bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidermal Growth Factor Protects against Pancreatic Damage in Cerulein-Induced Pancreatitis
Authors: Warzecha Zygmunt , Dembinski Artur , Konturek Peter Ch. , Ceranowicz Piotr , Konturek Stanislaw J.
Published: April 2003

Epidermal growth factor (EGF) exhibits gastroprotective and ulcer-healing action. These observations prompted us to determine the influence of EGF on cerulein-induced pancreatitis (CIP) in the rat. Acute pancreatitis was induced by subcutaneous infusion of cerulein (10 μg/kg/h) for 5 h. Initially EGF was administrated twice at doses of 1, 5, 10 or 100 μg/kg s.c. (first injection 30 min prior to cerulein infusion, and the second injection 2.5 h after the start of cerulein infusion) and from this part of study 10 μg/kg was chosen for the next experiments. CIP led to a significant decrease in DNA synthesis and a reduction in pancreatic blood flow (PBF) by 42 and 30%, respectively, as well as a significant increase in pancreatic weight, plasma amylase concentration, plasma interleukin-1β (IL-1β) level and the development of the histological signs of pancreatic damage with marked edema, leukocyte infiltration and vacuolization of acinar cells. Treatment with EGF attenuated the pancreatic tissue damage in CIP as manifested by partial reversal of the drop in DNA synthesis and improvement of pancreatic histology. Moreover, EGF administration attenuated the fall in PBF and significantly reduced the cerulein-evoked increase in pancreatic weight. Also plasma amylase and IL-1β were decreased in rats treated with EGF. We conclude that: (1) EGF exerts a protective effect against CIP, and (2) the beneficial activity of EGF in CIP seems to depend on the increase in pancreatic cell proliferation, the reduction in cytokine generation and the attenuation of the fall in PBF.
Immunohistochemical Localization of Calcitonin Gene-Related Peptide in the Human Gastric Mucosa
Authors: Tani Norio , Miyazawa Masayuki , Miwa Takeshi , Shibata Masahiro , Yamaura Tetsuaki
Published: April 2003

Background/Aim: There have been only a few studies on the distribution of calcitonin gene-related peptide (CGRP) in the human stomach, in which it was stated that CGRP fibers are rare in that organ. The aim of the present study was to investigate the immunohistochemical localization of CGRP in the human gastric mucosa obtained by endoscopic biopsy from patients with gastric ulcers. Methods: Immunohistochemistry was carried out according to the indirect immunoperoxidase method using an anti-human CGRP antibody. Biopsies were taken from the ulcer margin in 18 patients (age 37–78, average 57.4 years) and from two endoscopically normal portions (antrum and body) in 7 other patients (age 36–65, average 51.0 years). One biopsy specimen was obtained from each portion. Results: Twelve of the eighteen biopsy specimens from the ulcer margin, 6 of the 7 biopsy specimens from normal portions of the antrum and 3 of the 7 biopsy specimens from normal portions of the body showed CGRP-immunoreactive staining. Intense staining was more marked in the specimens from the ulcer margin compared to those of the normal portions. Conclusions: CGRP immunoreactivity was observed in the human gastric mucosa in considerable abundance, and it is presumed that CGRP might participate in a restoration mechanism of the ulcer.
Prokinetics in Patients with Gastroparesis: A Systematic Analysis
Authors: Sturm Andreas , Holtmann Gerald , Goebell Harald , Gerken Guido
Published: April 2003

Background: The relative potency of prokinetics in patients with gastroparesis has not been systematically studied. This study, therefore, aimed to assess the available data and to compare the effects of different prokinetics on symptoms and gastric emptying rates in patients with gastroparesis. Methods: A systematic search of the literature was performed, covering the period 1980 to March 1998. All identified studies were reviewed and the following data elements assessed: characteristics of study populations; sample sizes; treatment regimes; drug doses; study design; main outcome variables, and the validity of measurements. Results: In 36 studies, 514 patients were treated with prokinetics p.o. Most studies had methodological limitations (i.e. nonvalidated measurement of symptoms or unblinded treatment). The mean improvement in gastric emptying and the reduction in the symptom score was higher in the open trial group than in patients treated double-blind. Overall, erythromycin seems to have had the strongest effect on gastric emptying as compared to domperidone, cisapride or metoclopramide. Concerning gastrointestinal symptoms, the symptom scores appeared to improve more during treatment with erythromycin than with domperidone, metoclopramide or cisapride. Conclusions: Most of the available trials have methodological limitations; this limits the conclusions. However, the data suggest that the motilin-agonist erythromycin is superior with regard to the acceleration of gastric emptying, while both erythromycin and domperidone appear to be the most effective with regard to improvements in the symptom score. Additionally, there is a lack of association between changes in gastric emptying times and improvements in symptoms.
β-Microseminoprotein in Gastric Carcinoids: A Marker of Tumour Progression
Authors: Weiber Håkan , Borch Kurt , Sundler Frank , Fernlund Per
Published: April 2003

Gastric carcinoid disease may have a highly varying clinical course depending on the malignancy of the tumour. Many biochemical markers, such as peptides and biogenic amines, have been found in carcinoid tumour tissue but none has been reported to be useful as a predictor of the degree of malignancy of the carcinoid. β-Microseminoprotein is a small disulphide-rich protein with unknown function present in the secretions on most mucosal surfaces in the body, including the stomach where it is also found in some endocrine cells. We have studied β-microseminoprotein by immunohistochemistry in the tumour tissue of 29 patients with gastric carcinoid disease. β-Microseminoprotein was present in the tumour tissue in 62% of the patients and its presence was correlated to tumour diameter and tissue invasion depth. The presence of β-microseminoprotein in tumour tissue was corroborated by in situ hybridisation. All 4 patients with the solitary sporadic type of tumour and all 6 patients with metastasis had positive immunostaining of the tumour tissue. The serum concentration of β-microseminoprotein, measured by radioimmunoassay, was increased in all but 2 of 13 patients with gastric carcinoid disease. To a large part the increase was due to the concomitant atrophic corpus gastritis. We conclude that β-microseminoprotein in tumour tissue is a marker of tumour progression and that measurement of β-microseminoprotein in serum is less informative than immunohistochemistry.
Ultra-High-Dose Lanreotide Treatment in Patients with Metastatic Neuroendocrine Gastroenteropancreatic Tumors
Authors: Faiss S. , Räth U. , Mansmann U. , Caird D. , Clemens N. , Riecken E.-O. , Wiedenmann B.
Published: April 2003

Background: Symptomatic control and occasionally even tumor regression of functional neuroendocrine tumors (NET) of the gastroenteropancreatic (GEP) system can be achieved by somatostatin analogues. Assuming a dose-dependent antiproliferative effect of somatostatin analogues, we performed a study with the somatostatin analogue lanreotide in ultra-high dosages in patients with progressive, metastatic GEP NET. Patients and Methods: 30 patients with metastatic GEP NET, progressive during treatment with somatostatin analogues (≤1.5 mg/day) and/or interferon-α, underwent ultra-high-dose lanreotide therapy (5 mg lanreotide s.c. three times a day). Tumor growth was evaluated every 3 months. Serum chromogranin A, serum serotonin as well as urinary 5-hydroxyindoleacetic acetic acid levels were also determined at 3-month intervals. In patients with functional tumors, tumor-related symptoms were documented. Results: After a 1-year treatment period with ultra-high-dose lanreotide, 1 complete and 1 partial remission were observed in patients with functional midgut NET. Eleven patients had stable disease and 11 patients showed continuing tumor growth after 3–12 months of treatment. Symptoms decreased significantly during therapy. Conclusions: Our data show that ultra-high-dose lanreotide treatment in patients with metastatic GEP NET can lead to control of both symptoms and proliferation in at least some patients refractory to conventional therapies.
Genomic Imprinting of IGF-II and H19 in Adult Human Pancreatic Tissues
Authors: Micha Anne E. , Hähnel S. , Friess Helmut , Büchler Markus W. , Adler Guido , Gress Thomas M.
Published: April 2003

Background/Aim: Genomic imprinting is a chromosomal modification causing differential expression of maternal and paternal alleles. Loss of imprinting (LOI) of IGF-II and H19 has been suggested to be an early oncogenic event in cancerogenesis. Aim of the present study was to describe the status of IGF-II and H19 imprinting in adult human pancreatic tissues. Methods: Allele-specific gene expression was studied using RNA and DNA from human pancreatic cancer, chronic pancreatitis, and normal pancreas tissues heterozygous for ApaI (IGF-II) or RsaI (H19) restriction fragment length polymorphism. Reverse-transcriptase polymerase chain reaction products were digested with either ApaI or RsaI and analyzed on agarose gels to study the status of allelic expression. The expression level of H19 and IGF-II was studied on Northern blots or by polymerase chain reaction. Results: H19 was imprinted in normal pancreas and in chronic pancreatitis. H19 LOI was observed in 1 of 4 informative cancer tissues and was not associated with increased H19 transcript levels. Biallelic expression of IGF-II was found in 6 of 10 informative cancer tissues and in 6 of 9 informative normal tissues. In chronic pancreatitis, the IGF-II gene was imprinted in all informative samples. IGF-II mRNA was not overexpressed in the tissues showing LOI. Conclusion: Low frequencies of H19 LOI and the lack of correlation between biallelic expression and overexpression observed for both H19 and IGF-II suggest that LOI of H19 and IGF-II is not a relevant oncogenic factor during human exocrine pancreatic cancerogenesis.
Chronic Ethanol Administration Induces Oxidative Alterations and Functional Impairment of Pancreatic Mitochondria in the Rat
Authors: Grattagliano Ignazio , Palmieri Vincenzo , Vendemiale Gianluigi , Portincasa Piero , Altomare Emanuele , Palasciano Giuseppe
Published: April 2003

Pancreas is known to be vulnerable to ethanol (ETOH) at high doses, but little is known about the effect of lower doses. Therefore, in this study, the levels of glutathione (GSH), sulfhydryl proteins (P-SH), carbonyl proteins, malondialdehyde (MDA), and adenosine triphosphate (ATP) production were determined in the pancreatic tissue and mitochondria of rats fed for 8 weeks with 3% ETOH. ETOH decreased the pancreatic pool of ATP, while GSH and P-SH also decreased in mitochondria. MDA concentrations increased both in the pancreas and mitochondria, while carbonyl proteins increased only in mitochondria. Pancreatic cells of ETOH-treated rats were frequently affected by cytoplasmic vacuolization and swelling; these alterations were often associated with ductular dilatation. In conclusion, ETOH produces oxidative and morphologic alterations in the pancreas of the rat, including impairment of mitochondria. These effects may represent basic mechanisms of ETOH-induced pancreatic injury.
Rapid and Reproducible Quantification of Hepatitis C Virus cDNA by Fluorescence Correlation Spectroscopy
Authors: Weiner Olaf H. , Alt Michael , Dürr Ralf , Noegel Angelika A. , Caselmann Wolfgang H.
Published: April 2003

Background/Aims: Standard methods for hepatitis C virus (HCV) RNA quantification are time-consuming and often hampered by low sensitivity. Therefore, we aimed to test whether fluorescence correlation spectroscopy (FCS) could be used to read out HCV polymerase chain reactions (PCR). Methods: A single-step reverse transcriptase (RT) PCR system was adjusted to the clinically relevant range of 1 × 103 to 5 × 106 HCV cDNA copies/ml serum. Unpurified amplification mixtures were analyzed by FCS and controlled by HPLC analysis. Results: The outcome of HCV RNA quantitation was nearly identical no matter whether FCS or HPLC techniques were used. FCS-generated standard curves displayed sufficient linearity to allow reproducible determinations. The intraserial variation of cDNA quantification after PCR amplification was ±3.2%, the interserial variation ±4.3%. Repeated quantifications of HCV genotype 1b RNA from the sera of 8 patients revealed titers from 1 × 104–5 × 106 genome equivalents/ml. The results correlated significantly (r = 0.755; p = 0.03) with a widely used commercially available assay. Conclusion: FCS may become a useful tool for rapid and reproducible HCV RNA quantification in the future.
Two-Month Glucocorticoid Treatment Increases Proliferation in the Stomach and Large Intestine of Rats
Authors: Gunin Andrei G. , Nikolaev Dmitrii V.
Published: April 2003

Background/Aims: It has been shown that acute or short-term treatments with glucocorticoids lead to a marked decrease in proliferation in the stomach and large intestine. The effects of more prolonged glucocorticoid treatment on cell renewal in these organs are not known. The present work was therefore undertaken to examine the proliferative activity in the stomach and colon during 2 months of glucocorticoid treatment in comparison with shorter treatments. Methods: Rats were treated with either the glucocorticoid triamcinolone acetonide or vehicle for 63, 33 or 3 days. Proliferation was assessed in the glandular epithelium of the fundal part of the stomach and in the epithelium of the colonic crypts using three criteria: the mitotic index; the bromodeoxyuridinelabelling index, and the proliferating cell nuclear antigen-labelling index (percentage of mitotic or labelled cells). Results: Treatment with glucocorticoid for 63 days resulted in a very significant increase in all proliferative parameters tested in the gastric mucosa and the colonic crypts. On the contrary, treatments with glucocorticoid for 3 or 33 days had a marked inhibitory influence on proliferation in these tissues. Conclusion: As opposed to treatments for 3 or 33 days, glucocorticoid treatment for 2 months leads to an increase in the number of cycling cells in the gastric and colonic mucosae.
Application of the Colon-Simulation Technique for Studying the Effects of Saccharomyces boulardii on Basic Parameters of Porcine Cecal Microbial Metabolism Disturbed by Clindamycin
Authors: Breves Gerhard , Faul Karin , Schröder Bernd , Holst Hasso , Caspary Wolfgang F. , Stein Jürgen
Published: April 2003

Aims: The present study analyzed the effects of Saccharomyces boulardii on the biochemical parameters of microbial hindgut metabolism disturbed by clindamycin. Methods: The experiments were carried out under in vitro conditions using the semicontinuous colon-simulation technique. This technique is standardized for quantitatively measuring parameters of microbial hindgut metabolism. The fluid and particle phase of pig hindgut contents were used for the in vitro incubations. The 5-day control period was followed by clindamycin exposure alone (312.5 mg/day for 5 days) or by a combined treatment of clindamycin and S. boulardii (400 mg/day for 5 days). Results: Clindamycin resulted in significant decreases in production rates of short-chain fatty acids (SCFAs) which were associated with substantial changes in molar SCFA proportions at the expense of butyrate. These effects could at least partly be compensated for by S. boulardii, in particular by enhancements of acetate and propionate fermentation to control levels. In contrast, butyrate fermentation could not be reconstituted. In a second experiment the potential use of S. boulardii as a substrate for hindgut microbial metabolism was studied by comparing living and autoclaved yeast. Propionate and butyrate fermentation rates were unaffected whereas acetate fermentation tended to be higher in the presence of living yeast. Conclusions: S. boulardii can be effective to compensate for changes in microbial fermentation in response to antibiotic treatment. Despite the lack of statistical significance it might be concluded that the increase in fermentation end products can only partly be explained by the utilization of the yeast as a substrate for microbial metabolism.
Functional Expression of HGF and Its Receptor in Human Colorectal Cancer
Authors: Otte Jan-Michel , Schmitz Frank , Kiehne Karlheinz , Stechele Hans U. , Banasiewicz Tomas , Krokowicz Piotr , Nakamura Toshikazu , Fölsch Ulrich R. , Herzig Karl-Heinz
Published: April 2003

Background: Hepatocyte growth factor (HGF) stimulates proliferation, migration and morphogenesis of epithelial cells by specific binding to its receptor c-met. Overexpression of HGF or c-met has been reported for human gastric or pancreatic cancer. In colorectal cancer overexpression of c-met but not HGF has been shown. However, elevated HGF serum levels have been detected in colorectal cancer patients. Therefore, the present study was performed to investigate expression patterns of both c-met and HGF in colorectal cancers and metastasis in comparison to normal mucosa. Furthermore, the mitogenic actions of HGF on colorectal cancer cells were studied in vitro. Methods: Expression of c-met and HGF were analyzed by RT-PCR and Western blotting and localized in the tissues utilizing immunohistochemistry. Mitogenic effects of HGF were determined in four human colon cancer cell lines by 3H-thymidine incorporation studies. Results: C-met and HGF mRNA were detectable in 60% of the normal specimen, but in the majority of cancer samples, and in just 33% of the liver metastasis. In cancer samples a coexpression of c-met and HGF was detected in 77% of the specimens. The extent of protein expression of receptor and ligand correlated with the mRNA expression. Moreover, c-met protein expression was increased 2- to 3-fold in colorectal cancers. C-met was detected in cells of epithelial origin, whereas HGF was expressed by mesenchymal cells. In vitro, HGF significantly stimulated cell growth in all four cell lines. Conclusion: Overexpression of c-met protein in colorectal cancers is combined with an expression of HGF in the majority of cases suggesting a paracrine manner of growth enhancement, while only a weak expression of c-met or HGF was detected in metastatic tissues.
Elevated Soluble Tumour Necrosis Factor Receptor Serum Concentrations and Short-Term Mortality in Liver Cirrhosis without Acute Infections
Authors: Reichel Christoph , Sudhop Thomas , Braun Barbara , Kreuzer Karl-Anton , Hahn Corinna , Look Markus P. , von Bergmann Klaus , Sauerbruch Tilman , Spengler Ulrich
Published: April 2003

Background: Serum concentrations of the soluble 75-kDa tumour necrosis factor receptor (sTNF-R 75) are elevated in patients with severe liver disease and may be linked to mortality as well as to prognostic markers related to clinical outcome and metabolic functions in patients with liver cirrhosis. Patients and Methods: We prospectively studied the relation of sTNF-R 75 to Child-Pugh score points and serum markers of bile acid (total serum bile acids and 7α-hydroxycholesterol), lignocaine (lignocaine metabolite (MEGX) liver function test results) and albumin metabolism (albumin and prealbumin) in 10 healthy individuals and 30 patients with cirrhosis, all free of acute infections. In patients with cirrhosis mortality was recorded for 15 months. Results: Soluble TNF-R 75 concentrations correlated with Child-Pugh score points (r = 0.440, p = 0.015), MEGX test results (rS = –0.604, p < 0.001) and prealbumin (rS = –0.527, p < 0.001) in cirrhosis. Nonsurviving patients had almost threefold higher median sTNF-R 75 concentrations (29 ng/ml) than survivors (11 ng/ml) (p = 0.003). Soluble TNF-R 75 serum concentrations with an optimal cut off > 14 ng/ml were significantly more accurate in predicting patient mortality than Child-Pugh score points in a receiver-operator characteristic curve analysis. Conclusion: Soluble TNF-R 75 serum concentrations appear to be a promising new risk factor for mortality in patients with cirrhosis without acute infections.
Refractory Sprue Syndrome with Clonal Intraepithelial Lymphocytes Evolving into Overt Enteropathy-Type Intestinal T-Cell Lymphoma
Authors: Daum Severin , Hummel Michael , Weiss Dajana , Peters Michael , Wiedenmann Bertram , Schäper Frank , Stein Harald , Riecken Ernst-Otto , Foss Hans-Dieter
Published: April 2003

Introduction: Recently, patients with refractory sprue have been shown to contain a clonal proliferation of phenotypically abnormal intraepithelial lymphocytes in their intestine. Whether this signifies early enteropathy-type intestinal T-cell lymphoma (EITCL) or a reactive condition is not clear. We report on a patient presenting with the findings of refractory sprue who subsequently developed overt EITCL. Material and Methods: Duodenal biopsies from 1997 (refractory sprue) and duodenal and jejunal biopsies from 1998 (intestinal T-cell lymphoma) were compared by immunohistochemistry and PCR for the detection of T-cell receptor (TCR)-γ gene rearrangements. Clonal PCR products were sequenced. Results: The duodenal biopsies from both 1997 and 1998 and the jejunal tumor biopsy showed villus atrophy and an increase of intraepithelial lymphocytes with an abnormal immunophenotype (CD3+, CD4–, CD8– and TCR-β–). In all duodenal specimens including the one from 1997, and the jenunal tumor biopsy, an identical clonal amplificate was detected by enzymatic amplification of the TCR-γ gene. Conclusion: These data suggest that refractory sprue containing a clonal proliferation of phenotypically abnormal intraepithelial lymphocytes may represent an early manifestation of EITCL. The detection of immunohistochemical negativity for several antigens normally found on intraepithelial lymphocytes such as CD8 or the TCR-β chain in combination with clonal T-cell populations by PCR may be helpful in identifying refractory sprue with a malignant transformation.
Potential Uses of Intravenous Proton Pump Inhibitors to Control Gastric Acid Secretion
Authors: Metz David C.
Published: April 2003

Proton pump inhibitors are the most effective agents for suppressing gastric acidity and are the preferred therapy for many acid-related conditions. While proton pump inhibitors have been accessible in intravenous formulations in several European countries, they have been available only as oral drugs in the United States. In the near future, the proton pump inhibitor pantoprazole is likely to become available in an intravenous formulation for American patients. Potential uses for intravenous proton pump inhibitors include treatment of Zollinger-Ellison syndrome and peptic ulcers complicated by bleeding or gastric outlet obstruction, as well as prevention of stress ulcers and acid-induced lung injury. These intravenous proton pump inhibitors are also likely to be beneficial to patients undergoing long-term maintenance with oral proton pump inhibitors who cannot take oral therapy for a period of time. Intravenous pantoprazole is especially distinguished in its lack of clinically relevant drug interactions, and it requires no dosage adjustment for patients with renal insufficiency or with mild to moderate hepatic dysfunction. Both omeprazole and pantoprazole are well tolerated in both oral and intravenous forms. Although further studies are needed to define their roles clearly, the availability of intravenous formulations of proton pump inhibitors will certainly assist with the treatment of gastric acid-related disorders.
Effect of Ecabet Disodium, a Novel Locally-Acting Antiulcer Drug, on Epithelial Restitution following Injury by Hypertonic NaCl in Bullfrog Stomach in vitro
Authors: Furukawa Osamu , Kume Eisuke , Sugamoto Shinich , Kawauchi Shoji , Takeuchi Koji
Published: April 2003

Background: The antiulcer drug ecabet 2Na (12-sulfodehydroabietic acid disodium salt) exhibits a gastroprotective activity, mainly through a local action, involving endogenous prostaglandins (PGs) and nitric oxide (NO). In the present study, we examined the effect of ecabet on the epithelial restitution of the bullfrog gastric mucosa in vitro following injury by hypertonic NaCl. Methods: Bullfrog fundic mucosa was mounted in an Ussing chamber. The tissue injury was induced by exposure of the mucosa to 1.25 M NaCl for 5 min, and transmucosal potential difference (PD) and electrical resistance (R) were measured during a 4-hour test period. Ecabet (3–30 mg/ml) was added to the luminal solution for 10 min before or after NaCl, while 16,16-dimethyl PGE2 (dmPGE2: 1× 10–6 M) or NOR-3 (a NO donor: 1 × 10–4 M) was added to the nutrient solution 10 min before NaCl. Results: Mucosal application of 1.25 M NaCl caused an immediate reduction of PD and R, followed by a gradual normalization, reaching about 70% of the pre-exposure levels within 4 h. Ecabet, added before NaCl, significantly expedited the recovery of PD and R in a concentration-dependent manner; this effect was mimicked by posttreatment with ecabet and significantly mitigated by prior addition of indomethacin (1 × 10–5 M) or NG-nitro-L-arginine methyl ester (L-NAME: 1 × 10–3 M). The epithelial restitution was also significantly promoted by serosal application of either dmPGE2 or NOR-3. The mucosal exposure to ecabet significantly increased the luminal release of PGE2 and NO metabolites, the effects being attenuated by indomethacin and L-NAME, respectively. The mucous secretion was increased by ecabet as well as dmPGE2 and NOR-3, and the effect of ecabet was significantly suppressed by both indomethacin and L-NAME. The inhibitory effects of L-NAME on the ecabet action were all significantly antagonized by concurrent addition of L-arginine. Conclusion: These results suggest that ecabet significantly expedited the restitution following gastric surface cell injury, and this action is mediated by endogenous NO as well as PGs and may be functionally associated with an increase of mucous secretion.
Gastrin-Mediated Alterations in Gastric Epithelial Apoptosis and Proliferation in a Mastomys Rodent Model of Gastric Neoplasia
Authors: Kidd Mark , Tang Laura H. , Modlin Irvin M. , Zhang Tong , Chin Kelly , Holt Peter R. , Moss Steven F.
Published: April 2003

Background/Aims: Hypergastrinemia secondary to low acid secretion is associated with gastric carcinoid formation in Mastomys. We investigated the effect of gastrin on oxyntic epithelial apoptosis and proliferation in this model. Methods: Hypergastrinemia and mucosal hyperplasia were induced by irreversible H2 receptor blockade with loxtidine. Gastrin levels were normalised in some animals by 10 days’ loxtidine withdrawal. Serum gastrin was determined by radioimmunoassay, proliferative, enterochromaffin-like cells and Bcl-2 protein family expression by immunohistochemisty, and apoptotic cells by terminal deoxyuridine nucleotide nick end labeling (TUNEL). Results: Proliferating cells were increased 4-fold in loxtidine-treated animals, and returned to normal upon loxtidine withdrawal. Enterochromaffin-like cell number increased 2-fold with loxtidine, and did not decrease after withdrawal. Apoptotic epithelial cells were located at the luminal surface and increased 1.8-fold with loxtidine, returning to control levels upon withdrawal. The ratio of proliferative to apoptotic cells was lower in the control and withdrawn groups than in the loxtidine group (0.26 ± 0.05 and 0.26 ± 0.08 vs. 0.77 ± 0.12). With hypergastrinemia, the expression of Bcl-2 and Bak was increased and Bax decreased in the middle of the gland. Conclusion: Hypergastrinemia is associated with alterations in both proliferation and apoptosis in Mastomys gastric mucosa. This may contribute to the pathogenesis of mucosal hyperplasia in this model.
Plasma Cholecystokinin, Plasma Peptide YY and Gallbladder Motility in Patients with Slow Transit Constipation: Effect of Intestinal Stimulation
Authors: Mollen Roland M.H.G. , Hopman Wim P.M. , Kuijpers Han H.C. , Jansen Jan B.M.J.
Published: April 2003

Background/Aim: Because cholecystokinin and peptide YY are gut hormones with potent effects on gastrointestinal motility, we determined whether abnormalities of cholecystokinin and peptide YY exist in slow transit constipation. Methods: Plasma concentrations of these hormones before, during and after intraduodenal infusion of a liquid meal in 21 patients with slow transit constipation were compared with the results in 8 healthy controls. Results:  Fasting levels of plasma cholecystokinin (3.1 ± 0.2 vs. 2.4 ± 0.2 pM; p = 0.02) were higher in patients. Basal plasma peptide YY (11.4 ± 1.4 vs. 8.9 ± 0.7 pM; p = 0.1) tended to be higher in patients. After the meal (60–90 min), incremental cholecystokinin (p < 0.05), but not peptide YY, was significantly higher in patients. During intraduodenal infusion of the meal (0–60 min), incremental plasma cholecystokinin (251 ± 20 pM·min) and peptide YY (1,146 ± 186 pM·min) in patients were almost similar to control values (262 ± 22 and 901 ± 166 pM·min). Gallbladder volumes before, during and after the meal were not different between the 2 groups. Gastric emptying of a solid meal was delayed in the majority of patients (12 of 18). Abnormalities of plasma cholecystokinin were observed only in patients with delayed gastric emptying. Conclusion: Plasma levels of cholecystokinin are elevated in the fasting state and decrease more slowly after stimulation, but maximum release in response to intestinal nutrients is not altered in patients with slow transit constipation. The abnormality seems to be confined to a subgroup of patients with delayed gastric emptying.
Multiple Tumors and a Novel E2F-4 Mutation
Authors: Matsubara Nagahide , Yoshitaka Tomoya , Matsuno Tsuyoshi , Ikeda Masahiko , Isozaki Hiroshi , Tanaka Noriaki , Shimizu Kenji
Published: April 2003

Defects in the DNA mismatch-repair are known to cause microsatellite instability (MSI) in hereditary nonpolyposis colorectal cancer (HNPCC) as well as sporadic colorectal cancer (CRC). We previously reported that the E2F-4 gene, which encodes an important transcription factor in cell cycle control, had frequent tumor-specific mutations at the trinucleotide coding region microsatellite (CAG)n in a subset of human sporadic CRC with MSI. We report a 65-year-old man with triple tumors in the abdomen, including colon cancer, stomach cancer, and lipoma of the retroperitoneum, with the analysis of E2F-4 mutation. We report the first case of colon cancer with a homozygous E2F-4 mutation along with a detailed analysis of other cancer related genes as well as a prognosis.
Helicobacter pylori Lipopolysaccharide Alters ECL Cell DNA Synthesis via a CD14 Receptor and Polyamine Pathway in Mastomys
Authors: Kidd M. , Tang L.H. , Schmid S. , Lauffer J. , Louw J.A. , Modlin I.M.
Published: April 2003

Chronic Helicobacter pylori infection is associated with alterations in gastric mucosal cell proliferation. Despite the recognition that bacterial lipopolysaccharide (LPS) is present in biologically active quantities in the gastric mucosa, the mechanisms by which it stimulates cells are largely unknown. We have previously established a gastric enterochromaffin-like (ECL) cell neoplasia model in the African rodent species Mastomys and identified that tumor ECL cell proliferation is associated with polyamine biosynthesis and ornithine decarboxylase (ODC) activity. In addition, we have shown that H. pylori LPS exhibits a specific mitogenic effect on naive ECL cells in vitro. The aim of this study was to evaluate whether H. pylori has a direct effect on tumor ECL cell proliferation in vitro and further to evaluate the possible molecular mechanisms for this effect. ECL cell neoplasia was generated in Mastomys by endogenous hypergastrinemia induced by H2 blockade (loxtidine 1 g/kg/day) and tumor ECL cells prepared. The DNA synthesis in 24-hour cultured tumor cells was measured by bromodeoxyuridine uptake and ODC activity by 14CO2 formation from 14C-ornithine. The putative LPS receptor, CD14, was evaluated by reverse-transcription polymerase chain reaction. Our results demonstrated: (1) H. pylori LPS (10–12 to 10–7 M) stimulated basal DNA synthesis (2.2-fold) with an estimated EC50 of 10–10 M; (2) this proliferative response correlated with an increase in ODC activity (1.4-fold, EC50 ∼10–10 M) which could be inhibited by a specific ODC inhibitor, difluoromethyl ornithine, at 10–9 M; (3) the CD14 receptor was identified in both naive and transformed ECL cells by reverse-transcription polymerase chain reaction, and (4) the effects of LPS were inhibited by blocking the CD14 receptor with its specific monoclonal antibody (1:100). Thus, H. pylori LPS appears to influence tumor ECL cell proliferation by activation of the intracellular polyamine pathway and ODC activity via a CD14 receptor on the ECL cell.
Tissue Transglutaminase Autoantibodies in Patients with Non-Hodgkin’s Lymphoma
Authors: Carroccio Antonio , Fabiani Elisabetta , Iannitto Emilio , Giannitrapani Lydia , Gravina Fabio , Montalto Giuseppe , Catassi Carlo
Published: April 2003

Background: Tissue transglutaminase (tTG) has recently been identified as the autoantigen recognized by endomysial antibodies in celiac disease (CD) patients and this has permitted the use of an ELISA test to detect the presence in the serum of autoantibodies specific for the diagnosis of CD. Aim: We report two cases of anti-tTG positivity in patients with non-Hodgkin’s lymphoma (NHL) without evidence of CD. Case Reports: Both patients were males aged 67 and 69 years respectively; both were hospitalized for fever and peripheral adenopathy. Lymph node histology showed an immunoblastic high-grade T-cell NHL at the IVth the stage of disease in both cases. They were included in a multicenter study on the association between CD and NHL. Serological screening for CD showed the presence of serum anti-tTG antibodies, with values within the range of those recorded in untreated CD patients in our laboratory; however, both patients had negative anti-endomysial antibodies and in both cases intestinal histology showed normal mucosa with villi and crypts of normal height and depth (villi/crypts ratio ≥2.5, within the range of normal subjects for our laboratory), and no increase in intraepithelial lymphocytes. The HLA phenotype was obtained giving the following antigens: Case 1: A 3, A 24(9), B 22, B 35, BW 6, DR 1, DR 11(5), DQ 3, DR 52. Case 2: A 2, A 3, B 51(5), B 8, BW 4, BW 6, DR B1*02, DR B1*03, DR B3*01. Both subjects were also positive for serum anti-smooth muscle antibodies and one for antinuclear antibodies. Conclusions: (1) Serum anti-tTG positivity can be found in subjects with NHL without CD and the real frequency of these ‘false positives’ must be investigated both in subjects with lymphoproliferative disorders and in patients with autoimmune diseases. (2) In patients with NHL, without CD, anti-tTG positivity may be unassociated with EmA positivity and the biological significance of this finding must be clarified.
Functional Evaluation Techniques in Mitochondrial Disorders
Authors: Argov Zohar
Published: April 2003

Most of the mitochondrial disorders affect the brain and muscle metabolism with variable degrees of impairment. The diagnostic usefulness of the following physiological and imaging methods, which also offer functional information that can be used for follow-up, is critically assessed: lactate levels, exercise testing, phosphorus magnetic resonance spectroscopy (MRS), proton MRS, functional magnetic resonance imaging, positron emission tomography, optical tissue oximetry and single photon emission tomography. Knowledge of the advantages, shortcomings and results of each method in the evaluation of mitochondrial diseases is mandatory before they can be applied to other disorders with suspected oxidative impairment.
Medial Medullary Infarction with Restricted Sensory Symptom
Authors: Kim Jong S. , Koh Jae-Young , Lee Jay H.
Published: April 2003

Sensory abnormalities in patients with medial medullary infarction (MMI) usually involve half of the patient’s body and extremities. We report 3 patients with restricted sensory symptoms due to MMI. Patient 1 had sensory symptoms restricted to the contralateral foot secondary to an infarct selectively involving the ventral portion of the medial lemniscus that probably corresponds to leg-representing area. Patient 2 had restricted sensory changes over the contralateral perioral area caused by lesions predominantly involving the posterior part of the medulla that may have affected a part of the ascending trigeminal tract. Patient 3 had sensory symptoms limited to the upper part of his body and the arms (pseudosyringomyelia pattern) due to bilateral MMI that may have resulted from the ventral-dorsal difference in the severity of the lesion. These patients illustrate that restricted sensory abnormalities can occur in patients with MMI. Our MRI-clinical correlation study is consistent with the previously reported sensory topography of the medial lemniscus and the ascending trigeminal tract: the leg-representing area is located ventrally in the medial lemniscus whereas the perioral-representing area is situated most medially in the ascending trigeminal tract.
Combined Immunoglobulin and Azathioprine in Multiple Sclerosis
Authors: Kalanie Hossein , Tabatabai Seid Shahabbedin
Published: April 2003

In an attempt to prevent exacerbations of multiple sclerosis, immunoglobulin therapy was combined with azathioprine (AZA). Intravenous immunoglobulin (IVIG) 2 g/kg was given in divided doses over 3 consecutive days followed by monthly booster doses (0.2 g/kg) for 3 years to 38 patients with relapsing-remitting multiple sclerosis (MS). In the 34 patients who completed the trial, the relapse rate decreased (from 1.7 relapses per year to 0 during the 3-year trial period). The Kurtzke Expanded Disability Status Scale decreased from 3.4 ± 0.72 to 3.0 ± 0.70. The results suggest that combined IVIG and AZA suppress the ongoing pathologic process in relapsing-remitting MS.
Pattern of Presentation of Multiple Sclerosis in Saudi Arabia: Analysis Based on Clinical and Paraclinical Features
Authors: Daif AbdulKader , Al-Rajeh Saad , Awada Adnan , Al Bunyan Muneera , Ogunniyi Adesola , AbdulJabar Mohammad , Al Tahan AbdulRahman
Published: April 2003

We studied 89 MS patients comprising 38 males and 51 females seen over a 10-year period. The hospital frequency was 25/100,000 patients. The diagnosis was mainly clinical and was supported by neuroimaging, cerebrospinal fluid analysis and neurophysiological tests. Sixty-five patients (73%) were Saudis and the peak age of onset was in the third decade. Fifty-two patients (58.4%) had clinically definite MS, 17 (19.1%) had laboratory-supported definite MS, 15 (16.9%) were clinically probable MS cases and the remaining 5 (5.6%) had laboratory-supported probable MS. The mean age at onset of Saudi patients (25.9 years) was lower than that of the non-Saudis (29.4 years; p < 0.001). Involvement of the pyramidal system was the commonest mode of presentation. The clinical course was relapsing-remitting in 60.7%, progressive-relapsing in 20.2% and primary progressive in 19.1%. The number of systems involved was significantly associated with the duration of disease (p < 0.001). The demographic features and the variability of clinical presentation of Saudi MS patients is similar to the results from neighbouring countries. Combination of clinical features and paraclinical tests is essential for accurate determination of extent of dissemination and for unmasking clinically silent lesions.
Thiopental in CSF and Serum Correlates with Prolonged Loss of Cortical Activity
Authors: Stover John F. , Lenzlinger Philipp M. , Stocker Reto , Morganti-Kossmann Maria C. , Imhof Hans-Georg , Trentz Otmar , Kossmann Thomas
Published: April 2003

Barbiturate coma is initiated in brain-injured patients whenever elevated intracranial pressure remains unresponsive to other therapeutical strategies. However, barbiturates alter cortical activity resulting in difficulties in clinical evaluation. Therefore, we investigated the impact of long-term thiopental administration on responsiveness to exteroceptive stimuli in relation to pharmacokinetics of thiopental in CSF and serum. Long-term infusion increases thiopental levels which remain elevated for 6 and 9 days in CSF and serum, respectively, after termination of its administration. Prolonged unresponsiveness to exteroceptive stimuli correlates with persisting thiopental in CSF and serum. Thus, quantitative analysis of thiopental in serum becomes indispensable in predicting the length of drug-induced neurological impairment and in avoiding misinterpretation of the neurological status.
Pilomotor Seizures
Authors: Yu Hsiang-Yu , Yen Der-Jen , Yiu Chun-Hing , Chung Wen-Wuh , Lirng Jiing-Feng , Su Ming-Shung
Published: April 2003

We report pilomotor seizures in two patients who had piloerection or gooseflesh spreading in a pattern like the ‘Jacksonian march’, confined ipsilaterally to the lesion side. The first patient presented this in conjunction with complex partial seizures. Left anterior temporal lobectomy abolished pilomotor and other seizures. Pathological study demonstrated hippocampal sclerosis. A meningioma near the left sphenoid region, incompletely removed, is the likely cause of pilomotor seizures in the second patient. Carbamazepine reduced these attacks. To our knowledge, hippocampal sclerosis and meningioma have never been linked to pilomotor seizures.
Is Excessive Daytime Sleepiness with Periodic Leg Movements during Sleep a Specific Diagnostic Category?
Authors: Nicolas A. , Lespérance P. , Montplaisir J.
Published: April 2003

Thirty-four patients who presented with excessive daytime sleepiness (EDS) and who showed an elevated number of periodic leg movements during sleep (PLMS) were studied. None of these patients reported other symptoms or presented sleep laboratory manifestations of narcolepsy or of breathing disorders during sleep. A diagnosis of restless leg syndrome, head trauma or a past history of psychopathology or infectious diseases known to cause EDS were also ruled out. In addition, none of the patients reported a history of drug or alcohol abuse, chronic sleep deprivation or irregular sleep-wake schedule and none were taking medications known to influence sleep at the time of the study. Results of the present study showed no correlation between PLMS index and poor sleep efficiency or daytime sleepiness as measured by the multiple sleep latency test (MSLT). However, a significant negative correlation was found between sleep efficiency at night and the mean sleep latency on the MSLT. These results suggest not only that PLMS and nocturnal sleep disruption are not the primary cause of EDS, but that these sleepy patients have a high propensity to sleep both at night and during the daytime. Therefore, the presence of PLMS during nocturnal sleep recording should not preclude the diagnosis of idiopathic hypersomnia.
Transient and Long-Term Feeding by Means of Percutaneous Endoscopic Gastrostomy in Neurological Rehabilitation
Authors: Fertl Elisabeth , Steinhoff Nikolaus , Schöfl Rainer , Pötzi Regina , Doppelbauer Andreas , Müller Christian , Auff Eduard
Published: April 2003

In 28 patients of a neurological rehabilitation unit of a hospital the use of enteral nutrition via percutaneous endoscopic gastrostomy (PEG) tubes was reviewed. During a total observation period of 5,172 days no life-threatening complications occurred. Minor complications were observed in 12 patients (43%) in the first 2 weeks after the insertion and in 5 patients (18%) afterwards. The nutritional status stabilized in all subjects. Transient PEG feeding was performed in 11 patients (39%) with a mean duration of 150 days. We conclude that hesitation in the application of PEG feeding in neurological rehabilitation should be abandoned. The timing and monitoring of PEG feeding in patients undergoing neurological rehabilitation for acute remitting neurological disorders is discussed.
Motor Perseverations: A Function of the Side and the Site of a Cerebral Lesion
Authors: Annoni Gian-Maria , Pegna Alan J. , Michel Christoph M. , Estade Miguel , Landis Theodor
Published: April 2003

Motor perseverations are commonly thought to be a sign of frontal lobe lesions, although they may also occur following lesions outside the frontal lobes. Moreover, differences in the type and frequency of motor perseverations between the two cerebral hemispheres have been suggested. Recurrent perseverations (repetition of a previous response to a subsequent stimulus) and continuous perseverations (abnormal prolongation of a current activity) are two different aspects of motor intentional disorders. The former have been associated with left hemispheric lesions, and the latter with right hemispheric lesions. To test this hypothesis, we examined 42 patients with single cerebral lesions of different locations: 22 right hemispheric (7 frontal and 15 extrafrontal) and 20 left hemispheric lesions (8 frontal and 12 extrafrontal), and healthy controls with a graphic task, allowing for analysis of these two types of motor perseverations. We found that (i) both types of perseverations increased significantly for all groups of patients compared to normal controls, except for recurrent perseverations in patients with right posterior lesions, (ii) there was no significant dissociation between the type of perseverations and the side of lesions, and (iii) there was a significant interaction between the type of perseveration, frontal versus extrafrontal location, and the side of a lesion, which is based on the tendency for recurrent perseverations to be increased in left posterior and right frontal lesions, and decreased in left frontal and right posterior lesions, as compared to continuous perseverations. These findings cast doubt about the predominant role of the frontal lobes for motor perseverations, but support the idea of hemispheric specialization in motor control which is, however, more complex than previously thought.
Lesion Localization in Developing Poststroke Hand Dystonia
Authors: Karşidaǧ; Sibel , Özer Feriha , Şen Aysu , Arpacı Baki
Published: April 2003

Reports of 9 cases with hand dystonia due to stroke are described. The site of the lesion was found to be parietothalamic in 1 patient, posterolateral thalamic in 5 patients, dorsal thalamic in 2 patients and medial thalamic in 1 patient as defined by computerized tomography or magnetic resonance imaging. In addition to the hand dystonia, hemiballism was noted in 1 case, hemichorea in 2 cases, action tremor in 3, anxiety in 3 and pain in 2 cases. The time lapse from the stroke to the manifestation of dystonia was 1 month to 2 years.
Acute Disseminated Encephalomyelitis following Pontiac Fever
Authors: Spieker S. , Petersen D. , Rolfs A. , Fehrenbach F. , Kuntz R. , Seuffer R.H. , Fetter M. , Dichgans J.
Published: April 2003

We report the case of a 35-year-old woman who developed headache and psychosis and gradually became comatose within 3 weeks after a flu-like infection. MRI revealed bifrontal demyelination consistent with acute disseminating encephalomyelitis (ADEM). Two different cerebrospinal fluid samples were positively tested for Legionella cincinnatiensis by direct sequencing of a PCR-amplified Legionella-specific fragment. This result made it possible to interpret the initial symptoms as Pontiac fever. We think it most likely that this is a case of ADEM following the very rare situation of a systemic infection with L. cincinnatiensis. A review of the literature on Legionella-associated encephalopathy suggests that some of these cases may also have had ADEM.