3095 caused an aggravation of microcirculatory disturbances demonstrated by a markedly increased number of non-perfused villi (42.5 ± 4.2%; p < 0.05 vs. ischemic controls) and a significantly reduced functional capillary density (346.2 ± 8.4 cm–1, p < 0.05 vs. ischemic controls). In addition, RC-3095 led to an increased permanent leukocyte adherence in postcapillary venules whereas rolling was significantly reduced when compared to normal controls. We conclude that GRP in pharmacological doses has a protective effect on intestinal microcirculation during reperfusion. Furthermore, these data suggest that endogenous GRP may play a decisive role in the maintenance of microvascular integrity during reperfusion.
Analysis of Urgent Colonoscopy for Lower Gastrointestinal Tract Bleeding
Authors: Ohyama Takanori , Sakurai Yukihiro , Ito Masayoshi , Daito Kyoko , Sezai Shuuichi , Sato Yuzuru
Published: April 2003

Background: Three hundred and forty-five patients who underwent urgent colonoscopy for acute hematochezia during the past 20 years (from 1976 to 1995) were retrospectively analyzed. Methods: Urgent colonoscopy was defined as endoscopy performed within 24 h after a bleeding episode. Preparation was initially minimal with a water or glycerine enema. Recently, however, polyethylene glycol is used. Results: The overall diagnostic accuracy for bleeding site detection was 89.1% (307 cases). Successful insertion was made to the ileocecal region in 193 cases (55.9%). The disease most frequently discoverd by urgent colonoscopy was transient ischemic colitis (62 cases). Negative urgent colonoscopy specimens (18 cases) were later diagnosed by other methods as being small intestinal bleeding foci. In 10 cases, initial colonoscopy failed to detect the bleeding foci. Endoscopic hemostasis was performed in 48 cases. Permanent hemostasis succeeded in 32 cases (66.7%). Complications of urgent colonoscopy were fever after the examination (22 cases) and hypotension during endoscopy (7 cases). Conclusion: Urgent colonoscopy is considered to be a safe and useful examination for acute lower gastrointestinal bleeding and hemostasis.
Pneumatosis cystoides intestinalis: An Unexpected Finding in Intestinal Bleeding under Therapy with Phenprocoumon
Authors: Gabel Andreas , Müller Stefan , Häntzsche Katharina , Däuwel Nicole
Published: April 2003

Pneumatosis cystoides intestinalis is a rarely observed disorder on plain abdominal X-ray or colonoscopy examination. Although causing few complaints in adults, it can nevertheless lead to gastrointestinal bleeding. In the reported case, gastrointestinal bleeding was observed with coinciding pneumatosis and phenprocoumon therapy. After stopping anticoagulant therapy, pneumatosis vanished completely, thus suggesting that phenprocoumon is probably a further cause of the cystic disease. In the known list of drugs able to provoke pneumatosis, this case adds a new mechanism of affliction different to either immunosuppression or gas production.
EGF-Stimulated Polyamine Accumulation in the Colon Carcinoma Cell Line, Caco-2
Authors: Bauske Ruth , Milovic Vladan , Turchanowa Lyudmila , Stein Jürgen
Published: April 2003

Background: Polyamines (putrescine, spermidine and spermine) are ubiquitous molecules indispensable for cell proliferation. In the intestinal lumen they are present in high amounts. Polyamine accumulation in proliferating cells of the intestinal mucosa is high, and it occurs both by enhanced synthesis and by increased uptake from the lumen. Aims: To study mitogen-induced polyamine accumulation in the gut, we treated proliferating Caco-2 cells with epidermal growth factor (EGF) and measured the activity of ornithine decarboxylase (ODC) and putrescine uptake. Furthermore, we investigated whether EGF-induced changes in the apical membrane could be responsible for the effect of EGF on polyamine uptake in Caco-2 cells. Methods: Putrescine uptake, ODC activity and intracellular polyamine content were evaluated in the presence of 100 ng/ml EGF. To study the mechanisms of EGF-stimulated polyamine uptake, apical membrane vesicles were isolated, and putrescine uptake into the vesicles measured. Possible enrichment in brush border membrane cytoskeleton proteins (ezrin and villin) was assessed by Western blot. Results: Treatment with EGF induced an increase in ODC activity, which occurred within the first minutes of treatment and reached peak values after 3 h. In contrast, an increase in putrescine uptake was more sustained, with peak levels at 12 h. Both synthesis and uptake contributed to an over 60% increase in intracellular putrescine and spermidine after EGF treatment. There were no detectable changes in apical membrane cytoskeleton (as concluded by the absence of ezrin and villin enrichment in EGF-treated Caco-2 cells). However, in apical membrane vesicles isolated from EGF-pretreated cells, putrescine uptake was enhanced twofold. Conclusions: EGF stimulates both synthesis and uptake of polyamines in Caco-2 cells. Enhanced synthesis seems to ensure rapid supply with polyamines in the earliest stages of growth, while the uptake is responsible for the maintenance of high polyamine intracellular levels during late growth phases. EGF-stimulated polyamine uptake is apparently not a consequence of structural changes in the apical membrane, but is likely to occur by a distinct EGF-induced alteration of the polyamine transporter itself.
Substrate and Inhibitor Specificity of Butyrate Uptake in Apical Membrane Vesicles of the Rat Distal Colon
Authors: Schröder Oliver , Opritz Joanna , Stein Jürgen
Published: April 2003

Background/Aims: There is substantial evidence that transcellular flux of short-chain fatty acid (SCFA) absorption, at least in part, is mediated by an anion exchange process with bicarbonate. Methods: This anion exchange system was further characterized in apical membrane vesicles of the rat distal colon by studying substrate and inhibitor specificities of a variety of substituted monocarboxylic acids as well as of known inhibitors of the recently described monocarboxylate transporter MCT1 and MCT2. Results: SCFA transport was significantly reduced in the presence of branched and unbranched SCFAs and several bromo, chloro and mercapto analogues as well as nicotinic acid and L-lactate. In contrast, known inhibitors of monocarboxylate transporter proteins like stilbene derivatives, phloretin and 2-cyano-4-hydroxycinnamate did not inhibit bicarbonate-gradient stimulated butyrate transport. Kinetic analysis of increasing substrate concentrations of 3-mercaptopropionate, L-lactate and nicotinic acid showed saturation kinetics with apparent Ki of 6.1, 18.3 and 14.7 mmol/l, respectively. Conclusions: The data not only confirm earlier results that absorption of SCFAs in apical membranes of the rat distal colon is mediated by a relatively low affinity/high capacity SCFA–/HCO–3 exchange mechanism, but also indicate that although this anion transporter shares some functional similarities, is not identical with the recently cloned MCT isoforms.
[1-13C]Galactose Breath Test for Quantitative Measurement of Liver Function in a Short Period
Authors: Suzuki Shigeru , Ishii Yukimoto , Asai Satoshi , Kohno Tadashi , Mazaki Takerou , Takahashi Yasuo , Iwai Shigetomi , Ishikawa Koichi
Published: April 2003

Background: Using a rat model of hepatectomy, we investigated whether the severity of hepatopathy could be quantitatively measured from changes in expiratory 13CO2 levels after intravenous administration of [1-13C]galactose. Materials and Methods: Under nembutal anesthesia, 100 mg/kg [1-13C]galactose was administered to rats via the femoral vein, and expiratory 13CO2 levels were measured for 60 min. Then, 30, 70 or 90% hepatectomy was performed. In the control group, simple laparotomy was performed. Breath test was conducted 20 min after laparotomy. We examined the correlation of total 13CO2 output (S) or single point 13CO2 level (SP) every 5 min until 30 min, and at 45 and 60 min with liver weight/body weight (LW/BW) (%). Results: In the control group, the breath test graph reached a plateau level, but in all groups undergoing hepatectomy a plateau level was not reached during measurement. The correlation coefficient between S30 after [1-13C]galactose administration and LW/BW was 0.889 (p < 0.0001). The correlation coefficient between SP25 after [1-13C]galactose administration and LW/BW was highest, 0.923 (p < 0.0001). Conclusion: In the breath test with intravenously administered [1-13C]galactose, hepatopathy could be evaluated by measuring S30 and hepatopathy could be more accurately quantitatively evaluated by measuring SP25 over a short period.
Clastogenic Factors as Biomarkers of Oxidative Stress in Chronic Hepatitis C
Authors: Emerit Ingrid , Serejo Fatima , Filipe Paulo , Alaoui Youssefi Amina , Fernandes Afonso , Costa Adilia , Freitas Joao , Ramalho Fernando , Baptista Amelia , Carneiro de Moura Miguel
Published: April 2003

Background/Aims: Clastogenic factors (CFs) are composed of lipid peroxidation products, cytokines and other oxidants with chromosome-damaging properties. They are regularly observed after radiation exposure and in chronic inflammatory diseases, where they are supposed to be risk factors for carcinogenesis. It appeared of interest to investigate their presence in the plasma of patients with chronic hepatitis C. Methods: CFs are detected by chromosomal breakage studies. They were compared to malondialdehyde (MDA), total plasma thiols (t-SH), alanine aminotransferase (ALT), viral load and histological data. Results: CFs were increased in 19 of 20 patients, 16 had increased MDA levels and 15 had decreased t-SH levels. Mean values were significantly different from the 20 controls (p < 0.001). After the first 3 months of interferon treatment, all three markers showed significant improvement, but were not completely normalized. There was a positive correlation between CFs and necroinflammatory activity (p < 0.03), while MDA was correlated with fibrosis (p < 0.03). Viral load was correlated with necrosis and inflammation (p < 0.05). Conclusion: The presence of CFs in chronic hepatitis C confirms the occurrence of oxidative stress in this disease and could be useful in clinical trials for testing antioxidants. The CF test is a sensitive assay for the detection of oxidative stress and correlates with necroinflammatory activity.
Relationship between Ethanol-Induced Gastritis and Gastric Ulcer Formation in Rats
Authors: Liu Edgar S.L. , Cho Chi H.
Published: April 2003

Background/Aims: Patients with peptic ulcer diseases have a high prevalence of coexisting chronic gastritis. The mechanism of how gastritis leads to gastric ulcer formation is yet to be determined. The purpose of this study was to clarify the relationship between gastritis and gastric ulcer in rats. Methods: Ethanol (80% v/v, p.o.) was given repeatedly in rats to induce subchronic gastritis. Gastric ulcer was then induced by 60% acetic acid. Results: Findings showed that subchronic gastritis potentiated gastric ulcer formation. It also produced more apoptotic cells, together with an overexpression of tumor necrosis factor-α (TNFα) in the gastric mucosa. Inhibition of the production/release of TNFα by pentoxifylline prevented the increase in apoptosis and the enhancement of susceptibility to ulcerative damage by subchronic gastritis. However, such subchronic gastritis did not further affect the rate of ulcer healing in these animals. Conclusion: The induction of gastritis resulted in an activation of TNFα expression followed by apoptosis in the gastric mucosa. This could lead to an increase in the severity of ulcerative damage in the stomach.
Herpes simplex Virus Myelitis: Clinical Manifestations and Diagnosis by the Polymerase Chain Reaction Method
Authors: Nakajima Hideto , Furutama Daisuke , Kimura Fumiharu , Shinoda Keiichi , Ohsawa Nakaaki , Nakagawa Toshimasa , Shimizu Akira , Shoji Hiroshi
Published: April 2003

Herpes simplex virus (HSV) myelitis has previously been reported to be a form of acute ascending necrotizing myelitis caused by HSV type 2 (HSV-2). We studied neurological symptoms, clinical course, magnetic resonance imaging (MRI) findings, and diagnosis by polymerase chain reaction (PCR) methods in 9 patients with HSV myelitis. In 6 cases, disease onset was marked by sensorimotor disturbances of lower extremities and urinary disturbances, with the transverse myelopathy gradually ascending to the cervicothoracic spinal cord level. The other 3 cases showed transverse myelopathy without an ascending pattern. Six cases showed acute progression, while 3 cases showed a subacute course. There were 2 cases with recurrent episodes. Three patients recovered, however, in the remaining 6 patients severe sequelae such as paraplegia persisted despite antiviral therapy. MRI showed a hyperintense lesion on T2-weighted images. Gadolinium enhancement was observed in 2 cases, and 1 case showed a hyperintense lesion both on T1- and on T2-weighted images, suggesting hemorrhagic necrosis. HSV-2 was detected by PCR techniques in all 6 cases with an ascending pattern. HSV-1 DNA was detected in 2 and HSV-2 DNA in 1 of the 3 cases with a nonascending pattern. Our findings demonstrate diverse clinical manifestations of HSV myelitis.
Peripheral Facial Palsy: Etiology, Diagnosis and Treatment
Authors: Roob Gudrun , Fazekas Franz , Hartung Hans-Peter
Published: April 2003

Treatment options for peripheral facial palsy (PFP) are an often discussed problem in neurologic practice. Following a short description of the complex anatomy of the seventh cranial nerve we therefore review possible etiologies in the context of leading clinical signs, with idiopathic PFP or Bell’s palsy (BP) being most frequent. A rather typical clinical course of BP allows to focus differential diagnostic workup predominantly on the rapid identification of treatable infections such as with Herpes zoster or Borrelia burgdorferi. Neuroimaging studies are needed only in case of trauma, with slowly developing PFP or in the presence of associated signs and symptoms. As BP is characterized by an overall high rate of spontaneous recovery, major emphasis has to be put on avoiding complications by protecting the eye. Meta-analysis of four randomized controlled studies suggests a marginal benefit of steroids concerning eventual achievement of complete recovery. Beneficial effects of a combination of acyclovir and prednisone have also been claimed. While such therapies may be considered in patients with a presumptive bad prognosis, more general recommendations on medical treatment of BP will have to await further trials.
High-Dose Intravenous Immunoglobulin Treatment and Cerebral Vasospasm: A Possible Mechanism of Ischemic Encephalopathy?
Authors: Sztajzel R. , Le Floch-Rohr J. , Eggimann P.
Published: April 2003

A 46-year-old woman with a severe polyradiculoneuropathy treated with high-dose intravenous immunoglobulin (IVIg) presented an encephalopathy with increased blood flow velocities of the middle cerebral arteries (MCAs) detected by transcranial Doppler (TCD) studies. The similitude between this observation and another case recently reported of a patient suffering from Guillain-Barré syndrome (GBS) and cerebral blood flow abnormalities after IVIg treatment prompted us to investigate the responsibility of the IVIg therapy in the genesis of these blood flow alterations. We studied therefore by TCD 10 consecutive patients who underwent this treatment for different reasons. In 1 case we observed an asymptomatic, spontaneously reversible increase in the blood flow velocities of the MCAs consistent with a vasospasm and occurring 3–10 days after completion of the therapy. Stroke and ischemic encephalopathy have been reported as possible complications of IVIg treatment. In the case under discussion, clinical events appeared shortly after the administration of the IVIg therapy and responded favorably to a treatment with nimodipine. Other etiopathogenic mechanisms, in particular a CNS vasculopathic process related to the GBS itself, have to be considered as well. Further studies, with a larger number of patients, are therefore needed to evaluate the underlying mechanisms of blood flow abnormalities occurring sometimes in GBS patients after IVIg treatment.
A 52-Week Study of the Efficacy of Rivastigmine in Patients with Mild to Moderately Severe Alzheimer’s Disease
Authors: Farlow Martin , Anand Ravi , Messina Jr John , Hartman Richard , Veach Jeffrey
Published: April 2003

The efficacy of a centrally active cholinesterase inhibitor, rivastigmine tartrate (ENA 713; Exelon®), in patients with mild to moderately severe Alzheimer’s disease was evaluated in a 26-week open-label extension of a 26-week, double-blind, placebo-controlled study. By 52 weeks, patients originally treated with 6–12 mg/day rivastigmine had significantly better cognitive function than patients originally treated with placebo.
Effect of Fibrin Glue on Small and Large Bowel Anastomoses in the Rat
Authors: Shinohara K. , Kobayashi E. , Yoshida T. , Toyama N. , Kiyozaki H. , Fujimura A. , Miyata M.
Published: April 2003

Fibrin glue has been used as a hemostatic and adhesive agent for many years, but its efficacy in digestive surgery is still controversial. In this study, we evaluated the effect of fibrin glue on the healing of the small and large bowel anastomotic portions by measurement of the anastomotic bursting pressure. Further, the efficacy of fibrin glue in preventing intra-abdominal adhesion formation was assessed. Our results indicated that fibrin glue enhanced the resistance towards an elevation of intraluminal pressure in small bowel, but not in large bowel. Concomitantly, the glue did not significantly attenuate postoperative adhesion formation. A sealing action of fibrin glue might protect against bleeding and microleakage, resulting in beneficial effects on small bowel anastomosis.
Exogenous L-Arginine Protects Liver Microcirculation from Ischemia Reperfusion Injury
Authors: Uhlmann D. , Scommotau S. , Witzigmann H. , Spiegel H.-U.
Published: April 2003

Hepatic ischemia followed by reperfusion evokes an imbalance between the vasoregulatory compounds endothelin and nitric oxide (NO) followed by constriction of the vascular bed, leading to microcirculatory disturbances and reduced blood flow, thereby causing hypoxia and liver damage. The aim of this study was to protect the liver microcirculation by maintaining this delicate balance. Material and Methods: In an in vivo ischemia/reperfusion model with portal decompression by a splenocaval shunt, hepatic ischemia was induced for 30 min by Pringle’s maneuver. The effect of the NO donor L-arginine (400 mg/kg b.w. i.v.) was assessed by in vivo microscopy. Microhemodynamic studies, including the sinusoidal perfusion rate, diameters of hepatic sinusoids and postsinusoidal venules, leukocyte endothelium interactions and leukocyte velocity were performed. Microcirculatory data were compared with local tissue pO2 and serum transaminase levels. Results: After ischemia the diameters of sinusoids and postsinusoidal venules were significantly reduced to 76 ± 7 and 86 ± 10% respectively in the nontreatment group, but dilated to 102 ± 3 and 105 ± 7% in the group treated with L-arginine (p < 0.001). The percentage of permanently adherent leukocytes in sinusoids and venules was increased by ischemia, but L-arginine reversed this increase (p < 0.001). Perfusion rate was improved to 90 ± 2 compared with 83 ± 5% in the untreated group (p < 0.01). Systemic arterial blood pressure was not affected by administration of the NO donor. The postischemic increase in serum transaminase levels was diminished in the treatment group (ASAT: p < 0.05). Local postischemic hepatic tissue pO2 was significantly decreased to 45% of basal values after 30 min and to 55% after 60 min of reperfusion (p < 0.05). Administration of L-arginine results in a significant increase in local tissue pO2 to 86 and 106% of basal values respectively (p < 0.05). Conclusion: These data indicate that L-arginine improves hepatic microcirculation after warm ischemia by increasing sinusoidal perfusion rate and by diminishing leukocyte endothelium interactions. Maintained integrity of microcirculation is associated with sufficient oxygen supply and improved hepatocellular function.
Correlations among Expression of Intercellular Adhesion Molecule 1, Cellular Infiltration, and Coronary Arteriosclerosis during Chronic Rejection Using the Rat Heart Transplantation Model
Authors: Hamano K. , Ito H. , Shirasawa B. , Gohra H. , Katoh T. , Fujimura Y. , Esato K.
Published: April 2003

Immunologic mechanisms contribute to the development of coronary arteriosclerosis. In this study the rat heart transplantation model was used to investigate correlations among the expression of intercellular adhesion molecule 1, cellular infiltrate, and coronary arteriosclerosis during chronic rejection. Lewis rats served as heart donors and F-344 rats as recipients. Heart transplantations were performed heterotopically. The recipients were treated with ciclosporin A (5 mg/kg/day) by daily intramuscular injection for 30 days, beginning on the day of transplantation. Rejection grade and the intimal area were measured. The expression of intercellular adhesion molecule 1 and the numbers of infiltrating CD4- and CD8-positive cells and macrophages were examined immunohistochemically. The area of the intima was significantly increased in the allograft group after transplantation. In the allograft group, the level of expression of intercellular adhesion molecule 1 was considerably increased over the same time period. There was increased cellular infiltration in the 60-day group, and many expressed intercellular adhesion molecule 1. The expression of intercellular adhesion molecule 1 in vascular endothelium, infiltrating cells, and the sarcolemmal membrane of myocytes remained constant up to 120 days in the allograft group. In the allograft group, the number of infiltrating CD4- and CD8-positive cells and macrophages increased significantly between 30 and 60 days, and the infiltration of these cells remained constant. Continuous expression of intercellular adhesion molecule 1 induces the infiltration of T cells and macrophages, and the inflammation caused by such cells and their soluble products contributes to the arteriosclerotic process.
Surgical Stress Induces Decreased Expression of Signal-Transducing Zeta Molecules in T Cells
Authors: Ichihara F. , Kono K. , Sekikawa T. , Matsumoto Y.
Published: April 2003

Surgical stress is known to induce immunosuppression of T cell functions, but the mechanism behind this phenomenon is unclear. The purpose of this study was to determine whether surgical stress affects the expression of signal-transducing ζ molecules in peripheral T cells. In the present study, the expression of signal-transducing ζ molecules was studied by flow-cytometric analysis of permeabilized cells in peripheral blood mononuclear cells from 28 patients before and after surgery. The results demonstrate that T cell receptor (TCR) ζ levels in the peripheral T cells were lower on the 2nd or 3rd postoperative days (POD) compared to the preoperative period and recovered on the 7th POD in patients who received major surgery. Surface CD3 ε levels were also decreased after surgery but did not recover on the 7th POD. Culturing of T cells from the preoperative period with autologous monocytes from the 2nd POD induced a decreased expression of their TCR ζ. The reduction was prevented by the addition of catalase, a selective scavenger of hydrogen peroxide, indicating that this phenomenon was mediated by hydrogen peroxide. These results suggest that the decreased expression of TCR ζ molecules in peripheral T cells was induced by surgical stress, and was mediated by hydrogen peroxide derived from monocytes.
Effects of Hyperbaric Oxygen Treatment on Neutrophil Activation and Pulmonary Sequestration in Intestinal Ischemia- Reperfusion in Rats
Authors: Tjärnström J. , Wikström T. , Bagge U. , Risberg B. , Braide M.
Published: April 2003

Treatment with hyperbaric oxygen (HBO) has shown promising results in some models of ischemia, the major effect being a reduction in the local ischemic damage. The present study investigated the effects of HBO treatment on neutrophil activation and leukosequestration during reperfusion following intestinal ischemia in a rat model. The superior mesenteric artery was clamped for 2 h and subsequently reperfused for 90 min. One group of male Sprague-Dawley rats (n = 9) was given HBO and another group (n = 9) served as controls. Prior to ischemia, leukocytes and erythrocytes were separated, radiolabelled with 111ln and 51Cr, respectively, and reinfused. Leukocyte transit factor, the ratio between the mean passage time of leukocytes and erythrocytes was used to quantitate leukosequestration and the fraction of circulating, spontaneously nitroblue tetrazolium (NBT)-reducing neutrophils was used to measure the degree of neutrophil preactivation. HBO treatment reduced the level of leukocyte pooling significantly, especially in the lungs but also, to a minor degree, in the systemic vascular bed. The percentage of NBT-positive cells increased in all animals after reperfusion, but the increase was significantly reduced by HBO treatment. In conclusion, HBO treatment reduces leukosequestration and neutrophil preactivation following intestinal ischemia-reperfusion.