bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of Effect of Gemifloxacin on the Steady-State Pharmacodynamics of Warfarin in Healthy Volunteers
Authors: Davy Maria , Bird Nicholas , Rost Karl Ludwig , Fuder Hermann
Published: April 2003

Gemifloxacin is a novel fluoroquinolone with a broad spectrum of activity. This double-blind, randomized, parallel-group study was designed to demonstrate the lack of effect of steady-state concentrations of gemifloxacin on the pharmacodynamic effects of warfarin. Healthy male subjects received loading doses of warfarin on days 1 and 2. The warfarin dose was freely titrated until day 10, with the aim of achieving a stable international normalized ratio (INR) for prothrombin time within the range 1.3–1.8 by day 14. On days 14–24 the dose of warfarin was fixed. On days 18–24, subjects also received 320 mg of gemifloxacin or matched placebo, once daily. Thirty-five subjects entered into and completed the co-administration phase of the study. The mean (standard deviation) baseline INR (mean of days 16–18) and INR for day 24 for gemifloxacin plus warfarin were 1.52 (0.12) and 1.46 (0.15), respectively. Corresponding values for placebo plus warfarin were 1.46 (0.11) and 1.42 (0.17). The point estimate (90% confidence interval) for the difference in day 24 INR, adjusted for baseline, between gemifloxacin and placebo was 0.02 (–0.08, 0.12), which translates to an INR (relative to placebo least squares mean of 1.43) of 1.02 (0.95, 1.09). The 90% confidence interval for the difference in INR between the gemifloxacin and placebo groups was completely contained within the 25% equivalence range. There were no changes of clinical significance in vital signs, 12-lead electrocardiogram readings or laboratory parameters for any subject during the co-administration phase of the study, and no adverse experiences relating to coagulation were reported during this period. It is concluded that the pharmacodynamic effects of warfarin are not affected by gemifloxacin, and therefore both drugs can be co-administered without dosage adjustment.
Detection of Rokitamycin-Induced Morphostructural Alterations in  Helicobacter pylori  by Atomic Force Microscopy
Authors: Braga P.C. , Ricci D.
Published: April 2003

The subinhibitory and suprainhibitory concentrations of many antibiotics are capable of interfering with the morphology of bacteria, thus disrupting the integrity of their structures and reducing bacterial virulence. Studies of this type have so far been performed using optical or scanning electron microscopes, but a new type of lens-free microscope, the atomic force microscope (AFM), has recently been introduced which is capable of investigating fine three-dimensional surface topography. The present study made use of this new technique to investigate the morphological alterations in Helicobacter pylori as a bacterial specimen exposed or not to different concentrations of rokitamycin. The produced images clearly show that AFM is a very useful tool for obtaining fine-quality three-dimensional images of bacterial morphology. The breakthrough in applying this new type of microscopy is also due to the fact that the images can be digitally collected at very high resolution in the z-axis, without the need to adopt the critical point-drying method or vacuum conditions, and without the need to coat the surface of the sample with a metal layer, a result not otherwise attainable with other microscopy techniques.
Effect of Clarithromycin on Pseudomonas aeruginosa Biofilms
Authors: Tanaka G. , Shigeta M. , Komatsuzawa H. , Sugai M. , Suginaka H. , Usui T.
Published: April 2003

Using an experimental in vitro culture system, we investigated the effect of clarithromycin on biofilm formation by a leucine-requiring Pseudomonas aeruginosa mutant strain (HU1). Biofilm formation on celldesks in a chemically defined medium was assessed by viable cell count as well as by measurement of glycocalyx production and scanning electron-microscopic observation. Cells proliferated exponentially until day 3 and remained stationary afterwards. The amount of glycocalyx, simultaneously semiquantified, showed a linear increase from day 1 to day 12. Scanning electron microscopy revealed firm biofilms on day 5. Three different concentrations of Clarithromycin (CAM) (minimum inhibitory concentration MIC 64 μg/ml) were added continuously at the early and late phases of biofilm formation, and the antibiofilm effect of CAM was evaluated by the changes in cell count and glycocalyx production. CAM was effective on biofilms at 100 μg/ml but neither at 1 nor at 10 μg/ml. It is suggested that glycocalyx production started following bacterial multiplication and continued even after the cells had entered the stationary phase to form mature biofilms. No antibiofilm effect of CAM was observed at sub-MIC.
Regulation of Apoptosis Reduction in the Cisplatin-Resistant A431 Cell Line by Bcl-2 and CPP32
Authors: Mese Hiroshi , Sasaki Akira , Alcalde Rafael E. , Nakayama Shuko , Matsumura Tomohiro
Published: April 2003

Cisplatin (cis-diamminedichloroplatinum(II), CDDP) is one of the most important chemotherapeutic agents; however, the mechanisms of resistance to this drug are still unknown. Recent reports have demonstrated that chemotherapy can induce apoptosis in some cancer cells, indicating that apoptosis may play a very important role in cancer therapy. Therefore, we used a CDDP-resistant cell line from the human epidermoid carcinoma cell line A431 to investigate whether the modulation of apoptosis influences CDDP resistance. In the CDDP-resistant cell, the cell cycle was not perturbed after CDDP treatment. DNA gel electrophoresis and ELISA of the CDDP-resistant cell showed reduced apoptosis when compared with A431 cells treated with CDDP. We determined the p53, Bcl-2, Bax and CPP32 protein levels by Western blotting. This analysis demonstrated a marked increase in Bcl-2 protein levels and a reduction in CPP32 protein levels in CDDP-resistant cells. Our results indicate that the reduction of apoptosis was one of the CDDP-resistant mechanisms, and that reduced apoptosis in CDDP-resistant cells was influenced by Bcl-2 and CPP32 proteins.
Evaluation of Neutropenic Fever: Value of Serum and Plasma Parameters in Clinical Practice
Authors: Südhoff Thomas , Giagounidis Aristoteles , Karthaus Meinolf
Published: April 2003

Treatment-related mortality due to infectious complications following potentially curable aggressive chemotherapy remains a major clinical problem. However, the diagnosis of neutropenic infections is difficult. Although it is common practice to institute empirical broad-spectrum antibiotics in neutropenic fever, liberal use of antibiotics may contribute to increasing resistance and superinfection such as systemic mycosis. Clinicians are searching for a highly specific and sensitive marker indicating early infection. Serum concentrations of several acute-phase proteins (C-reactive protein, serum amyloid A), proinflammatory cytokines (TNFα, IL-1, IFNγ, IL-6, IL-8), soluble adhesion molecules (soluble E-selectin, vascular cell adhesion molecule 1, intercellular adhesion molecule 1) and more recently procalcitonin have been investigated as to whether these may contribute to identifying infections as the cause of neutropenic fever. Unfortunately, at present, based on the small and inconsistent amount of data available from the literature one is tempted to conclude that the predictive values of all these parameters are too low to influence the clinically based initial treatment decisions in patients with neutropenic fever.
Fluconazole Inhibits Pseudohyphal Growth in Saccharomyces cerevisiae
Authors: Kontoyiannis Dimitrios P.
Published: April 2003

The ergosterol-depleting antifungal fluconazole, when given at concentrations not affecting growth, inhibited pseudohyphal growth in Saccharomyces cerevisiae, a genetically tractable fungus closely related to the human pathogen Candida albicans. These results suggest that S. cerevisiae could serve as a useful genetic system to study the morphogenetic effects induced by azoles in pathogenic yeast.
Efficacy of Amikacin, Ofloxacin, Pefloxacin, Ciprofloxacin, Enoxacin and Fleroxacin in Experimental Left-Sided Pseudomonas aeruginosa Endocarditis
Authors: Papadakis J.A. , Samonis G. , Maraki S. , Boutsikakis J. , Petrocheilou V. , Saroglou G.
Published: April 2003

The efficacies of amikacin, ofloxacin, pefloxacin, ciprofloxacin, enoxacin and fleroxacin, each as monotherapy, were evaluated in a rabbit model of induced left-sided Pseudomonas aeruginosa endocarditis. Therapy started 48 h after infection and lasted 5 days. All agents were given intramuscularly; amikacin at 7 mg/kg/12 h, and each quinolone at 35 mg/kg/12 h. All animals survived except for 1 of the group that received amikacin, and 2 of the untreated control group. No sterile vegetations were found in the untreated group and the group of fleroxacin, while 3 animals from the amikacin, ofloxacin, and enoxacin groups, and 2 from the ciprofloxacin and pefloxacin groups had sterile vegetations. All agents used significantly reduced the number of CFU per gram of vegetation versus untreated controls. Enoxacin and ciprofloxacin were equipotent and more effective than pefloxacin, ofloxacin and amikacin. Fleroxacin had a weaker activity.
Pharmacokinetics of a New Derivative of Partricin A (SPA-S-753) in Rodents
Authors: Galmozzi M.R. , Bruzzese T. , Buffa G. , Bonabello A.
Published: April 2003

Pharmacokinetics of a new semisynthetic polyene antibiotic (N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide) in the form of its diaspartate salt (code SPA-S-753) was studied in rats and mice following intravenous injection and in rats following oral administration at different dose levels. In rats the urinary and biliary recovery after intravenous administration was also determined. Rats and mice received a single intravenous injection of 1.25 and 2.5 mg/kg of SPA-S-753 (about 1–2 mg/kg of free base) or 1 mg/kg of amphotericin B as reference drug. Blood samples were obtained at 5 min to 96 h after injection. The half-lives at the elimination phase in serum were 21.3, 26.5, 10.8 h in rats and 11.7, 13.7, 19.8 h in mice, respectively, for 1.25 and 2.5 mg/kg of SPA-S-753 and 1 mg/kg of amphotericin B. The values of AUC0–∞ for SPA-S-753 were about 5 times higher in rats and twice higher in mice than those for amphotericin B. Rats received also a single oral dose of 200 or 500 mg/kg of SPA-S-753. Serum samples were obtained at 0.5–96 h after dosing. The compound is poorly absorbed by the oral route. The mean cumulative urinary recovery of SPA-S-753 at 48 h after intravenous injection of 1.25 mg/kg in rats accounts only for 0.5% of the dose, while the cumulative recovery from the bile at 10 h after 2.5 mg/kg i.v. administration in rats accounts for 5.5% of the dose.
Lack of in vitro and in vivo Selection of Bacterial Resistance by Roxithromycin
Authors: Drago Lorenzo , Fassina Maria Cristina , De Vecchi Elena , Mombelli Barbara , Lombardi Alessandra , Gismondo Maria Rita
Published: April 2003

The in vitro and in vivo selective pressure exerted by roxithromycin on Lancefield group A β-haemolytic streptococci (GABHS) was investigated. In vitro antimicrobial activity on fifty GABHS strains was determined by the microdilution method and by boundary concentration (BC) determination. Insorgence of resistance was evaluated by redetermining MIC and BC after exposure to 16 × MIC roxithromycin concentration. In vivo insorgence of resistance was evaluated by MIC and BC determinations on the GABHS strain recovered from infected mice peritoneum, after treatment with 20 mg/kg roxithromycin. The roxithromycin serum kinetics was established in healthy and infected mice. Neither significant changes in GABHS MIC or BC after in vitro or in vivo exposure to roxithromycin nor a difference in roxithromycin serum levels between healthy and infected mice were detected, suggesting that the roxithromycin selection of resistance in GABHS is low.
Postantibiotic Effect of a Combination of Antimicrobial Agents on Pseudomonas aeruginosa
Authors: Sood Poonam , Mandal Anandita , Mishra Bibhabati
Published: April 2003

Treatment of severe Pseudomonas infections often calls for multidrug therapy. Combinations of aminoglycosides, beta-lactams and/or quinolones are generally administered, the effect of which may be additive, synergistic or indifferent. The present in vitro study was designed to find out the exact outcome of the postantibiotic effect (PAE). The minimal inhibitory concentrations and the PAE of three antibiotics (amikacin, ceftazidime and ciprofloxacin) were determined both singly and in combination. Ceftazidime alone exhibited a negative PAE but a synergistic effect was observed for the combination of ceftazidime with amikacin. The combination of ceftazidime with ciprofloxacin and ciprofloxacin with amikacin however gave an indifferent PAE. This synergistic PAE of amikacin with ceftazidime has a significant effect on designing optimal dosage regimens.
Changes in Susceptibility of Pseudomonas aeruginosa to Gatifloxacin andCarbapenem in an in vitro Urinary BladderModel
Authors: Takahashi Satoshi , Hirose Takaoki , Sano Masato , Nishimura Masahiro , Matsukawa Masanori , Mikami Midori , Tsukamoto Taiji
Published: April 2003

To study the changes of bacterial susceptibility during exposure to antimicrobials, the respective minimal inhibitory concentrations (MICs) of 50 colonies from each of various bacterial test strains were determined in an experimental system using an in vitro urinary bladder model. The MICs of gatifloxacin and meropenem for Pseudomonas aeruginosa strains were not homogeneous before exposure to the drugs. The MICs of the strains examined reflected only that of their dominant population. When starting from 107CFU/ml, the bacterial count was determined serially during exposure to gatifloxacin or meropenem in therapeutic urinary concentrations. The MIC of the less susceptible population of each strain was changed serially to a higher one. The more susceptible strains were eradicated before the change of the MIC. The bacteria originally consisted of strains having heterogeneous susceptibility to drugs, in which major strains had susceptibility expressed by the MIC and minor ones had a higher or lower MIC. This heterogeneity may be responsible for the change of susceptibility in strains after exposure to the drugs.
Prospective Randomized Study of Antibiotic Prophylaxis for Nonlaparotomy Surgery in Benign Conditions
Authors: Hayashi Hiroaki , Yaginuma Yuji , Yamashita Tsuyoshi , Morizaki Atsushi , Ishiya Takayuki , Katou Yasuhito , Ishikawa Mutsuo
Published: April 2003

Background: Although postoperative infections continue to be a major problem in gynecologic surgery, there is still no consensus on the efficacy of antibiotic prophylaxis. Methods: This prospective randomized trial was conducted to investigate the prevention of major operating site infections after nonlaparotomy surgery, with treatment regimens as follows: the first group of patients received 2 g of intravenous cefotiam dihydrochloride (CTM) on the induction of anesthesia, while the second group received 100 mg of oral cefpodoxime proxetil (CPDX- PR) twice daily, from day 0 to day 2. Results: Nineteen of the 207 patients enrolled developed postoperative infections diagnosed by our simple criteria for postoperative infection. The frequency of febrile morbidity was not significantly less in patients who received CTM (9 cases; 8.6%) as compared with those in the CPDX-PR group (10 cases; 9.8%) (p = 0.56). Conclusion: The administration of oral CPDX-PR (100 mg, twice daily, for 3 days) appears to be a safe, cost-saving, convenient prophylaxis which reduces overall expense.
Systemic Infections with Candida sp. and Aspergillus sp. in Immunocompromised Patients with Hematological Malignancies: Current Serological and Molecular Diagnostic Methods
Authors: Buchheidt Dieter , Skladny Heyko , Baust Corinna , Hehlmann Rüdiger
Published: April 2003

Within recent years, novel serological and molecular methods have been developed to improve the early diagnosis of invasive fungal infections especially in patients with malignant hematological diseases being at highest risk of developing these life-threatening infections. Early diagnosis is essential for adequate therapeutic management, which, however, often remains difficult since the diagnostic tools clinically used either lack specificity or sensitivity, or both at worst. The clinical value, the advantages and remaining problems of recently developed, more sensitive and specific serological assays and molecular methods are reviewed.
In vitro Activity of Ceftazidime, Cefepime and Imipenem on 1,005 Pseudomonas aeruginosa Clinical Isolates either Susceptible or Resistant to Beta-Lactams
Authors: Bonfiglio Giovanni , Marchetti Federico
Published: April 2003

Background: Recently, new ‘fourth-generation’ cephalosporins, such as cefepime and cefpirome, were introduced into antibacterial chemotherapy. Methods: In order to explore whether these new cephalosporins offer real advantages against Pseudomonas aeruginosa, we matched the in vitro activity of cefepime with that of ceftazidime and imipenem as reference compounds. Results: Among the 1,005 clinical isolates tested, 86.6% were susceptible to ceftazidime, whereas 80.7 and 76.9% were susceptible to imipenem and cefepime, respectively. Furthermore, the activity of the three compounds against a significant number of clinical isolates of P. aeruginosa expressing different resistance mechanisms to β-lactam antibiotics was investigated. Among these isolates, 62.5% were still susceptible to ceftazidime, and 52.1 and 38.7% were inhibited by imipenem and cefepime, respectively. Conclusion: Ceftazidime and imipenem retained their activity against the majority of clinical P. aeruginosa isolates collected in Italy. Cefepime did not offer competitive advantages in terms of in vitro activity.
Potential Salvage Therapy for Accidental Intrathecal Vincristine Administration: A Preliminary Experimental Study
Authors: Özgen Ünsal , Soylu Hanifi , Önal S. Çaǧatay , Mizrak Bülent , Türköz Yusuf , Kutlu N. Onur , Koçak Ayhan , Özcan Cemal , Koltuksuz Uǧur , Erten S. Fuat , Akçin Übeyt
Published: April 2003

Background: Accidental intrathecal vincristine (VCR) administration results in severe neurotoxicity, usually fatal in outcome. No specific therapy for initrathecal VCR toxicity has been reported so far. In our recent report, complete in vitro degradation of VCR by hypochlorous acid (HOCl) was demonstrated. Methods: In this comparative study, we examined the in vivo effectivity of HOCl in the cerebrospinal fluid of 24 New Zealand rabbits following intracisternal VCR administration. Results: There were no significant clinical or histopathologic abnormalities in the control and HOCl groups; however, multiple necrotic foci on histopathological examination of brain sections in the VCR group were determined. There were significantly lower numbers of necrotic foci in brain sections of rabbits which received HOCl administration than those without therapy. Conclusion: Our results indicate that HOCl may reduce VCR neurotoxicity.
In vitro Comparative Dynamics of Modified-Release Clarithromycin and of Azithromycin
Authors: Scaglione F. , Demartini G. , Dugnani S. , Fraschini F.
Published: April 2003

Antibacterial kinetics of modified-release clarithromycin (CLA) and azithromycin (AZI) against respiratory tract pathogens were compared in relation to their pharmacokinetic profile. The study was carried out in three strains of Streptococcus pneumoniae, group A β-hemolytic Streptococcus pyogenes, Moraxella catarrhalis and Haemophilus influenzae, respectively, exposed to concentration gradients of CLA and AZI simulating human serum pharmacokinetics after administration of 500 mg p.o. in a single dose. Bactericidal kinetics were assessed by counting the number of survivors before each change in concentration over a period of 36 h. The minimal inhibitory concentrations (MICs) of CLA and AZI were evaluated at time 0 and after 36 h of exposure to antibiotics in the surviving organisms. The results showed that CLA and AZI, in the experimental conditions adopted, had different antibacterial kinetics. Moreover, the addition of the 14-OH metabolite of CLA at the same concentrations reached in human serum exerted a bactericidal effect against two strains of H. influenzae resistant to CLA and AZI. An increase in MICs was observed against S. pyogenes and H. influenzae, with higher values for AZI.
Safety and Efficacy of Cefpirome in Comparison with Ceftazidime in Chinese Patients with Sepsis due to Bacterial Infections
Authors: Fang Chi-Tai , Chen Yee-Chun , Lin Seng-Fong , Shau Wen-Yi , Liu Chieh-Ju , Sheng Wang-Huei , Wang Jen-Tay , Chang Shan-Chwen
Published: April 2003

Background: The safety and efficacy of cefpirome (CPM), a fourth-generation cephalosporin, has not yet been studied in an Asian population. Methods: Sixty-nine adult Chinese patients with sepsis due to bacterial infections were enrolled in the study and randomly assigned to receive CPM (2 g i.v. every 12 h) or ceftazidime (2 g i.v. every 8 h). Results: Both groups were comparable in terms of demographic, clinical and microbiological features. The causative pathogen was Escherichia coli or Klebsiella pneumoniae in the majority of microbiologically documented cases. The rates of clinical response (94 vs. 94%) and bacteriological response (65 vs. 68%) were similar in both groups. Similar adverse events, including rashes, gastrointestinal upset and asymptomatic elevation of hepatic enzymes, occurred in a minority of patients in both groups. All events were self-limited after discontinuation of the drugs. Conclusion: CPM is as safe and effective as ceftazidime in the treatment of sepsis due to bacterial infections in Chinese patients.
A Randomized Prospective Study of Oral versus Intravenous Antibiotic Prophylaxis against Postoperative Infection after Sagittal Split Ramus Osteotomy of the Mandible
Authors: Yoda Tetsuya , Sakai Eiki , Harada Kiyoshi , Mori Masaji , Sakamoto Ichiro , Enomoto Shoji
Published: April 2003

Background: We investigated whether oral levofloxacin was as effective as intravenous cefazolin sodium for preventing postoperative infections in patients undergoing sagittal split ramus osteotomy of the mandible. Methods: Forty-four patients were randomized to treatment with levofloxacin or cefazolin sodium. Levofloxacin (100 mg t.d.s.) was administered orally, and cefazolin sodium (1 g b.i.d.) by intravenous infusion. Both drugs were given until 5 days postoperatively. The concentrations of levofloxacin in the mandibular bone marrow and serum were measured. Results: The mean levofloxacin concentration 4 h and 53.7 min after administration was 1.086 μg/ml in serum and 1.328 μg/ml in the mandibular bone marrow. The efficacy rate of levofloxacin was 95% and that of cefazolin sodium was 85.7%, with no significant difference between the two drugs (p = 0.322). Conclusion: Oral administration of levofloxacin is a simple, cost-effective and safe alternative to intravenous antibiotic prophylaxis after mandibular surgery.
Tunicamycin Treatment Reduces Intracellular Glutathione Levels: Effect on the Metastatic Potential of the Rhabdomyosarcoma Cell Line S4MH
Authors: Calle Yolanda , Palomares Teodoro , Castro Begoña , del Olmo Maite , Bilbao Pedro , Alonso-Varona Ana
Published: April 2003

Highly metastatic cells are known to overexpress certain Asn-linked oligosaccharides in the plasmatic membrane. Another phenotypic characteristic of malignant cells consists in the expression of high levels of intracellular glutathione (GSH). The aim of the present work was to demonstrate that the inhibition of N-glycosylation induces changes in intracellular GSH levels, and in turn participates in the inhibition of the metastatic potential of tumor cells by tunicamycin treatment. Firstly, we demonstrated that in comparison to the poorly metastatic cell line F21, the highly metastatic cells S4MH express a higher number of Asn-linked β1–6 branched oligosaccharides and sialic acid (SA) and/or chitobiose oligosaccharides in glycoproteins involved in the regulation of the adhesion efficiency of tumor cells on endothelial cells and extracellular matrix. Our results showed that the decrease in S4MH cell adhesion efficiency on endothelial cells and extracellular matrix after the inhibition of N-glycan processing by tunicamycin treatment was caused by: (1) inhibition of the expression of N-glycan structures recognized by endothelial endogenous lectins, including β1–6 branched oligosaccharides and SA and/or chitobiose oligosaccharides, and (2) redistribution of cell surface glycoproteins with β1–6 branched oligosaccharides and/or SA and/or chitobiose oligosaccharides in their structures, caused by the depletion of intracellular GSH levels. The latter condition prevents the organization of these glycoproteins in the plasmatic membrane of S4MH cells necessary for anchoring to the substratum.
Intestinal Obstruction, ProgressiveWeight Loss, and Recurrent Feverin Two Patients with Mesenteric Lesions
Authors: Hoffmann Jörg C. , Lamberts Regina , Huppert Peter , Kaiserling Edwin , Gregor Michael
Published: April 2003

We describe 2 patients who presented with fever and incomplete intestinal obstruction. Previously, both patients had had laparotomies showing unresectable lesions in the root of the mesentery which were histologically diagnosed as sclerosing mesenteritis in the first and mesenteric fibromatosis in the second patient. In spite of aggressive immunosuppressive therapy the first patient deteriorated with high-grade fever and progressive weight loss. Similar symptoms occurred in the second patient. Computed tomographic scanning revealed necrotic lesions in both patients which histologically were found to be an angiocentric T-cell lymphoma in the first and a superinfected necrotizing fibroma in the second patient. It is therefore clinically and radiologically impossible to distinguish between the different causes of mesenteric lesions. Reoperation for further biopsies needs to be considered if such patients do not respond to medical treatment.
Analysis of Gastroduodenitis and Oesophagitis in Relation to Dyspeptic/Reflux Symptoms
Authors: Villani L. , Trespi E. , Fiocca R. , Broglia F. , Colla C. , Luinetti O. , Tinelli C. , Solcia E.
Published: April 2003

Background/Aims: The pathogenesis of dyspeptic/reflux symptoms and the clinico-pathologic profile of affected patients are still poorly understood. To improve our knowledge in this field we carried out a systematic, comparative analysis of symptom profiles and histopathologic patterns of oesophagogastroduodenal mucosa in a series of 221 subjects, 140 with and 81 without endoscopic evidence of hiatal hernia. Of these, 190 showed reflux and/or dyspeptic symptoms. Methods: Before endoscopy, all the subjects were questioned about the presence and severity of 12 individual symptoms. Biopsies were taken from the distal oesophagus, cardia, corpus, angulus, antrum and duodenal bulb, and were scored in accordance with the Sydney system. Results: Patient groups with a distinct clinico-pathologic profile were better identified when symptoms of adequate severity were compared with histopathologic parameters. A correlation between gastroesophageal reflux disease (GORD) symptoms and histologic signs of oesophagitis was mostly restricted to patients endoscopically positive for oesophagitis. Retroxiphoid pyrosis correlated with cardial gastritis but not with oesophagitis, either endoscopic or histologic, while ulcer-like epigastric pain correlated with active duodenitis and distal gastritis. No definite histopathologic background was detected in patients with putative dysmotility-like symptoms, endoscopy-negative GORD and low score or mixed symptoms. Conclusion: A contribution of Helicobacter pylori gastroduodenitis to the pathogenesis of some dyspeptic symptoms seems likely. However, the identification of specific histologic changes causing individual symptoms remains rather elusive, with the exception of active antroduodenitis in patients with ulcer-like pain and of active proximal gastritis in patients with severe retroxiphoid pyrosis.
Intestinal Absorption and Enterohepatic Circulation of Folic Acid: Effect of Ethanol
Authors: Fernández O. , Carreras O. , Murillo M.L.
Published: April 2003

This study sought to determine the intestinal in vivo absorption of folic acid by the whole intestine, and the appearance of this compound in bile in control and ethanol-fed rats. Intestinal folic acid absorption in rats with the bile duct cannulated decreased in ethanol-fed rats with respect to control rats. This difference was significant at 1 and 2.5 µM concentrations of folic acid. This result is in contrast with previous work in our laboratory on rats with intact bile ducts, where ethanol-fed rats had an increase in folic acid absorption. The results obtained in the present work suggest an impaired enterohepatic recycling of folic acid in ethanol-fed rats.
Anastomotic Blood-Flow Reduction in Rat Small Intestine with Chronic Radiation Damage
Authors: Jahnson S. , Holtz A. , Gerdin B.
Published: April 2003

Background/Aims: Anastomoses in previously irradiated intestine are prone to leakage, possibly due to an impeded blood supply. Whether or not chronic radiation damage actually predisposes to a disturbed blood flow in the vicinity of anastomoses was investigated in the rat small bowel. Method: A 2-cm segment of rat ileum was irradiated with a single dose (21 Gy). After 20 weeks an anastomosis was created in the irradiated segment and in the corresponding segment of controls. Another 4 days later local blood flow was studied with the 14C-iodoantipyrine autoradiography technique in 16 sectors around the circumference both in the anastomotic segment and in a segment 4 mm apart. Results: In the anastomotic segment, the average blood flow was reduced in irradiated compared with non-irradiated animals in the mucosal layer (p = 0.034), but not in the muscular layer (p = 0.08). In the mesenteric quadrant blood flow was reduced in irradiated compared with non-irradiated animals, both in the mucosal layer (p = 0.012) and in the muscular layer (p = 0.05). More irradiated than non-irradiated animals showed a blood-flow reduction to 15% or more in 13–16 sectors both in the mucosal (p = 0.015) and the muscular layer (p = 0.04). Conclusions: The results favor the hypothesis that anastomoses in previously irradiated intestine are vascularly compromized and thereby have an increased risk of leakage.
Colon Epithelium Can Be Transiently Transfected with Liposomes, Calcium Phosphate Precipitation and DEAE Dextran in vivo
Authors: Liptay Susanne , Weidenbach Hans , Adler Guido , Schmid Roland M.
Published: April 2003

Background: The introduction of recombinant DNA into cells is the initial step toward the development of gene therapy. It has been shown that cationic liposomes are useful vehicles to introduce DNA into colon epithelial cells in vivo. Methods: In the present study we compared the efficacy of different nonviral transfection methods into the colon wall. In anesthetized rats, a double balloon catheter was advanced into the colon and a chloramphenicol acetyltransferase (CAT) reporter plasmid complexed to liposomes, mixed with DEAE dextran, or precipitated with calcium phosphate was instilled. Following 2 days CAT activity was determined in the transfected colon segments. Results: DEAE dextran and liposomes were more effective than calcium phosphate, whereas naked DNA was not taken up by the colon epithelial cells. Reporter gene expression was dose-dependent. Expressing cell types did not differ utilizing the various transfection methods as judged by X-gal staining of colon sections after transfection with a LacZ reporter plasmid. Conclusion: These data indicate that in addition to liposomes, plasmid DNA mixed with DEAE dextran can be taken up by colon epithelial cells. This transfection techniques may prove useful in the development of gene therapy approaches for colon disease.
Growth and Recurrence of Colorectal Polyps: A Double-Blind 3-Year Intervention with Calcium and Antioxidants
Authors: Hofstad Bjorn , Almendingen Kari , Vatn Morten , Andersen Solveig Norheim , Owen Robert W. , Larsen Stig , Osnes Magne
Published: April 2003

Background: Dietary calcium and antioxidants have been suggested as protective agents against colorectal cancer. This has been supported by animal experimental studies, case control and cohort studies. Materials and Methods: In a prospective intervention study of colorectal adenomas, and intermediary stage in colorectal carcinogenesis, 116 polyp-bearing patients received a placebo-controlled daily mixture of β-carotene 15 mg, vitamin C 150 mg, vitamin E 75 mg, selenium 101 µg, and calcium (1.6 g daily) as carbonate for a period of 3 years with annual colonoscopic follow-up to test if the mixture was able to reduce polyp growth or recurrence. All polyps of <10 mm at enrolment or follow-up were left unresected until the end of the study. Results: 87–91% of the patients attended the annual endoscopic follow-up investigations, and 19% of the patients dropped out of the medical intervention. The rest consumed 85% of the total amount of tablets over the 3 years. The fecal calcium concentration was 2.3–2.7 times higher in patients taking active medication compared to the placebo group. Diet registration showed that, when adding the intake of antioxidants and calcium from diet and intervention, there was a significant difference between the intake of these substances in the active and the placebo group. No difference was detected in the growth of adenomas between the active and the placebo group from year to year and for the total study period. Moreover, there was no effect on polyps of <5 or 5–9 mm, or on polyps in the different colonic segments analyzed separately. A reduced growth of adenomas was found in patients <60 years of age taking active medication (n = 8) compared to those taking placebo (n = 6; mean difference 2.3 mm; 95% CI 0.26–4.36). There was a significantly lower number of patients free of new adenomas in the placebo group compared to those taking active medication as tested by logistic regression and Kaplan-Meier analysis (log-rank test p value 0.035). Subgroup analysis showed that only the group of patients with no family history of colorectal cancer, those with only one adenoma at inclusion, and those <65 years benefitted from the intervention medication. Conclusion: The study did not find an overall effect on polyp growth. Our data, however, may support a protective role of calcium and antioxidants on new adenoma formation.
Chlamydia trachomatis Infection: Is It Relevant in Irritable Bowel Syndrome?
Authors: Francis Carol , Prior Alison , Whorwell P.J. , Morris Julie
Published: April 2003

Background: Irritable bowel syndrome can present with gynaecological symptoms similar to those of chronic pelvic inflammatory disease, which is commonly caused by Chlamydia trachomatis. Infection with this organism might therefore lead to diagnostic and management difficulties in patients, not only as a result of symptom overlap between the two disorders but also because chlamydial infection might exacerbate the symptoms of irritable bowel syndrome. This study was designed to investigate any possible link between chlamydial infection and irritable bowel syndrome. Patients/Methods:  The prevalence of antibodies to C. trachomatis and abdominal symptomatology was assessed in a group of 100 female patients with irritable bowel syndrome and 100 matched female controls. Results: 25% of patients and 17% of controls were found to have evidence of previous chlamydial infection. This difference was not statistically significant. Within the patient group, no association was found between chlamydial infection and any particular pattern of symptomatology. Conclusions: The results of this study indicate that occult chlamydial infection is not a major problem in irritable bowel syndrome and that routine investigation for this organism is unnecessary. They also provide some reassurance that pelvic inflammatory disease and all its potentially serious consequences is not being significantly overlooked in gastroenterological practice.
Gastric Carcinoid with Histamine Production, Histamine Transporter and Expression of Somatostatin Receptors
Authors: Kölby Lars , Wängberg Bo , Ahlman Håkan , Jansson Svante , Forssell-Aronsson Eva , Erickson Jeffrey D. , Nilsson Ola
Published: April 2003

A case of sporadic, histamine-producing gastric carcinoid with liver metastases is reported. The patient was treated with somatostatin analogue (octreotide) combined with cortisone and blockade of histamine receptors prior to surgery, which included subtotal gastrectomy, excision of lymph node metastases and superficial liver metastases. Residual liver metastases were injected with ethanol. These interventions markedly reduced the urinary excretion of the main histamine metabolite (MeImAA). Eighteen months later combined immuno- and chemotherapy was initiated due to tumour progression and recurrent hormonal symptoms with good clinical results over 12 months. Scintigraphy, using 111In-DTPA-D-Phe1-octreotide, visualized somatostatin receptors (sstr) in primary tumour, lymph node metastases and liver metastases. The tissue/blood 111In concentration ratios of tumour biopsies were very high. Northern analyses confirmed expression of all subtypes of sstr1–5. Immunocytochemically, tumour cells were strongly positive for chromogranin A, histamine and vesicular monoamine transporter (VMAT) 2 (histamine transporter), but negative for VMAT 1, suggesting an origin from gastric enterochromaffin-like cells. In primary tumour cell cultures, histamine, 5-HTP and 5-HIAA, but not 5-HT, could be detected in conditioned culture medium, indicating a defective decarboxylation of the tryptamine precursor. This rare case of histamine-producing gastric carcinoid demonstrates that excellent symptom relief can be achieved despite disseminated disease, if active, multimodal treatment strategy is instituted. The presence of high numbers of sstr in tumour tissue also raises the possibility of receptor-guided radiotherapy.
Pancreatitis-Associated Protein Is Upregulated in Mouse Pancreas during Acute Pancreatitis
Authors: Bödeker Hans , Fiedler Fritz , Keim Volker , Dagorn Jean-Charles , Iovanna Juan Lucio
Published: April 2003

Pancreatitis-associated protein I (PAP I) is a pancreatic secretory protein strongly expressed during acute pancreatitis in the rat and human. We hypothesized that its expression was part of a general and coordinated response of the organ against aggression. An opposite pattern of PAP I mRNA expression has recently been described in the mouse. The murine PAP I mRNA was described to be highly expressed in normal pancreas and down-regulated during pancreatitis. The important implications of these unexpected findings led us to investigate the expression of murine PAP I in cerulein-induced pancreatitis. Northern blot analysis demonstrated a very low level of PAP I mRNA in the healthy mouse pancreas and strong overexpression during acute pancreatitis. Western blot analysis confirmed that changes in pancreatic PAP I levels were parallel to those of the mRNA and the protein was localized by immunohistochemistry to the acinar cells. It was concluded that, during the course of acute pancreatitis, the pattern of PAP I expression in the mouse pancreas was comparable to that already observed in the rat and human. Although we have no explanation for the discrepancy between our results and those recently reported, the expression pattern of PAP I in the mouse exocrine pancreas described in the present study suggests that the pancreatic response to aggression might be conserved in mammals.
Ischemia-Reperfusion-Induced Delay in Intestinal Transit
Authors: Alican İnci , Yegen Cumhur , Olcay Ayhan , Kurtel Hızır , Yegen Berrak Ç.
Published: April 2003

Background/Aims: To evaluate the involvement of ET-1 in ischemia-reperfusion (I/R) injury. Methods: Superior artery occlusion was performed in Wistar albino rats for 30 min followed by 2-hour (early reperfusion; ER) or 24-hour (late reperfusion; LR) reperfusion periods. Results: Intestinal transit was found to be reduced in the ER and LR groups (19.0 ± 2.5%; p < 0.001 and 72.7 ± 6.0%; p < 0.05, respectively) compared to the control group (85.8 ± 2.5%), while treatment with the ET receptor antagonist bosentan (BOS; 10 mg/kg i.v.) abolished this delay in LR. Myeloperoxidase activity showed a significant increase in ER (7.07 ± 85.70 U/g; p < 0.001) compared to control (281.16 ± 43.23 U/g), but BOS had no effect on this increase. The protein oxidation level was found to be higher in LR (5.92 ± 0.77 nmol/mg protein; p < 0.05) compared to the control (3.77 ± 0.45 nmol/mg protein), and was reversed by BOS treatment. Conclusion: The results of the present study imply that I/R delays intestinal transit involving an endothelin-dependent mechanism.
Recent Discoveries in Cancer Genetics of Exocrine Pancreatic Neoplasia
Authors: Hahn Stephan A. , Schmiegel Wolff H.
Published: April 2003

Within the past 4 years major advances in our understanding of pancreatic carcinogenesis have been made. The discovery of a high frequency of mutations in the tumor suppressor genes p16 and p53 together with an extraordinary high rate of K-ras mutations have shed light on how the disturbance of cell cycle control is a major hallmark in this tumor type. Furthermore, another very recently identified tumor suppressor gene, DPC4 (deleted in pancreatic carcinoma, locus 4), revealed that the TGFβ-Smad signalling pathway is also likely to contribute to the development of this tumor type. It is now hoped that our improved knowledge of the molecular profile of pancreatic carcinoma will also translate into better diagnostic and therapeutic options to deal with this dismal disease.
Treatment of Hepatocellular Carcinoma
Authors: Tang Zhao-You
Published: April 2003

Treatment of hepatocellular carcinoma (HCC) remains a critical issue particularly in the endemic areas. This paper summarizes the literature in the recent 4 years and the author’s data. Substantial progress has been found in the treatment of HCC during the recent decades, which was mainly a result of advances in medical imaging, aggressive surgical approach, regional cancer therapies and multidisciplinary approach. Surgical approaches that resulted in significant prolonged survival included: resection (particularly small HCC resection), re-resection for subclinical recurrence, cytoreduction and sequential resection for initially unresectable HCC, and liver transplantation for small HCC. In nonsurgery, regional cancer therapy has been a new trend, which includes transcatheter arterial chemoembolization, percutaneous ethanol injection for small HCC, and others. As a result of multimodality combination treatment and changing concepts in surgical oncology, the role of surgery in the treatment of HCC has become bigger. However, the inadequacy of regional cancer therapies, its multicentric origin and tumor invasiveness remain major targets to be studied for a curative treatment.
Decreased Helicobacter pylori- Specific Gastric Secretory IgA Antibodies in Infected Patients
Authors: Birkholz S. , Schneider T. , Knipp U. , Stallmach A. , Zeitz M.
Published: April 2003

Despite an increase in local Helicobacter pylori-specific IgA production in H. pylori infection, the bacterium is able to persist over decades. We focused on IgA and secretory IgA (sIgA) in gastric juice because sIgA is more relevant in local protection and more resistant to degradation than nonsecretory IgA. H. pylori-specific IgA and sIgA in gastric juice, saliva, and serum of H. pylori-infected patients were compared. Samples from 28 H. pylori-positive and 16 negative patients were tested by means of immunoblotting for the presence of H. pylori-specific IgA and sIgA. In gastric juice the majority of H. pylori-specific IgA was not of the secretory type, whereas total IgA was bound mainly to the secretory component as shown by immunoblot and slot blot. In contrast H. pylori-specific IgA antibodies in saliva of infected patients were of the secretory type as shown by immunoblot. The presence of specific, nonsecretory IgA may be a consequence of the damaged mucosal epithelium at the site of H. pylori infection allowing IgA to bypass the secretory transport system. Considering the resistance of secretory IgA against hydrolysis and proteolysis, these data suggest that the predominantly nonsecretory IgA specific for H. pylori may lead to a decreased protection against H. pylori.
Sodium Chloride Transport of Normal and Dietary Enlarged Rat Cecum in vitro
Authors: Schreiner Josefine , Weber Matthias , Loeschke Klaus
Published: April 2003

Sodium chloride transport across isolated cecum mucosa was investigated in normal rats and rats with adaptive cecum growth induced by dietary polyethylene glycol (PEG). The normal cecum absorbed Cl in excess of Na with a small short-circuit current (ISC). Dietary adaptation led to large equivalent increments of Na and Cl net absorption without adequate ISC change. Inhibitor studies (mucosal amiloride 10–3 and 10–4 M; mucosal 4,4-diisothiocyanatostilbene-2,2-disulfonic acid 5 × 10–5 M; serosal furosemide 10–3 M; serosal ouabain 10–3 M) suggested that normal cecal NaCl absorption involves electroneutral Na/H and Cl/HCO3 exchange at the apical and Na-K-ATPase-mediated exit across the basolateral cell membrane. Dietary adaptation stimulates the loosely coupled antiports and possibly activates a small serosally located NaCl cotransport. Comparative histology showed flattening of all tissue layers and widening of crypts in PEG animals. Crypt widening may facilitate ion access to underutilized transport sites and, at least in part, explain the increased absorption of the enlarged cecum.
Differential Distribution of Serotonin and Tryptophan Hydroxylase in the Human Gastrointestinal Tract
Authors: Meyer Thomas , Brinck Ulrich
Published: April 2003

The distribution of tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of serotonin, was investigated immunohistochemically in various organs of the gastrointestinal tract and compared with that of neuroendocrine markers. While immunoreactivity for serotonin and chromogranin A was restricted to enterochromaffin cells, positive staining for tryptophan hydroxylase was detected in normal enterocytes lining the epithelium of the small intestine. Tryptophan hydroxylase was localized in the supranuclear cytoplasm of absorptive cells, and was absent from the terminal web. The enterocytes of the exfoliation zone at the tips of the villi demonstrated a strong immunoreactivity similar to those at the slope of the villi. Mucus-containing Goblet cells, Paneth cells and stromal cells of the lamina propria remained unlabelled. The duodenal glands of Brunner revealed only sporadically a weak immunostaining for tryptophan hydroxylase. The monooxygenase was also detected in numerous secretory tubules of the pyloric mucosa, where the proportion of positive cells decreased progressively from the crypts towards the upper parts of the gastric glands. No significant immunoreactivity was demonstrated in colon, adrenal cortex, liver, pancreas, and mesenteric lymph nodes. The demonstration of tryptophan hydroxylase in normal enterocytes suggested that epithelial cells of the small intestine are able to synthesize 5-hydroxytryptophan.
The Safety of Hot Biopsy Forceps in the Removal of Small Colonic Polyps
Authors: Mann N.S. , Mann S.K. , Alam I.
Published: April 2003

Nine hundred and seven polyps (mean size 3.7 mm; range 2–8) from 460 patients (mean age 67 years; range 34–94) were removed with monopolar electrocoagulation forceps (‘hot biopsy forceps’). Sixty-three percent of the polyps were adenomatous and 36% were hyperplastic. In this series there were 3 cancers and 1 neurofibroma. About 42% of the polyps were in the sigmoid-rectum region; the rest were evenly distributed in the remaining part of the colon. There were no complications. Specifically there were no cases of perforation or massive bleeding after removal of these polyps. Within the guidelines mentioned, hot biopsy removal of small colonic polyps is safe.