bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of the Substrate on the Reproducibility of the Hydrogen Breath Test to Measure the Orocecal Transit Time
Authors: Casellas F. , Malagelada J.-R.
Published: April 2003

Background: The H2 breath test is widely used for the measurement of the orocecal transit time (OCTT). However, its clinical applicability is limited by its suboptimal reproducibility. Aim: To investigate whether changes in the substrate for the H2 breath test improve its reliability for the measurement of the OCTT. Methods: 72 consecutive patients referred for measurement of the OCTT were studied. The breath test was performed twice, on consecutive days. One group of patients (‘lactulose + water’ group) received lactulose 13.3 g in water both days. Another group (‘lactulose + diet’) received lactulose 13.3 g in a liquid meal of 400 kcal. A third group (‘lactulose-lactitol’) received 13.2 g of lactulose the first day and 10 g lactitol the following day. The fourth group (‘lactitol + water’) received lactitol 10 g in water both days. Alveolar breath was sampled every 10 min for the next 3 h for H2 chromatography. Results: OCTT in the first and second day test for the groups ‘lactulose + water’, ‘lactulose + diet’ and ‘lactitol + water’ were similar. In these three groups, the values obtained on the first and second day did not differ from 0 and were also significantly correlated. However, the correlation and the mean coefficient of variation were better in group ‘lactulose + water’ than in the groups ‘lactulose + diet’ and ‘lactitol + water’. In group ‘lactulose-lactitol’ the results on both days were significantly correlated although the delta between matched values was different from 0 (p = 0.03). Conclusion: The meal substrate influences the variability of the OCTT. However, reproducibility of the test does not improve with the addition of a liquid meal.
Subepithelial Collagen Thickening in the Colon: Report on a Series of 23 Patients
Authors: Loffeld R.J.L.F. , Balk A.T.
Published: April 2003

Background: To investigate the prevalence of collagenous colitis in patients presenting with diarrhoea. Methods: Descriptive retrospective study in consecutive patients under study because of chronic diarrhoea. Results: In a 4.5-year period 23 consecutive patients had histological signs of thickening of the subepithelial collagen band in the colon. There was a female predominance: 19 women versus 4 men, mean age 60 years (range 33–83). The stool frequency was 1–13 stools daily. Indicanuria was present in 9 patients. The patients were divided into 3 groups: those with definite collagenous colitis (n = 11; thickness of the collagen band of more than 10 µm); those with indefinite collagenous colitis (n = 8; thickness between 3 and 10 µm), and those with a collagen band between 1 and 3 µm (n = 4). During a mean follow-up of 20 months (range 13–36), 7 patients had waxing and waning episodes of diarrhoea, 11 showed spontaneous waning of complaints and a lower stool frequency. The 9 patients with indicanuria did well after a course of tetracyclin 250 mg t.i.d., but all cases relapsed during follow-up. Conclusion: It is concluded that thickening of the collagen band and collagenous colitis are not as unusual as usually thought.
Oxidative Stress Affects Pancreatic Proteins during the Early Pathogenesis of Rat Caerulein Pancreatitis
Authors: Reinheckel Thomas , Prause Juliane , Nedelev Barbara , Augustin Wolfgang , Schulz Hans-Ulrich , Lippert Hans , Halangk Walter
Published: April 2003

Rats received up to four subcutaneous injections of caerulein (20 µg/kg) in hourly intervals to induce a mild edematous pancreatitis. A single dose of caerulein resulted in significant oxidative modification of proteins in pancreatic homogenates as compared to saline-injected controls (p < 0.01). Repeated injections of the secretagogue were unable to induce a further increase in modified proteins. Protein oxidation preceded the formation of the lipid peroxidation product malondialdehyde as well as edema and the increase in serum amylase by 1–2.5 h. Western blotting for oxidatively modified proteins confirmed the results of the quantitative measurements and did not reveal individual, selectively modified proteins. These findings indicate that oxidative stress and oxidative protein modification are very early events in the initial period of caerulein pancreatitis. This may explain the poor success rate of most studies that administered antioxidants therapeutically during or after initiation of pancreatitis.
Intestinal Leiomyosarcoma and Gastroparesis Associated withvon Recklinghausen’s Disease
Authors: Bernardis V. , Sorrentino D. , Snidero D. , Avellini C. , Paduano R. , Beltrami C.A. , Digito F. , Bartoli E.
Published: April 2003

The rare association between intestinal leiomyosarcoma, von Recklinghausen’s disease (type-1 neurofibromatosis) and gastroparesis is described. A 20-year-old male, diagnosed 12 years earlier as having pelvic von Recklinghausen’s disease, presented with nausea and vomiting. A gastric scintigraphy demonstrated an extremely slow gastric emptying time in the absence of obvious causes for gastroparesis. A small ileal leiomyosarcoma was later found and removed by surgery. The latter was followed by a marked improvement in the clinical condition of the patient.
Evidence of Transient IgA Anti-Endomysial Antibody Positivity in a Patient with Graves’ Disease
Authors: Carroccio A. , Custro N. , Montalto G. , Giannitrapani L. , Soresi M. , Notarbartolo A.
Published: April 2003

Background: Anti-endomysial antibodies (EmA) have been shown to have a high specificity and sensitivity in celiac disease (CD) diagnosis, and their use is considered effective in improving the diagnostic accuracy of CD screening. Aims: To report the clinical details of transient IgA EmA positivity in a patient with Graves’ disease. Methods: We screened 48 patients (7 males, age range 19–79, median 58.3 years) for CD. They were hospitalized for thyroid disorders (30 patients had autoimmune hypothyroidism and 18 had Graves’ disease with clinical hyperthyroidism associated with diffuse goitre). CD screening was carried out on all patients by assaying serum anti-gliadin antibodies (AGA) and EmA. Results: None of the 48 patients in our study were positive for IgA and/or IgG-class AGA and none showed IgA deficiency. Only 1 patient was positive for EmA; however, intestinal biopsy in this subject was normal both when thyroiditis was first diagnosed and subsequently after 2 and 3 years. Furthermore, EmA became negative after 2 years. New gastroenterological investigations performed 3 years after the diagnosis confirmed the normal intestinal histology and absorption capacity. Moreover, AGA, EmA and tissue transglutaminase antibodies were negative. Conclusions: This study underlines the possibility of transient EmA positivity without any signs of CD in patients with autoimmune thyroid disorders.
Effects of Tropisetron, a 5-HT3 Receptor Antagonist, on Proximal Gastric Motor and Sensory Function in Nonulcer Dyspepsia
Authors: Klatt Stefan , Böck Wolfgang , Rentschler Jochen , Beckh Karlheinz , Adler Guido
Published: April 2003

Background: Visceral hypersensitivity is claimed to be involved in the pathogenesis of nonulcer dyspepsia (NUD). In a double-blind crossover study, we evaluated the effects of tropisetron, a 5-HT3 receptor antagonist, on gastric accommodation, reflex relaxation, and sensitivity in NUD patients. Methods: Eight patients and 10 healthy controls received placebo or 5 mg tropisetron on separate days. On each day, gastric accommodation and relaxation were investigated using a gastric barostat. The perception during gastric distension and relaxation was scored by a verbal perception score. Results: Under both medications, gastric accommodation and postprandial gastric reflex relaxation were not impaired in the NUD patients. The visceral perception was increased in the NUD patients and not substantially influenced by tropisetron. Conclusions: Tropisetron does not influence gastric accommodation, reflex relaxation, or gastric sensitivity in NUD patients and healthy controls.
Ethanol Feeding Aggravates Morphological and Biochemical Parameters in Experimental Chronic Pancreatitis
Authors: Puig-Diví Valentí , Molero Xavier , Vaquero Eva , Salas Antonio , Guarner Francisco , Malagelada Jean-R.
Published: April 2003

Background and Aims: Instillation of trinitrobenzene sulfonic acid (TNBS) into the rat pancreatic ducts induces morphological changes resembling human chronic pancreatitis. In humans, alcoholism is commonly associated with chronic pancreatitis, but ethanol feeding fails to induce pancreatitis in experimental animals. We hypothesized that ethanol would manifest its pathogenetic effects on a duct-injured pancreas. Methods: Chronic pancreatitis was induced in rats by instillation of TNBS into pancreatic ducts. Thereafter, rats were fed a normal chow diet with or without ethanol supplementation. Control rats received vehicle and a normal diet. A separate group of vehicle-treated rats were also fed with ethanol. At 2 and 4 weeks pancreata were excised and processed for morphological examination or for biochemical assays. From crude homogenates, protein and hydroxyproline were quantified. After sonication, homogenates were also assayed for amylase and DNA. An oral glucose tolerance test was performed on the fourth week. Results: TNBS induced chronic fibrogenic pancreatitis that was associated with a reduction in pancreatic weight, DNA, protein and amylase as compared to control rats. Ethanol feeding to TNBS-treated animals slowed weight gain, increased fasting glucose and impaired glucose tolerance test. Larger areas of gland atrophy were observed with a striking disruption of the normal architecture of the islets. Ethanol accelerated pancreatic involution and collagen deposition as measured by total amylase, protein, DNA and hydroxyproline content. Conclusions: In TNBS chronic pancreatitis, active fibrogenesis is associated with progressive atrophy of glandular elements. Morphological and biochemical parameters are aggravated by sustained ethanol intake.
Localization of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases-2 in Normal Human and Rabbit Stomachs
Authors: Tatsuguchi Atsushi , Fukuda Yuh , Ishizaki Masamichi , Yamanaka Nobuaki
Published: April 2003

Background/Aims: Matrix metalloproteinases (MMPs) are endopeptidases that degrade extracellular matrix and are involved in the pathogenesis of gastrointestinal ulcer and cancer along with tissue inhibitors of metalloproteinases (TIMPs). The purpose of this study is to examine their localization and functions in the normal stomach. Methods: We examined the localization of MMP-1, MMP-2, MMP-9 and TIMP-2 in normal human and rabbit stomachs by light- and electron-microscopic immunohistochemistry and Western blotting, and the enzymatic activities of MMP-2 and MMP-9 by gelatin zymography. Results: Immunohistochemistry revealed their localization in parietal cells, and surface and foveolar epithelial cells. Electron-microscopic immunohistochemistry of parietal cells showed immunolabeling of MMP-2 and TIMP-2 in the cisternae of the rough endoplasmic reticulum, and that of MMP-1 and MMP-9 in tubular structures in their cytoplasm. Western blotting revealed that the densities of MMP-2 and MMP-9 bands were higher for the fundic gland region than for the pyloric gland region. Gelatin zymography revealed that tissue extracts of the fundic gland region exhibited higher enzymatic activity of MMP-2 and MMP-9 than those of the pyloric gland region. Conclusion: Normal rabbit and human stomachs contain MMP-1, MMP-2, MMP-9, and TIMP-2 and these are mainly localized in, and synthesized by parietal cells.
Interaction of Putrescine with Nuclear Oligopeptides in the Enterocyte-Like Caco-2 Cells
Authors: Pignata Sandro , Di Luccia Aldo , Lamanda Roberto , Menchise Antonella , D’Agostino Luciano
Published: April 2003

Intestinal cells are able both to synthesize and take up putrescine, the main compound of the metabolic polyamine pathway. Polyamine binding to nuclear macromolecules is thougth to modulate DNA synthesis and transcription. Our aim was to study the fate of putrescine when taken up from the medium in the enterocyte-like Caco-2 cells and to analyze its binding to nuclear proteins. After having incubated the cells with 14C-putrescine (0.8 μM), during cell replication and differentiation, the nuclei were separated by sequential centrifugations in a sucrose gradient. About 20% of the putrescine taken up by Caco-2 cells resulted in the nuclei in both proliferating and differentiated cells. The binding of polyamines to nuclear proteins was studied on nuclear extracts, separated by both alkaline polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) and gel permeation chromatography (GPC). No radioactivity was found in nuclear protein extracts when using the SDS-PAGE method. Conversely, in replicating cells, GPC showed that the greatest amount of radioactivity was present in the nuclear peaks corresponding to oligopeptides with a molecular weight of 4,800–8,000 daltons. High-performance liquid chromatography analysis showed the presence of putrescine and spermidine in the 8,000-dalton protein peak, whereas in the 4,800-dalton peak spermine was found in addition to putrescine. The radioactive count in the HPLC separated polyamines showed that a small percentage of the radioactivity present in the 8,000 and 4,800-dalton GPC peaks was linked to spermine and spermidine, suggesting an interconversion of the supplemented putrescine. Conversely, in differentiated cells, the nuclear oligopeptides did not reveal any radioactivity or any polyamines, suggesting that the binding of polyamines to nuclear oligopeptides is exclusively concerned with replicating cells.
Stimulatory Effect of Nitric Oxide on Bicarbonate Secretion in Bullfrog Duodenums in vitro
Authors: Furukawa Osamu , Kitamura Motohiro , Sugamoto Shinichi , Takeuchi Koji
Published: April 2003

The effect of nitric oxide (NO) on HCO–3 secretion was examined in vitro using an isolated preparation of bullfrog duodenum. The tissue was bathed in unbuffered Ringer’s solution gassed with 100% O2 on the mucosal side and HCO–3 Ringer’s solution gassed with 95% O2–5% CO2 on the serosal side. The HCO–3 secretion was measured by the pH-stat method using 2 mmol/l HCl as the titrant to keep the mucosal pH at 7.4. (±)-(E)-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamine (NOR3) was used as a NO donor and added to the serosal solution. To analyze the NOR3 action on HCO–3 secretion, the effects of dibutyryl adenosine-3′,5′-cyclic monophosphate (dbcAMP), dibutyryl guanosine-3′,5′-cyclic monophosphate (dbcGMP), methylene blue, and indomethacin on the HCO–3 response were also examined. NOR3 (1×10–4 and 3×10–4 mol/l) caused an increase in HCO–3 secretion in a dose-dependent manner, and this effect appeared with an about 30-min time lag, reaching the level of 1.5–2.5 times greater than basal values at 1–2 h later. Both dbcAMP (1×10–3 mol/l) and dbcGMP (1×10–3 mol/l) also caused a significant increase in HCO–3 secretion in bullfrog duodenums in vitro, although the onset of the HCO–3 response to dbcGMP was delayed as compared to the former. The stimulatory action of NOR3 on duodenal HCO–3 secretion was significantly attenuated by methylene blue (5×10–5 mol/l) and indomethacin (1×10–5 mol/l), the latter also inhibiting the HCO–3 response to dbcGMP. The release of prostaglandin E2 in the serosal solution was significantly increased after addition of NOR3 (3×10–4 mol/l) and dbcGMP (1×10–3 mol/l) in an indomethacin-sensitive manner. These results suggest that the NO donor increases duodenal HCO–3 secretion in vitro, and this action of NO donor is cGMP-dependent and mediated by endogenous prostaglandins. Duodenal HCO–3 secretion may be regulated locally by NO/cGMP in addition to prostaglandin/cAMP.
Noninvasive 13C-Octanoic Acid Breath Test Shows Delayed Gastric Emptying in Patients with Amyotrophic Lateral Sclerosis
Authors: Toepfer M. , Folwaczny C. , Lochmüller H. , Schroeder M. , Riepl R.L. , Pongratz D. , Müller-Felber W.
Published: April 2003

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor neurons. However, ALS has been recognized to also involve non-motor systems. Subclinical involvement of the autonomic system in ALS has been described. The recently developed 13C-octanoic acid breath test allows the noninvasive measurement of gastric emptying. With this new technique we investigated 18 patients with ALS and 14 healthy volunteers. None of the patients had diabetes mellitus or other disorders known to cause autonomic dysfunction. The participants received a solid standard test meal labeled with 13C-octanoic acid. Breath samples were taken at 15-min intervals for 5 h and were analyzed for 13CO2 by isotope selective nondispersive infrared spectrometry. Gastric emptying peak time (tpeak) and emptying half time (t½) were determined. All healthy volunteers displayed normal gastric emptying with a mean emptying t½ of 138 ± 34 (range 68–172) min. Gastric emptying was delayed (t½ > 160 min) in 15 of 18 patients with ALS. Emptying t½ in ALS patients was 218 ± 48 (range 126–278) min (p < 0.001). These results are compatible with autonomic involvement in patients with ALS, causing delayed gastric emptying of solids and encouraging the theory that ALS is a multisystem disease rather than a disease of the motor neurons only.
Subacute Liver Failure Induced by Phenprocoumon Treatment
Authors: Mix H. , Wagner S. , Böker K. , Gloger S. , Oldhafer K.J. , Behrend M. , Flemming P. , Manns M.P.
Published: April 2003

We report on a 39-year-old woman suffering from deep venous thrombosis due to a heterozygous factor-V-Leiden mutation with resistance to activated protein C. Four months after beginning oral anticoagulation, generalized jaundice appeared. Subsequently, subacute liver failure developed necessitating an orthotopic liver transplantation. Histopathology showed features of extensive liver cell necrosis without evidence of a substantial inflammatory infiltrate. Based on histopathology and exclusion of other liver diseases, phenprocoumon-induced liver failure was diagnosed. Five months after transplantation the patient is well with normal liver function tests. Because of the widespread use of oral anticoagulants, not only bleeding complications but also hepatotoxicity should be considered in therapy supervision.
40- to 100-kD Protein(s) of Helicobacter pylori Stimulate DNA Synthesis in Epithelial Cell Lines without Affecting Apoptosis
Authors: Neopikhanov Vadim , Samali Afshin , Wreiber Karin , Engstrand Lars , Uribe Andrés
Published: April 2003

Background: Previous in vitro studies have demonstrated that water extracts and sonicates of Helicobacter pylori increase DNA synthesis in a small intestinal epithelial cell line. The aim of this study was to identify mitogenic factor(s) in a water extract of a H. pylori strain and to examine their effects on DNA synthesis and apoptosis in vitro. Methods: IEC-6 and FHs 74 cells were incubated for 24 h with different dilutions of a water extract of H. pylori (cytotoxic strain 88–23) or with 6 protein fractions obtained by gel filtration. Cells were labeled with tritiated thymidine and processed for autoradiography. DNA synthesis was evaluated by the labeling index (LI%). The proportion of IEC-6 cells undergoing apoptosis and/or necrosis was evaluated by flow cytometry using fluorescein isothiocyanate (FITC)-labeled annexin-V and propidium iodide. In vitro caspase activity was also determined as an alternative method for detection of apoptosis. Results: The water extract of H. pylori 88-23 markedly increased DNA synthesis in both epithelial cell lines (p < 0.01). A marked stimulation of DNA synthesis was also observed in IEC-6 cells incubated with fraction II- containing proteins of a molecular weight ranging between 40 and 100 kD (p < 0.01). A lesser stimulation of DNA synthesis was observed in cells incubated with higher concentrations of the other protein fractions (p < 0.01). Neither the water extract of H. pylori 88-23 nor the protein fraction II (40–100 kD) induced apoptosis in IEC-6 cells. Conclusion: A water extract of H. pylori 88-23 and a protein fraction containing proteins with molecular weights of 40–100 kD stimulate DNA synthesis in a rat and human small intestinal cell line. Apoptosis was unaffected by the water extract and by protein fraction II, which indicate that the H. pylori-derived mitogen(s) have the capacity to directly enhance epithelial cell proliferation in vitro.
Comparison of the 1-Gram 14C-D-Xylose Breath Test and the 50-Gram Hydrogen Glucose Breath Test for Diagnosis of Small Intestinal Bacterial Overgrowth
Authors: Stotzer Per-Ove , Kilander Anders F.
Published: April 2003

Background/Aims: Culture of small bowel aspirate is the most direct method and the gold standard for diagnosing small intestinal bacterial overgrowth. However, cultures are cumbersome and fluoroscopy is required for obtaining aspirate. Therefore, different breath tests such as the xylose breath test and the hydrogen breath test have been developed. There is no general agreement as to which test is to be preferred. In the only previous direct comparison between these two tests an advantage for the 1-gram-14C-D-xylose breath test was found. The aim of the study was to compare the 50-gram glucose hydrogen breath test and the 1-gram 14C-D-xylose breath test in relation to results of cultures of small bowel aspirate. Methods: Forty-six consecutive patients, mean age 57 (range 27–87) years, 12 men and 34 women, were included because of suspicion of small intestinal bacterial overgrowth. After small bowel aspiration, all patients received a solution of 1 g xylose, labelled with 50 µg 14C-D-xylose, and 50 g glucose dissolved in 250 ml water. The concentration of breath hydrogen was analyzed every 15 min for 2 h and 14CO2 was analyzed every 30 min for 4 h. A positive hydrogen breath test was defined as a rise in hydrogen concentration of 15 ppm. A positive xylose test was defined as an accumulated dose 4.5% after 4 h. Two definitions for a positive culture were used, either growth of 105 colonic-type bacteria/ml or growth of 105 bacteria/ml of any type. Results: Twenty-four patients had growth of 105 bacteria, of whom 10 had growth of 105 colonic-type bacteria in small bowel aspirate. Twenty-two patients had no significant growth. The hydrogen breath test and the xylose breath test had a sensitivity for growth of 105 bacteria of 58 and 42%, respectively. For growth of 105 colonic-type bacteria the sensitivity was 90% for the hydrogen breath test and 70% for the xylose breath test. The specificity was similar for the two tests. Conclusion: Although no significant difference between the two tests was found, there was a tendency in favor of the 50-gram glucose hydrogen breath test. The simplicity in combination with high sensitivity makes the hydrogen breath test suitable as a screening method to select patients for further investigation.
Evidence of Abnormal Esophageal Motility in Syndrome X by Radionuclide Esophageal Transit Test
Authors: Kao C.H. , Hsieh J.F. , Tsai C.S. , Ho Y.J. , Lee J.K.
Published: April 2003

In 30 patients with syndrome X, esophageal motility was evaluated by radionuclide esophageal transit test (RETT). Esophageal motility measurements included esophageal mean transit time (MTT), residual fraction (RF), and retrograde index (RI). In comparison with 25 age- and sex-matched healthy volunteers, 66% of the patients with syndrome X had abnormal RETT findings including 50% of cases with longer MTT, 50% of cases with higher RF, and 33% of cases with higher RI. In addition, the mean values of MTT, RF, and RI in patients with syndrome X were significantly higher than those of healthy volunteers. We conclude that abnormal esophageal motility occurred in a large portion of syndrome X patients based on an simple and noninvasive RETT.
Liver Transplantation in Primary Biliary Cirrhosis: Risk Assessment and 11-Year Follow-Up
Authors: Rust Christian , Rau Horst , Gerbes Alexander L. , Pape Gerd R. , Haller Mathias , Krämling Hans-Jörg , Schildberg Friedrich W. , Paumgartner Gustav , Beuers Ulrich
Published: April 2003

Background/Aims: Liver transplantation (LTx) is the only established treatment in patients with end-stage primary biliary cirrhosis (PBC). Although short-term survival after LTx in this group of patients is usually good, few data exist on the long-term survival. The optimal timing of transplantation is difficult. Thus, the aims of this study were to assess the long-term survival of patients with PBC after LTx and to identify potential predictive factors for a positive outcome. Methods: Survival of 28 patients with PBC who underwent LTx between 1985 and July 1999 in a single center was studied by Kaplan-Meier analysis and was compared to predicted survival without LTx using established prognostic models for PBC, the Mayo and European risk scores. Potential prognostic parameters obtained before LTx were tested for correlation to survival. Rates of bone fractures as markers of hepatic osteodystrophy were compared before and after LTx. Results: Median follow-up after LTx was 90 months with a maximum of 140 months. Actuarial survival of patients with PBC was 89% after 1, 5, and 10 years and was significantly better than estimated survival without LTx after 1–7 years as calculated by the Mayo and European risk scores. Of several parameters tested, only serum bilirubin and the prognostic scores, but no other liver function tests obtained immediately prior to transplantation were significantly correlated with survival after LTx. The duration of intensive care after LTx was not associated with any parameters obtained before LTx. Bone fractures were diagnosed in 43% of patients of whom the vast majority were osteopenic before LTx as determined by osteodensitometry. Conclusion: Long-term survival of a well-defined group of patients with PBC was excellent after LTx and was inversely correlated with preoperative serum bilirubin levels as well as Mayo and European risk scores.
Induction of Artificial Fat Maldigestion by Tetrahydrolipstatin Assessed by the 13C-Hiolein Breath Test in Healthy Volunteers
Authors: Ashraf Hasan , Hildebrand Pius , Meier Remy , Beglinger Christoph , Gyr Niklaus
Published: April 2003

Background: 13C-hiolein is a purified algal triglyceride which is synthesized with 98% of all carbon atoms of the molecule uniformly 13C-labeled. Orlistat is the new name for tetrahydrolipstatin (THL), which is a specific and potent inhibitor of gastrointestinal lipases which induces artificial fat malabsorption in humans. The aim of the present study was to use the 13C-hiolein breath test (HBT) to assess THL-induced fat malabsorption in healthy volunteers. Methods: Eight healthy volunteers of normal body weight underwent 2 study periods of 4 days of diet with or without THL 120 mg t.i.d. On day 5, a HBT was performed. 13CO2 recovery in breath samples was measured over 24 h by isotope ratio mass spectrometry. Results: The peak 13CO2 excretion occurred only after 5 h in both treatment groups with little difference during the first 4 h between the groups. THL potently reduced fat digestion and absorption with the most pronounced effect observed after 8 h: 1.1± 0.2 vs. 2.3 ± 0.3% dose in control experiments (p < 0.05). The 24-hour cumulative 13CO2 excretion was also significantly reduced by THL: 14.9 ± 2.2 vs. 28.4 ± 4.1% dose in control experiments (p < 0.05). In 6 of the 8 subjects, the cumulative 13CO2 excretion was lower with THL 120 mg t.i.d. than with placebo. Conclusion: The HBT well reflects THL-induced artificial fat maldigestion in healthy volunteers.
Local and Systemic Zymogen Activation in Human Acute Pancreatitis
Authors: Mayer Jens M. , Rau Bettina , Siech Marco , Beger Hans G.
Published: April 2003

Background: Activation of trypsinogen and phospholipase A2 is an early event in pancreatic inflammation, but little is known about zymogen activation and the severity of human pancreatitis. Methods: Using a new fluoroimmunoassay we measured trypsinogen activation peptide (TAP) and phospholipase A2 activation peptide (PROP) in plasma and ascites in 25 patients with acute pancreatitis. TAP, PROP, Pro-PROP and pancreatic PLA2-I were measured in plasma for 14 days and in pancreatic necroses, ascitic fluid and pleural effusions. Results: All 16 patients with severe acute pancreatitis (SAP) had pancreatic necrosis, 10 developed systemic complications like sepsis, pulmonary or renal failure, 6 had infected necrosis, and 4 died. All 9 patients with mild pancreatitis (MAP) survived. Plasma TAP on admission was higher in patients with SAP than in those with MAP and increased in infected necroses. It did not correlate with systemic complications. Systemic PROP was not increased in complicated courses but was significantly higher in patients with MAP than in those with SAP on admission. Pro-PROP was higher in patients with SAP than in those with MAP but was not correlated with systemic complications. Plasma pancreatic PLA2-I was increased but not different in patients with SAP and those with MAP. In patients with pancreatic necrosis, TAP and PROP were highest, while in those with post-acute pancreatic abscess, only PROP and Pro-PROP were high. In patients with pleural effusion, TAP was low and PROP/ Pro-PROP were high. Conclusion: Trypsinogen and PLA2-I activation are early events in acute pancreatitis and the activation peptides can be detected in plasma. In the pancreas, trypsinogen activation is accompanied by PLA2-I activation in patients with pancreatic necrosis. However, in our study, organ complications in SAP patients was not associated with increased plasma PROP.
Low Frequency of p16INK4a Alterations in Insulinomas
Authors: Bartsch Detlef K. , Kersting Michael , Wild Anja , Ramaswamy Annette , Gerdes Berthold , Schuermann M. , Simon Babette , Rothmund Matthias
Published: April 2003

Background/Aims: The molecular mechanisms contributing to the tumorigenesis of insulinomas are poorly understood. Disruption of the cell cycle due to inactivation of the p16INK4a tumor-suppressor gene was identified in a variety of human tumors, including gastrinomas and nonfunctioning endocrine pancreatic carcinomas. In this study the role of p16INK4a in the tumorigenesis of insulinomas was evaluated. Methods: Seventeen insulinomas (14 benign, 3 malignant) were analyzed for genetic alterations in the p16INK4a tumor-suppressor gene by SSCP, PCR-based deletion and methylation-specific assays. p16 expression was determined by immunohistochemistry. Results: One malignant insulinoma showed a homozygous deletion of p16INK4a and another two benign insulinomas revealed aberrant methylation of the p16INK4a promoter region. All three tumors lacked p16 expression according to immunohistochemistry. None of the insulinomas carried intragenic p16INK4a mutations. In total, 17% of insulinomas had p16INK4a alterations. Conclusions: The p16INK4a tumor-suppressor gene contributes to tumorigenesis in only a small subset of insulinomas.
Obstructive Jaundice, Bacterial Translocation and Interdigestive Small-Bowel Motility in Rats
Authors: Nieuwenhuijs Vincent B. , van Dijk Jaap E. , Gooszen Hein G. , Akkermans Louis M.A.
Published: April 2003

Background/Aims: Translocation of gut bacteria occurs in obstructive jaundice, the underlying mechanisms are unclear. We designed this experimental study to investigate the association between interdigestive motility and the pathogenesis of bacterial translocation during biliary obstruction. Methods: Rats were fitted with jejunal myoelectrodes for the measurement of the interdigestive migrating motor complex (MMC) and with two cannulas in the proximal common bile duct (CBD) for exteriorization of biliary flow. This allowed measurement of MMCs under control conditions with an intact enterohepatic circulation and during 3 days of CBD obstruction without surgical intervention. Mesenteric lymph nodes, liver, spleen and segments of the duodenum, the jejunum and the caecum were removed for microbial culturing. Results: The MMC cycle length increased from 17.3 min before CBD obstruction to 31.9, 34.1, and 25.3 min on days 1, 2 and 3, respectively, after CBD obstruction (p < 0.05 for all days). Bacterial levels in the jejunum were significantly higher in CBD-obstructed rats than in control rats. The translocation incidence was significantly higher in rats with CBD obstruction (6/8) than in control rats (1/8). The bacterial levels in the jejunum correlated significantly with the MMC cycle length (r = 0.60, p <0.05). Conclusion: Experimental biliary obstruction is associated with disturbance of MMCs, small-bowel bacterial overgrowth and increased bacterial translocation.
Mitochondrial DNA Analysis in Ocular Myopathy
Authors: Vilarinho Laura , Santorelli Filippo M. , Cardoso Maria Luís , Coelho Teresa , Guimarães António , Coutinho Paula
Published: April 2003

We analyzed 29 patients with progressive external ophthalmoparesis (PEO) either alone or as part of a multisystem disorder. Ragged-red fibers were very abundant (10–20%) in 15 patients, and many of them were also cytochrome c oxidase-negative. Biochemical analysis of the respiratory chain showed partial defects of single or multiple complexes in 18 patients (64%). Eleven PEO patients (38%) harbored single large-scale mtDNA deletions in muscle, which averaged 5.4 kb in size and 47% in relative abundance. One PEO patient harbored the A3243G mutation (MELAS mutation) in muscle (63%). Our findings, the first reported in Portuguese patients, confirm that single large-scale mtDNA deletions are a significant cause of PEO. Although ophthalmoparesis was the main clinical feature in the majority of patients, the clinical spectrum is broad, ranging from severe encephalopathy of childhood to a milder, though disabling, muscle weakness in adults.
Type A Behavior and Stroke: High Tenseness Dimension May Be a Risk Factor for Cerebral Infarction
Authors: Kim Jong S. , Yoon Sung S. , Lee Sang I. , Yoo Hee J. , Kim Chang Y. , Choi-Kwon Smi , Lee Byung C.
Published: April 2003

Although type A behavior (TAB) has been shown to be related to coronary heart disease, the relationship between TAB and stroke was rarely investigated. We studied TAB in stroke patients with the use of the questionnaire developed by Eysenck and Fulker that has 4 subdimensions: Tenseness, Ambition, Activity, and Unrepressed. The questionnaire was administered to 224 patients with acute stroke and 100 controls. The patients were further classified as having cerebral infarction (large vessel infarction and small vessel infarction), and intracerebral hemorrhage. We found that, among the 4 subdimensions, only the Tenseness score was significantly higher in patients with cerebral infarction but not in those with intracerebral hemorrhage compared to the controls. On subgroup analysis, Tenseness score was higher in patients with large vessel infarction but not in those with small vessel infarction than in those with intracerebral hemorrhage or controls. The association of high Tenseness score with cerebral infarction (and large vessel infarction) remained significant after multiple logistic analysis adjusting various risk factors such as hypertension, diabetes mellitus, cigarette smoking and habitual alcohol drinking. Our data suggest that a high Tenseness dimension of TAB may be an independent risk factor for ischemic stroke, probably associated with atherogenesis.
Central Pathway of Taste: Clinical and MRI Study
Authors: Lee Byung-Chul , Hwang Sung-Hee , Rison Richard , Chang Gregory Youngnam
Published: April 2003

We present 3 cases of hemiageusia due to focal ischemic lesions in the brainstem. Clinical presentation with discrete localization of these lesions suggests that the central taste pathway in humans projects ipsilaterally from the solitary nucleus up to the level of the upper pontine or lower midbrain before decussation. Associated partial sensory disturbance of the face or limb with lack of evidence of medial lemniscus decussation at the upper brainstem suggests that the medial lemniscus may not directly convey taste sensation.
Histological Markers in Nasal Mucosa of Patients with Alzheimer’s Disease
Authors: Hock Christoph , Golombowski Sidonie , Müller-Spahn Franz , Peschel Oliver , Riederer Andreas , Probst Alphonse , Mandelkow Eva-Maria , Unger Jürgen
Published: April 2003

Neuropathological changes such as dystrophic neurites and the presence of abnormal τ protein in the olfactory system, including primary sensory cells and nerve fibres have previously been demonstrated in nasal mucosa tissue of patients with Alzheimer’s disease (AD). These changes were detected in autopsy-derived material from histopathologically confirmed AD cases as well as in biopsy tissue from clinical severely ill AD patients. To investigate the potential usefulness for the early diagnosis of AD, we obtained biopsy tissue from olfactory mucosa from 5 clinically mild to moderate AD patients and stained for the presence of τ or β-amyloid by immunocytochemistry using a panel of specific antibodies. No positive staining was found in any of the cases. For comparison, post-mortem olfactory tissue from AD patients with severe neuropathological changes (widespread neurofibrillary tangles and amyloid in the brain) was investigated. In these severe cases, τ immunoreactivity was found in fine nerve fibres in the lamina propria and in a few olfactory epithelial cells. These results are consistent with other reports showing that cytoskeletal changes and τ pathology in the olfactory epithelium are not primary (or specific) features of AD and may occur predominantly in late stages of the disease.
Primary Progressive Aphasia with Glial Cytoplasmic Inclusions
Authors: Molina José Antonio , Probst Alphonse , Villanueva Clara , Jiménez-Jiménez Félix Javier , Madero Santiago , Torres Nemesio , Bermejo P Félix
Published: April 2003

We report a 80-year-old woman who suffered from primary progressive aphasia for 3 years. Cranial CT and MRI studies showed moderate cerebral atrophy, more marked in the left frontal and temporal lobes, and SPECT brain scans revealed marked hypometabolism in the left frontal and temporal lobes. Neuropathologic examination of a temporal lobe biopsy demonstrated Gallyas-positive intracytoplasmic inclusions looking like fibrillary tangles and of Gallyas-positive cell processes, probably from glial cells. Glial intracytoplasmic inclusions were immunolabelled with antibodies to ubiquitin and with phosphorylion-dependent antitau antibodies, indicating the presence of hyperphosphorylated tau in the inclusions. There was only mild pathology of cortical neurons consisting in rare perikarya diffusely stained with antitau antibodies. There were no senile plaques, neurofibrillary tangles, ‘achromatic’ neurons, ballooned cells, Pick or Lewy bodies, nor microvacuoles or spongiform changes of the neuropil. The glial intracytoplasmic inclusions found in this case were similar to those found in multiple system atrophy, and differ from the cortical changes hitherto reported in primary progressive aphasia.
Death from Ischemic Stroke in the Anterior Circulation:The Contralateral Carotid Matters
Authors: Baptista Miguel Viana , van Melle Guy , Bogousslavsky Julien
Published: April 2003

Death from acute hemispheric infarction is commonly associated with stroke size, but the potential role of the internal carotid artery (ICA) in this phenomenon is poorly understood. The aim of the present study was to analyse the relation between the degree of ipsilateral and contralateral ICA stenosis, infarct type and death. We studied 2,148 first-ever stroke patients with anterior circulation infarction from the Lausanne Stroke Registry. Doppler ultrasonography with frequency spectral analysis and Duplex-scanning were performed systematically during the acute phase of stroke. The patients were divided into groups according to the degree of ipsilateral and contralateral ICA stenosis. The case fatality ratios (CFR) at hospital discharge were obtained for each group. Several clinical features including age, stroke topography, level of consciousness, limb weakness on admission, type of onset, hyperglycemia, previous transient ischemic attack, cardiac ischemia, cardiac arrhythmia and left ventricular hypertrophy were also studied. Mortality increased significantly with ipsilateral ICA stenosis: ≤50% stenosis, 2.8%, (44/1,549); >50% and ≤90% stenosis, 3.5%, (6/170); >90% stenosis, 5.6%, (24/429); p = 0.026, but not significantly with contralateral ICA stenosis. However, patients without ipsilateral ICA stenosis had significantly higher mortality when contralateral stenosis was present: 16.7% (3/18) versus 2.7% (41/1,531), p = 0.013. This corresponded to an increased frequency of strokes involving the whole middle cerebral artery territory, with impaired consciousness at onset of stroke. Patients with ipsilateral stenosis had similar CFR independently of the presence or absence of contralateral stenosis. In conclusion, patency of the contralateral ICA may be an important contributory factor of larger infarction and indirectly of stroke mortality in patients with no ipsilateral stenosis.
Acetazolamide Vasoreactivity in Vascular Dementia: A Positron Emission Tomographic Study
Authors: De Reuck J. , Decoo D. , Hasenbroekx M.C. , Lamont B. , Santens P. , Goethals P. , Strijckmans K. , Lemahieu I.
Published: April 2003

The present study investigates the vasoreactivity of the brain in patients with large infarcts and dementia (multi-infarct dementia; MID) and in patients with microangiopathy, lacunes, white matter changes and dementia (lacunar dementia; LD) using positron emission tomography (PET) and 13NH3 as regional cerebral blood flow (rCBF) tracer. In the control group, an increase in rCBF ranging from 32 to 43% was found in all brain regions after intravenous acetazolamide administration. In both the MID group and the group with multiple infarcts without dementia, moderate loss of vasoreactivity was observed in the frontal, temporal and parietal cortex compared to the control values. Vasoreactivity was severely impaired in all cerebral regions of the LD group and restricted to the thalamus in the group with lacunes and white matter changes without dementia (lacunar stroke; LS). This suggests that global loss of vasoreactivity is not a determining factor in the occurrence of MID, but might be important in LD. The present study shows that loss of the vascular reserve leading to exhausted metabolic reserve of the whole brain is one of the possible mechanisms for the occurrence of vascular dementia.
Myotonic Dystrophy in Ancient Egypt
Authors: Cattaino Giacomo , Vicario Laura
Published: April 2003

Amenhotep IV, better known as Akhenaton, the heretical pharaoh, was a king of the New Kingdom of Ancient Egypt. Statues and reliefs of him show an unhealthy man whose body has abnormal features. By studying the pictures of Akhenaton (the mummy has not yet been found), we conclude that he may have been affected by myotonic dystrophy (MD). Moreover, the available data on his family suggest that MD may have caused the end of the royal bloodline of the Eighteenth Dynasty.
No Mutation of G209A in the Alpha-Synuclein Gene in Sporadic Parkinson’s Disease among Taiwan Chinese
Authors: Hu Chaur-Jong , Sung Shing-Ming , Liu Hsing-Cheng , Chang Jan-Gowth
Published: April 2003

The role of genetics in Parkinson’s disease (PD), previously controversial, is now supported by several studies. A major breakthrough has been the discovery of a single gene defect in familial Parkinson’s disease. A single base pair change at position 209 from G to A (G209A) in the fourth exon of the α-synuclein gene has been identified in cases of familial PD. We looked for this mutation in 65 cases of sporadic PD in Taiwan Chinese patients but found none of these patients with this mutation. We conclude that mutation of G209A in the α-synuclein gene plays no role in sporadic PD among Taiwan Chinese.
Amantadine Hydrochloride Treatment in Olivopontocerebellar Atrophy: A Long-Term Follow-Up Study
Authors: Botez M.I. , Botez-Marquard T. , Elie R. , Le Marec N. , Pedraza O.L. , Lalonde R.
Published: April 2003

The efficacy of amantadine, a dopamine-releasing agent and antagonist of the N-methyl-D-aspartate glutamate receptor, was evaluated in patients with olivopontocerebellar atrophy. By contrast to an untreated control group whose terminal performance deteriorated on 8 of 8 measurements of reaction time and movement time, patients treated with amantadine for a mean duration of over 40 months had improved performances in 1 of 4 reaction time measurements and in 3 of 4 movement time measurements and remained stable on the others. These results demonstrate long-term benefits of amantadine in olivopontocerebellar atrophy-induced deficits of movement initiation and movement completion.
Escalating Immunotherapy of Multiple Sclerosis
Authors: Rieckmann P. , Toyka K.V.
Published: April 2003

The promising results of several multicenter studies during the last few years have improved the immunomodulatory treatment of multiple sclerosis (MS). The different compounds tested were shown to reduce the number of relapses and to modulate the course of disease to various extents. The transition of the results obtained in therapeutic trials into daily clinical practice is often delayed or even hampered by monetary restrictions or reluctance of the medical community to adjust their approach to new treatments. After an initial inquiry had shown that less than 50% of eligible patients received any active immunomodulating treatment, a consensus group of Austrian, German and Swiss MS societies was formed in order to prepare a report of the current treatment options in MS. The aim of this report is to present the consensus on a new concept of escalating immunotherapy in MS. Future updates of the report are planned on a yearly basis or whenever substantial new evidence becomes available.
Low-Dose Treatment of Cervical Dystonia, Blepharospasm and Facial Hemispasm with Albumin-Diluted Botulinum Toxin Type A under EMG Guidance
Authors: Rollnik Jens D. , Matzke Mike , Wohlfarth Kai , Dengler Reinhard , Bigalke Hans
Published: April 2003

Several studies support the hypothesis that low-dose botulinum toxin treatment may be as beneficial as high-dose regimen. Therefore, we studied 115 patients (aged 27–84; mean 58.0, SD = 12.9 years; 68% females, 32% males) suffering from cervical dystonia (n = 66), blepharospasm (n = 28), and facial hemispasm (n = 21) over a period of 2 years in an open label, non-controlled pilot study. Patients received low-dose treatment with botulinum toxin type A (Dysport®). The toxin was diluted in 20 ml of 0.1% albumin solution to arrive at a concentration of 25 MU/ml and injected under EMG control. Patients responded to the treatment about 1 week after injection (mean 7.3 days, SD = 4.6). The mean duration of beneficial effects was 11.7 weeks (SD = 5.6). Patients evaluated the clinical global improvement on a scale ranging from 0 to 4. For the whole population, the mean was 2.7 points (SD = 1.1). In none of the subjects could antibodies to botulinum toxin type A be detected, and only a few side effects were observed. In conclusion, low-dose therapy with botulinum toxin A merits further controlled studies.