bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro Activity of Levofloxacin against Gram-Positive Bacteria
Authors: Montanari Maria Pia , Mingoia Marina , Marchetti Federico , Varaldo Pietro Emanuele
Published: April 2003

The in vitro activity of levofloxacin was investigated against 256 clinical strains of four gram-positive genera (Staphylococcus, Streptococcus, Enterococcus, and Listeria). Ofloxacin and ciprofloxacin were used as comparators. Uniform susceptibility to levofloxacin was recorded among methicillin-susceptible staphylococci, streptococci other than Streptococcus agalactiae, regardless of their being susceptible, intermediate, or resistant to penicillin (S. pneumoniae) or erythromycin (S. pyogenes and S. pneumoniae), in enterococci other than Enterococcus faecalis and E. faecium, and in Listeria monocytogenes isolates. Moreover, 1 of 22 S. agalactiae isolates and 1 of 19 E. faecium isolates was resistant, and 2 of 19 were intermediate. Resistances to levofloxacin with MIC90s in the resistance range were only observed in methicillin-resistant staphylococci and E. faecalis isolates. In any case, the MICs of ofloxacin and ciprofloxacin were usually 2–4 times higher than those of levofloxacin. In time-kill assays using three test strains (a methicillin-susceptible Staphylococcus aureus isolate, a penicillin-susceptible Streptococcus pneumoniae isolate, and an E. faecalis isolate), the bactericidal activity of levofloxacin was greater than that of ciprofloxacin.
Overview of SPA-S-843 in vitro Activity against Filamentous Fungi
Authors: Rimaroli Claudio , Bruzzese Tiberio
Published: April 2003

In this study, we investigated the in vitro antifungal activity of a new water-soluble partricin A derivative, N-dimethylaminoacetyl-partricin A 2-dimethylaminoethylamide diascorbate, coded SPA-843, currently developed by Società Prodotti Antibiotici. The activity of SPA-S-843 was compared to that of amphotericin B against 13 strains of Aspergillus spp., 4 strains of Mucor sp., 4 strains of Rhizopus oryzae, 2 strains Paecilomyces variotii, 5 strains of Penicillium spp., 1 strain of Sporothrix schenkii, 7 strains of Trichophyton spp. and 2 strains of Microsporum spp.; the minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) were measured for all the organisms. The in vitro susceptibility testing method employed was an adaptation of the macrodilution reference method for yeasts as described in the National Committee for Clinical Laboratory Standards document M27-A. The in vitro inhibitory activities of SPA-S-843 and amphotericin B against the fungi were evaluated in RPMI-1640 supplemented with L-glutamine and buffered with morpholinepropanesulfonic acid, while the in vitro fungicidal activities were determined by subculturing 0.1 ml from all tubes with no visible growth onto drug-free Sabouraud dextrose agar plates. Comparison with amphotericin B showed that the in vitro inhibitory activity of SPA-S-843 against Aspergillus spp. was better than that of amphotericin B and similar against R. oryzae, P. variotii, Penicillium spp. and S. schenkii. Amphotericin B presented geometric means (GM) of the MICs lower than those of SPA-S-843 against Mucor sp., Microsporum spp. and Trichophyton spp. SPA-S-843 was most fungicidal against Mucor sp. and P. variotii; SPA-S-843 and amphotericin B showed the same fungicidal activity against Aspergillus spp. (GM of the MFCs 12.53 μg/ml), Penicillium spp. (about 12 μg/ml) and S. schenkii (MFC 19.2 μg/ml). Amphotericin B presented GM of the MFC values lower than those of SPA-S-843 against R. oryzae, Microsporum spp. and Trichophyton spp.
Adjuvant Effect of Clarithromycin on Chemotherapy for Murine Lung Cancer
Authors: Hamada Kaoru , Mikasa Keiichi , Yunou Yoshihisa , Kurioka Takaaki , Majima Toshimasa , Narita Nobuhiro , Kita Eiji
Published: April 2003

Clarithromycin (CAM) increased the median survival of patients with unresectable non-small-cell lung cancer who had received chemotherapy and/or radiotherapy [Chemotherapy 1997;43:288–296]. The present study was performed to ascertain whether CAM alone exhibits an antitumor effect against Lewis lung carcinoma (LLC) and to analyze the nature of its adjuvant effect on LLC-inoculated C57BL/6 mice. CAM at 10 mg/kg/day retarded the growth of subcutaneously inoculated LLC cells; consequently, the mean survival time of mice with LLC increased. This treatment was also effective in reducing the number of tumor nodules in the lung after intravenous inoculation with LLC cells. When tumor-bearing mice received an intravenous injection of vindesine sulfate (7 mg/kg) and cisplatin (6 mg/kg) 7 days after tumor inoculation, the chemotherapeutic effect was significantly enhanced by CAM treatment when it started 7 days after chemotherapy, but not when it started the day after chemotherapy. The delayed initiation of CAM treatment resulted in the enhancement of natural killer cell activity and CD8+ T cell cytotoxicity and increased the number of interferon-γ-producing T cells and interleukin-4-producing T cells. These findings indicate that CAM can exhibit an antitumor effect by itself and also induce the well-balanced expansion of helper T cell subsets in tumor-bearing mice recovering from the immunosuppression caused by chemotherapy. CAM may therefore be a promising adjuvant drug in anticancer chemotherapy, and treatment with this macrolide should be initiated at some interval after basic cancer therapy.
Flucytosine: Correlation between Toxicity and Pharmacokinetic Parameters
Authors: Vermes Andras , van der Sijs Heleen , Guchelaar Henk-Jan
Published: April 2003

Flucytosine (5-fluorocytosine, 5-FC) is a systemic antimycotic drug the major toxicities of which are bone marrow depression and hepatotoxicity. The purpose of this observational and retrospective study was to assess a possible relationship between toxicity and 5-FC pharmacokinetics within a group of 53 intensive care unit patients. The presented results reveal that thrombocytopenia is associated with a decreased 5-FC clearance and that the thrombocyte nadir is linearly related to the 5-FC clearance. Furthermore, patients experiencing 5-FC levels exceeding 100 mg 5-FC/l were found to be at a higher risk of developing thrombocytopenia and hepatotoxicity as compared to those not exceeding this level.
In vitro Effects of Meropenem and Imipenem/Cilastatin on Some Functions of Human Natural Effector Cells
Authors: Cornacchione P. , Scaringi L. , Capodicasa E. , Fettucciari K. , Rosati E. , Sabatini R. , Benedetti C. , Marconi P. , Rossi R. , Del Favero A.
Published: April 2003

Meropenem, a new carbapenem antibiotic, was assessed to evaluate its effects on some functional parameters of human polymorphonuclear (PMN) and natural killer (NK) cells in comparison with imipenem/cilastatin. Both drugs significantly inhibited PMN phagocytosis and chemotaxis at concentrations of 2,000 and 4,000 μg/ml. They affected PMN microbicidal activity, evaluated against Candida albicans, only at 4,000 μg/ml. A study of the effects of both drugs on peripheral NK populations and the human NK line (NK-92) showed that even at 4,000 μg/ml there was no effect on antitumor activity. These data indicate that meropenem can reduce some PMN antimicrobial functions only at very high concentrations like imipenem/cilastatin, whereas no concentration influenced NK activity.
Antimicrobial Resistance Patterns in Respiratory Pathogens Isolated in an Italian University Hospital during a Period of Eight Years: A Statistical Analysis
Authors: Dos Santos C. , Capelo A. , Cimbro M. , Ferrara A.
Published: April 2003

The antimicrobial resistance patterns of respiratory pathogens isolated during an 8-year period (1990–1997) in an Italian hospital from patients with bronchopulmonary infections were investigated. A global variation in the resistance of Staphylococcus aureus to all relevant antibiotics was observed during the years 1990–1997. With the exception of penicillin and amoxicillin, to which Staphylococci were always resistant, and vancomycin, to which they were always susceptible, in the first period (1990–1992) the percentage of resistance to β-lactams, aminoglycosides, macrolides, fluoroquinolones and cotrimoxazole was about 15%, while in the last period (1993–1997) it was about 35%. No global variation in resistance to the antimicrobials examined during the study period was observed for gram-negative bacteria. The percentages of resistance to the more recent β-lactams, aminoglycosides and fluoroquinolones were generally less than 10% for the KES group, less than 20% for Pseudomonas aeruginosa, and less than 30% for other Pseudomonas species. A high percentage of resistance was observed for the KES group to amoxicillin + clavulanic acid (60%) and to cefoxitin (48%).
Interaction of Cefotetan and the Metallo-β-Lactamases Produced in Aeromonas spp. and in vitro Activity
Authors: Quiroga M.I. , Franceschini N. , Rossolini G.M. , Gutkind G. , Bonfiglio G. , Franchino L. , Amicosante G.
Published: April 2003

Aeromonas spp. are increasingly being recognized as human pathogens. The presence of metallo-β-lactamases in these organisms represents a potential problem in antimicrobial therapy. Mechanism-based inactivators of β-lactamases are used to overcome the resistance of clinical pathogens to β-lactam antibiotics, but no clinical useful inhibitors of the metallo-β-lactamases are presently known. Studying the interaction between cefotetan and Aeromonas spp. producing metallo-β-lactamase activity, we observed that cefotetan behaved as a transient inactivator for both the crude extracts of Aeromonas strains and the purified enzymes from Aeromonas hydrophila AE036 and Aeromonas schubertii MNSA20. The direct hydrolysis of cefotetan showed that it was a poor substrate for both purified enzymes. In view of the minimum inhibitory concentrations, cefotetan shows to be a useful antimicrobial agent against Aeromonas spp.
In vitro Effects of Clarithromycin on Human Polymorphonuclear Leukocyte Functions
Authors: Kadir Tanju , İzzetin Fikret Vehbin , Çevikbaş Adile , Johansson Candan B. , Clark Philip
Published: April 2003

Background: It has been shown that antibacterial agents affect polymorphonuclear leukocytes (PMNs), which are active in the body’s first line of defense, in different ways. However, few studies have investigated the effects of tablet dosage forms as opposed to pure powder forms. There is a need to demonstrate the clinical relevance of previous results with commercially available products. Methods: We examined the effects of clarithromycin solutions, prepared separately from either pure powder or commercially available tablets (250 mg), on human PMNs. The in vitro effects of each solution, adjusted to therapeutic concentration (1 mg/l), on PMN adherence, chemotaxis, phagocytosis, candidacidal capacity and superoxide production were studied. Results: Solutions prepared from pure clarithromycin powder did not affect the adherence, phagocytosis or superoxide production of PMNs, but did inhibit (p < 0.05) chemotaxis and candidacidal capacity. By contrast, a decrease (p < 0.05) in all functions except phagocytosis was observed with solutions prepared from the tablet dosage form of clarithromycin. Conclusion: The results of this study suggest that the tablet dosage form of clarithromycin may have a more pronounced inhibitory effect on human PMN functions than solutions prepared from the pure powder form.
Exposure to Subtherapeutic Concentrations of Polyene Antifungals Suppresses the Adherence of Candida Species to Denture Acrylic
Authors: Egusa H. , Ellepola A.N.B. , Nikawa H. , Hamada T. , Samaranayake L.P.
Published: April 2003

Background: The adherence of Candida species to denture acrylic is the initial event leading to Candida-associated denture stomatitis, with Candida albicans being the main aetiological agent. However, the increased incidence of immunocompromised patients in the community has resulted in the emergence of a number of non-albicans Candida species as causative agents of this disease, which is commonly managed by topically delivered polyene antifungals. Hence, we investigated the effect of the exposure of denture acrylic surfaces to nystatin and amphotericin B on the subsequent adhesion of six different Candida species. Methods: Acrylic strips were exposed to subtherapeutic concentrations of the two polyenes for 30 min, and the adhesion of 4 isolates each of C. albicans, Candida glabrata, Candida guilliermondii, Candida krusei, Candida parapsilosis and Candida tropicalis was assessed using a previously described in vitro method with slight modifications. Results: Overall, the results indicated a 35.9% (p < 0.01) and 63.1% (p < 0.01) reduction, respectively, in yeast adhesion to denture acrylic following exposure to nystatin and amphotericin B, although this effect was not uniform for all the tested isolates. Thus, all C. glabrata, 3 C. guilliermondii and a single isolate each of C. krusei, C. parapsilosis and C. tropicalis were not significantly affected by nystatin exposure, and a single isolate each of C. glabrata and C. guilliermondii were not significantly affected by amphotericin B. Conclusions: The present data, the first on the effect of polyenes on a wide range of Candida species, indicate that the in vitro exposure of denture acrylic to subtherapeutic concentrations of nystatin and amphotericin B suppresses the adherence of pathogenic Candida species in general.
Comparative in vitro Activity of Older and Newer Fluoroquinolones against Respiratory Tract Pathogens
Authors: Esposito Silvano , Noviello Silvana , Ianniello Filomena
Published: April 2003

The aim of this study was to evaluate the antibacterial activity of older (ciprofloxacin and ofloxacin) and newer (moxifloxacin, grepafloxacin, sparfloxacin and levofloxacin) fluoroquinolones. Minimal inhibitory concentrations (MICs) were determined, according to the NCCLS guidelines, against the following respiratory tract pathogens: penicillin-susceptible and -resistant Streptococcus pneumoniae, β-lactamase-positive and βlactamase-negative Haemophilus influenzae and β-lactamase-positive Moraxella catarrhalis. In addition, we evaluated the minimal bactericidal concentrations of the same antibiotics against all the pneumococci and the haemophili. Finally, the activity of ciprofloxacin, ofloxacin, sparfloxacin and moxifloxacin against 15 pneumococci were investigated by time-kill analysis. All fluoroquinolones tested exhibited a similar, good activity against H. influenzae and M. catarrhalis. Against S. pneumoniae, irrespective of penicillin susceptibility, moxifloxacin, grepafloxacin, sparfloxacin and levofloxacin exhibited excellent activity, better than ciprofloxacin and ofloxacin. Time-kill analysis showed that 99.9% killing of all strains was obtained after 24 h with moxifloxacin at 2 × MIC, whereas other antimicrobials obtained similar results at 4 × MIC. Moxifloxacin is characterized by an improved activity against respiratory pathogens, including penicillin-resistant and -susceptible S. pneumoniae. Its activity is not influenced by β-lactamase production. These results suggest that moxifloxacin represents a promising alternative for treatment of respiratory tract infections.
Antibiotic Susceptibility of Serratia marcescens and Serratia liquefaciens
Authors: Traub Walter H.
Published: April 2003

Background: Over a period of 20 years, a total of 1,603 Serratia isolates were recovered from clinical specimens and examined for susceptibility to 29 antimicrobial drugs using the Bauer-Kirby agar disk diffusion test. Serratia marcescens was recovered most frequently (n = 1,409), followed by S. liquefaciens (n = 172); other Serratia species were scarce. During the 2-decade observation period there occurred 35 putative episodes/clusters of nosocomial cross-infection and 1 pseudo-outbreak due to S. marcescens, but none due to S. liquefaciens. Methods: The antimicrobial susceptibility data for S. marcescens and S. liquefaciens were subdivided into two observation periods: I = 1980–1993, and II = 1993–1999. The crude data (series A) obtained for S. marcescens were corrected in two ways: by the omission of repetitive patient isolates (series B) and the additional removal of outbreak isolates except for index case isolates (series C). Results and Conclusions: Comparison of data obtained in series IC and IIC disclosed an increase in the susceptibility of S. marcescens to ampicillin + sulbactam, cefotaxime, chloramphenicol, doxycycline, fosfomycin, gentamicin, piperacillin, piperacillin + tazobactam, timentin and tobramycin during observation period II. Conversely, there was a decrease in susceptibility to ciprofloxacin, nalidixic acid and trovafloxacin, and slightly diminished susceptibility to norfloxacin and ofloxacin during observation period II as compared with the previous period. The crude data obtained for S. liquefaciens required no correction, as there were only a few repeat isolates. There was an increase in susceptibility to ampicillin, ampicillin + sulbactam, cefuroxime, doxycycline, fosfomycin, nitrofurantoin and polymyxin B (clear inhibition zones). However, there was an inexplicable decrease in susceptibility to piperacillin + tazobactam. Cocarde growth around polymyxin B disks was noted with 55.8% of the S. marcescens isolates as compared with 6.8% of the S. liquefaciens isolates. Slime around fluoroquinolone inhibition zones was produced by 83.4% of the S. marcescens isolates. Slime production around carbapenem inhibition zones was noted with 52% of the S. liquefaciens isolates, but with only a single isolate of S. marcescens.
In vitro Susceptibility to Itraconazole, Clotrimazole, Ketoconazole and Terbinafine of 100 Isolates of Trichophyton rubrum
Authors: Fernández-Torres B. , Vázquez-Veiga H. , Llovo X. , Pereiro Jr. M. , Guarro J.
Published: April 2003

Background: A reference method for dermatophyte in vitro susceptibility testing is lacking. With the advent of new antimycotics, susceptibility testing has received increasing attention as an important laboratory tool for aiding the selection of appropriate drug therapy. Methods: One hundred strains of Trichophyton rubrum were tested against four antifungal agents, itraconazole, clotrimazole, ketoconazole and terbinafine, by using a modification of the proposed standard M38-P of the National Committee for Clinical Laboratory Standards and two types of standardized inocula, 1.4 × 104 and 5 × 103 CFU/ml. Results: Terbinafine was revealed to be the most effective antifungal drug. Of the three azole derivatives tested, clotrimazole showed the highest antifungal activity, while the minimum inhibitory concentrations (MICs) of itraconazole and ketoconazole were similar. Inoculum size did not affect the MIC of any of the antifungal agents tested. Conclusion: Our preliminary data provide promising results for the development of a reference method for dermatophyte susceptibility testing based on the microdilution technique, although more dermatophytes should be tested and the method evaluated in different laboratories.
Indomethacin Interferes with EGF-Induced Activation of Ornithine Decarboxylase in Gastric Cancer Cells
Authors: Ishikawa T. , Ichikawa Y. , Tarnawski A. , Fujiwara Y. , Fukuda T. , Arakawa T. , Mitsuhashi M. , Shimada H.
Published: April 2003

Background/Aims: Epidermal growth factor (EGF) has a wide variety of biological activities in the protection of gastric mucosa against acute injury and the healing of gastric ulcer. However, the molecular basis of the EGF action remains unknown. EGF-induced activation of ornithine decarboxylase (ODC) was examined, because ODC is a key enzyme for the cell proliferation. Methods: The effects of epidermal growth factor (EGF) and indomethacin on ornithine decarboxylase (ODC) mRNA and enzyme activity were examined in gastric cancer derived KATO-III cells. Results: EGF induced both ODC mRNA expression and enzyme activation in a biphasic manner with the peaks at 0.5 and 3 h for mRNA and at 5 and 9 h for enzyme activity, respectively. Indomethacin pretreatment significantly reduced EGF-induced ODC activation and was completely abolished for the first 5 h. Conclusion: Since it has been reported that both EGF and ODC are involved in cell migration and proliferation, two actions of EGF for gastric mucosal healing may be through, at least in part, this biphasic activation of ODC. Indomethacin suppresses and changes the response of ODC induced by EGF.
Immunohistochemical Characterization of the Pancreatic Cellular Infiltrate in Normal Pancreas, Chronic Pancreatitis and Pancreatic Carcinoma
Authors: Emmrich Jörg , Weber Inge , Nausch Monika , Sparmann Gisela , Koch Klaus , Seyfarth Michael , Löhr Matthias , Liebe Stefan
Published: April 2003

Background/Aims: Chronic pancreatitis is histologically characterized by an extended fibrosis and infiltration of leukocytes. We intended to differentiate the infiltration to evaluate the inflammatory process. Methods: Samples of tissues of normal pancreas (NP, n = 12), of chronic pancreatitis (CP, n = 7), and pancreatic tissues surrounding pancreatic carcinoma (CA, n = 7) were investigated by immunohistochemical staining using the APAAP technique. Results: In normal pancreas, mononuclear cells (47.1 ± 26.0 cells/mm2) were observed with a predominance of macrophages (56.3%) and T lymphocytes (31.3%) which were differentiated in CD8+ lymphocytes (9.3 ± 7.2 cells/mm2) and CD4+ lymphocytes (6.7 ± 3.2 cells/mm2). Rarely, plasma cells (5.3%) and B lymphocytes (7.1%) could be detected. In pancreatic tissue of patients with CP and in CA there was a significant increase of mononuclear cells to 264.4 ± 120.3 cells/mm2 and 284.3 ± 67.8 cells/mm2, respectively. In both diseases percentages of T lymphocytes (CP: 50.5%; CA: 48.1%) were higher than in normal controls. CD4+/CD8+ ratio of 0.77 in CP and 0.82 in CA demonstrated a predominance of CD8+ cells compared to the peripheral blood. In NP and CA, nearly all T lymphocytes expressed CD45R0 identifying memory cells, while only 58% of T lymphocytes were CD45R0 positive in CP. Conclusion: Our data suggest that the investigated cases of CP were of a common inflammatory type rather than due to an autoimmunological reaction. CD8+ T lymphocytes were the predominant T cell subset in the inflammatory infiltrates in both CP and CA.
Changes in Professional Development
Authors: Meryn Siegfried
Published: April 2003

Recent changes in society, the practice in medicine, the health care delivery and new technologies will have a direct impact on the development of the medical profession. Thus, there is a need for more efficient, evidence-based and evaluated continuing medical education (CME) programs. But CME in one’s own speciality interest is not enough. CME has to be extended into a broader context of continuing professional development (CPD) including personal, social and political aspects of medical practice. New methods have to concentrate on adult learning principles, individual needs and self-directed learning and have to promote performance-based assessment, outcome evaluation, communication skills, patient education and the use of computers and telecommunication technologies. All principles have to begin before entering medical school and then be continued and supported through a new medical curriculum from undergraduate to postgraduate training according to the ‘lifelong learning’ principle. All honorable gastroenterology, hepatology and endoscopy societies throughout the world should further define professionalism and develop leadership and management programs for their members. Nevertheless, every doctor always has a personal responsibility for lifelong learning.
Medical Therapy of Inflammatory Bowel Disease
Authors: Rutgeerts Paul
Published: April 2003

In the past years the advances in therapy of IBD have been characterized mainly by the more widespread use of immunosuppression. Especially azathioprine is currently used in Crohn’s disease with methotrexate as the second-line immunosuppressive drug. Cyclosporin may become a drug of choice to treat severe ulcerative colitis but its effect in the long term is probably insufficient. Topically acting glucocorticosteroids have emerged as a valuable safer alternative to standard glucocorticosteroids (GCS) in right ileocolonic Crohn’s disease but GCS have no role in maintenance therapy. The most significant development in recent years is the introduction of immunomodulatory treatments using cytokines and anticytokines. The first data show that anti-TNF monoclonal antibodies, especially cA2, not only may result in rapid control of active Crohn’s disease but also achieve rapid tissue healing. Repeated administration of cA2 maintains remission. Immunomodulation therapy creates great expectations since early reset of the immunostat might be able to control inflammation in the long term. Safety will be a key issue.
Endoscopic Diagnosis and Treatment of Early Cancer in the Alimentary Tract
Authors: Yoshida Shigeaki
Published: April 2003

Due to the recent widespread use of detailed endoscopy together with careful scrutiny of the mucosa using dye-spraying techniques, there has been a general acceptance in Japan that early malignancies in the alimentary tract may not appear polypoid or ulcerative. Regardless of organ, superficial early cancers have been reported. These lesions appear as faint mucosal irregularities or discolorations, which may be difficult to distinguish from nonspecific inflammation or trauma. The recognition of these malignancies has prompted the development of new techniques for their treatment. Endoscopic mucosal resection (EMR) which can resect lesions as completely as specimens removed at open surgery, has become the first choice of treatment for early digestive cancer. The lesions that can be removed by EMR should be those which hardly ever carry lymph node metastases. Endoscopically, they are shown to be flat esophageal cancers, gastritis-like cancers and colorectal cancers less than 2 cm in flat elevated type or less than 1 cm in depressed type. In spite of the advances in characterizing early cancers and an emerging consensus on indications and contraindications for EMR, much work remains to be done. New techniques will continue to push the limits of what can be achieved via an endoscope.
Cystic Fibrosis: Present and Future
Authors: Milla P.J.
Published: April 2003

Cystic fibrosis (CF) is an inherited disorder of epithelial chloride transport affecting primarily pancreas, lungs, gut, liver and exocrine glands. The defect is caused by defects of the cystic fibrosis transmembrane regulation gene on chromosome 7. Genotyping has proved useful in identifying gene carriers, a definitive diagnosis, and in antenatal diagnosis. Genotype/phenotype relationships have shown that the commonest cause of pancreatic insufficiency is the D F508 mutation. Clinical trials are exploring the use of somatic gene therapy but this is not yet a viable treatment option. Liver, lung and intestinal disease result in malnutrition which causes further dysfunction of these organs. Aggressive nutritional and pancreatic enzyme therapy results in improved disease, normal growth and increased survival. However, high-dose enzyme therapy may in some individuals cause a fibrosing colonopathy. For those with end-stage liver and lung disease, transplantation holds out some hope.
Secretin and Gastric Lipase Secretion
Authors: Olsen Ole , Wøjdemann Morten , Berner Belinda , Christiansen Gunvor , Sternby Berit
Published: April 2003

Background: Gastric lipase secretion is stimulated by gastrin in plasma, but its regulation by secretin is unknown. Methods: In 7 normal persons we investigated the effect of exogenous secretin on the output of gastric lipase stimulated by intravenous gastrin-17. The gastric content was measured using a nasogastric tube for aspiration. The quantitative lipase secretion was measured by an enzyme-linked immunosorbant assay (ELISA) and the lipolytic activity by a kinetic assay. Plasma concentrations of secretin and gastrin were measured by radioimmunoassay. Results: Gastric lipase secretion (the quantity as well as the lipolytic activity) was significantly stimulated by gastrin. In response to secretin infusion, the lipolytic activity increased as acid secretion decreased. Conclusion: Secretin in postprandial concentrations does not influence the quantitative gastric lipase secretion stimulated by gastrin, but it increases lipolytic activity due to inhibition of acid secretion.
Mucin Content in Gallbladderswith Brown Pigment Stones orCombination Stones with a Brown Periphery
Authors: Sheen Pai-Ching , Lee King-Teh , Yueh-Er Liu Y.-E.
Published: April 2003

Background/Aims: Gallbladder mucus itself has been recognized to play an important role in gallstone development. Despite the diverse mechanisms of stone induction and the differences in stone composition, there is a quantitative increase in the epithelial mucus production period before stone formation. As brown pigment stones are found frequently in gallstone disease, we conducted a study on gallbladders with brown pigment stones or combination stones with a brown periphery to evaluate the mucin content in the gallbladder epithelium in comparison to gallbladders with cholesterol stones and those without stones. Methods: Gallbladder specimens were fixed in 10% formalin immediately after cholecystectomy and then embedded in paraffin. The specimens were sectioned for periodic acid-Schiff-alcian blue (PAS-AB, pH 2.5) double stain to evaluate the intra-epithelial mucin content. The PAS-AB index was calculated as a proportion of the PAS-AB-positive mucin area to the total epithelial area, using a computerized image analyzer. Results: Evaluation of the PAS-AB index on the lining epithelia of gallbladders showed that it was 32.43 ± 9.96% in gallbladders with brown stones, which is significantly (p < 0.001) higher than in gallbladders with cholesterol stones (15.63 ± 6.75%) and gallbladders without stones (9.55 ± 4.77%). Conclusion: The results show that gallbladders with brown stones contain more abundant mucin than gallbladders with cholesterol stones or those without stones. They also suggest that the gallbladder epithelium per se might play a more important role in stone formation in those with brown stones than in those with cholesterol stones.
Effect of Copper, Cadmium, Mercury, Manganese and Lead on Fe2+ and Fe3+ Absorption in Perfused Mouse Intestine
Authors: Iturri Sergio , Nuñez Marco Tulio
Published: April 2003

Body iron homeostasis is maintained by the regulation of iron absorption in the first portion of the small intestine. Previous studies have shown that some trace metal cations may have an inhibitory effect on inorganic iron absorption. In view of the possible nutritional and toxicological implications of this inhibition, we decided to study the effect of Cu2+, Cd2+, Hg2+, Pb2+, and Mn2+ on Fe2+ and Fe3+ intestinal uptake. To that end, the duodenal portion of the mouse intestine was perfused with 1 µM 55Fe either in the 2+ or 3+ redox state, in the absence or presence of a 10-fold molar excess of Cd2+, Cu2+, Hg2+, Mn2+, or Pb2+. It was found that Cd2+ and Cu2+, but not Hg2+, Mn2+, or Pb2+, significantly inhibited the uptake of Fe2+ (p < 0.001). Surprisingly, the observed inhibition by Cu2+ and Cd2+ was dependent on the iron redox state, since neither cation inhibited Fe3+ uptake by mouse duodenum. Similarly, no inhibition of Fe3+ uptake was observed with a 10-fold molar excess of Hg2+, Mn2+, or Pb2+. These results indicate that inhibition of iron uptake by Cu2+ and Cd2+ takes place only in a reducing environment. Therefore, under the common oxidative conditions found in nutrients no inhibition of non-heme Fe uptake by Cu2+ and Cd2+, as well as Mn2+, Hg2+ and Pb2+ is to be expected. We propose either that Fe2+ and Fe3+ are transported through two different mechanisms, or that the enterocyte-mediated reduction of Fe3+, and the ensuing transport of Fe2+ are processes coupled in such a way that they are refractory to inhibition by Cu2+ and Cd2+.
GLP-1 Release in Man after Lower Large Bowel Resection or Intrarectal Glucose Administration
Authors: Printz H. , Reiter S. , Samadi N. , Ebrahimsade S. , Kirchner R. , Arnold R. , Göke B.
Published: April 2003

Background: This study addresses the question whether the insulinotropic gut hormone, glucagon-like peptide-1 (GLP-1), is released from the lower large bowel upon oral or rectal glucose uptake. Methods: It was evaluated whether rectum or sigmoid colon resection alters glucose homeostasis or the plasma levels of the insulinotropic gut hormone, gastric inhibitory polypeptide (GIP), or GLP-1. Six men and 3 women (age 63 ± 8 years, BMI 25.4 ± 4.0 kg/m2) with normal preoperative fasting glucose values were treated before and after resection of large bowel segments. Fasting oral glucose tolerance (OGT, 75 g glucose/300 ml) tests were performed both before and 10 days postoperatively. Another approach aimed to clarify whether luminal glucose stimulation in the rectum/sigmoid colon increases GLP-1 plasma levels. Ten healthy volunteers (4 males, 6 females, age 25 ± 2 years, BMI 22.1 ± 2.4 kg/m2) received enemas with both saline and, 7 days later, 1 g/kg body weight glucose (70% glucose solution) intrarectally. Results: Neither rectum nor sigmoid colon resection led to significant changes in the pre- and postoperative glucose responses to OGT testing, or insulin, GIP and GLP-1 release. Intrarectal glucose instillation increased blood glucose by about 10 mg/dl with parallel small elevations in immunoreactive insulin and immunoreactive C peptide. However, plasma GLP-1 levels remained unaltered. Conclusion: Our data make it unlikely that GLP-1 derived from the lower large bowel contributes significantly to maintain normal glucose tolerance.
Effect of Distension of the Pharynx and Esophagus on the Stomach in Dogs: Experimental Evidence for a Pharyngoesophagogastric Reflex
Authors: Shafik Ahmed
Published: April 2003

Purpose: To study the effect of pharyngeal and esophageal distension on the pressure within the stomach aiming at assessing the stomach condition during passage of food boli through the pharynx and esophagus. Methods: 12 dogs (mean weight 16.2 ± 3.3 kg) were studied. With the animal under anesthesia, a 4-Fr manometric catheter was introduced into the stomach and a 2-Fr balloon-tipped catheter into the pharynx. The gastric pressure response to pharyngeal and esophageal distension, each at a time, was recorded. Distension was performed in increments of 2 ml of water up to 6 ml. The test was repeated while the pharynx, esophagus or stomach were separately anesthetized using 2% xylocaine. Bilateral truncal vagotomy was done in 4 dogs and the gastric response to pharyngoesophageal distension studied. Results: Pharyngeal distension produced a significant pressure drop of the corpus of the stomach (p < 0.05); the pyloric antrum showed no response. Upper, middle or lower esophageal distension produced gastric response similar to that evoked by pharyngeal distension. The gastric response was abolished on distension of the anesthetized pharynx or esophagus, when the corpus was anesthetized, or after bilateral vagotomy. Conclusion: The proximal gastric dilatation on pharyngeal and esophageal distension postulates a reflex relationship between the two actions which we call ‘pharyngoesophagogastric reflex’. This reflex is suggested to dilate the proximal stomach preparatory to receiving food boli from the esophagus; it was abolished after anesthetizing its possible two arms arising from the pharyngoesophagus and the stomach, or after vagotomy.
Water Extracts of Helicobacter pylori Delay Healing of Chronic Gastric Ulcers in Rats: Role of Cytokines and Gastrin-Somatostatin Link
Authors: Brzozowski Tomasz , Konturek Peter C. , Konturek Stanislaw J. , Kwiecien Slawomir , Pajdo Robert , Karczewska Elzbieta , Stachura Jerzy , Hahn Eckhart G.
Published: April 2003

Background: Helicobacter pylori (Hp) is considered as a major risk factor of peptic ulcer, but the pathogenic mechanism of its action has not been fully explained. Aims: This study was designed: (1) to compare the ulcer healing effects of water extract (WE) obtained from type-I cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) expressing Hp and from type-II CagA- and VacA-negative Hp strain with those of vehicle (saline), and (2) to determine the alterations in gastric secretion, gastric blood flow (GBF) and expression of Hp-related cytokines during the ulcer healing in rats treated with toxigenic (type-I) and non-toxigenic (type-II) Hp-derived WE. Methods: Gastric ulcers were produced by serosal application of acetic acid in rats with or without gastric fistula treated with vehicle (saline) or WE originating from type-I or type-II Hp administered intragastrically on days 1, 3, 5 and 7 upon ulcer induction. On days 3, 9 and 15, animals were lightly anesthetized with ether, the abdomen was opened and the GBF was measured by the H2-gas clearance technique in the ulcer area and non-ulcerated mucosa. Venous blood was withdrawn for the measurement of plasma cytokine (IL-1β and TNFα) levels and plasma and gastric contents were also collected for gastrin and somatostatin determination by specific radioimmunoassay. Results: Gastric ulcers healed gradually in vehicle-treated controls and the ulcer area on days 3, 9 and 15 was reduced by 12, 43 and 92%, respectively. In rats treated with WE of type-I Hp, ulcer healing was significantly delayed, and gastritis and infiltration of ulcerated gastric mucosa with inflammatory cells were observed histologically. The prolongation of ulcer healing by WE of both Hp strains was accompanied by a marked fall in the GBF at the ulcer margin and transient hyposecretion especially in rats given WE of type-I Hp strain. On day 15 of ulcer healing, the plasma concentration of IL-1β and TNFα was negligible in vehicle control rats, but it was significantly elevated particularly in rats treated with WE of type-I Hp. RT-PCR analysis revealed that mucosal expression of IL-1β and TNFα mRNA was significantly upregulated in the gastric mucosa of rats treated with either toxigenic or non-toxigenic Hp WE. The plasma gastrin level was significantly higher and the luminal concentration of somatostatin was significantly lower in rats treated with Hp-WE than in vehicle-treated controls and these alterations were more pronounced in rats treated with WE type-I than type-II Hp. Conclusions: WE of toxigenic Hp strain delays ulcer healing due to the reduction in the gastric microcirculation at the ulcer margin, the overexpression of inflammatory cytokines and the impairment of the gastrin-somatostatin link.
Continuous Intravenous Octreotide Treatment for Acute Experimental Pancreatitis
Authors: Greenberg R. , Haddad R. , Kashtan H. , Brazowski E. , Graff E. , Skornick Y. , Kaplan O.
Published: April 2003

Background: The efficacy of octreotide, the synthetic analogue of the hormone somatostatin, for the treatment of acute pancreatitis is controversial. Octreotide has been commonly administered in subcutaneous bolus injections; however, continuous intravenous infusion may be advantageous for acute conditions. Methods: Acute experimental pancreatitis was induced in rats by intraparenchymal injections of 1 ml 10% sodium taurocholate, and octreotide (1 µg/kg/h, dissolved in physiological solution, intravenously was started 4 h later and continuously infused for 48 h. Physiological solution infusions, in identical volumes, were used in the controls. The following parameters were examined: mortality; macroscopic and histological damage; hematocrit; plasma pH; acid-base balance; serum glucose; calcium, and amylase. Results: Octreotide treatment had a striking effect on mortality: 8.3 versus 91.6% in the treatment and control groups, respectively (p < 0.001). Octreotide also ameliorated pancreatic edema and intestinal dilatation, and had significant beneficial effects on histopathological damage and the biochemical alterations which are associated with acute pancreatitis. Conclusions: Continuous intravenous octreotide infusion is a potentially efficacious therapeutic method for acute pancreatitis.
Regulation of the Actin Cytoskeleton by p125 Focal Adhesion Kinase in Rat Pancreatic Acinar Cells
Authors: Kiehne Karlheinz , Herzig Karl H. , Fölsch Ulrich R.
Published: April 2003

Background/Aims: Activation of p125 focal adhesion kinase by cholecystokinin (CCK)-8 has recently been demonstrated in pancreatic acinar cells. The purpose of this study is to examine downstream events of this kinase. Methods: Activation of p125 focal adhesion kinase in freshly isolated rat pancreatic acinar cells was determined by Western blot analysis. Actin cytoskeletal changes were visualized on TRITC-phalloidin-stained cryosections. Amylase release was measured by colorimetric assay. Results: CCK-8 caused dose-dependent activation of p125 focal adhesion kinase. Time-course analysis showed rapid activation with maximum between 5 and 10 min and stimulation still detectable after 60 min. Preincubation with 2 µM cytochalasin D specifically inhibited p125 focal adhesion kinase, but not p42 mitogen-activated protein kinase or increases in intracellular calcium concentrations. The actin cytoskeleton showed rapid reorganization after stimulation, with an initial increase in fluorescence followed by a decline after 30 min. Preincubation with cytochalasin D prevented cytoskeletal changes. Amylase release at concentrations up to 0.1 nM CCK-8 was not influenced by cytochalasin D. In contrast, supramaximal inhibition of amylase release was less pronounced after cytochalasin D incubation. Conclusion: p125 focal adhesion kinase in acinar cells appears to be part of a signalling pathway leading to changes in cellular morphology via the actin cytoskeleton. Maximal activation of this signalling pathway might participate in supramaximal inhibition of enzyme secretion.
Embryology of the Pancreatic Duct System
Authors: Kamisawa Terumi , Koike Morio , Okamoto Atsutake
Published: April 2003

Background/Aims: It has been suggested that the distal portion of the dorsal pancreatic duct and the ventral pancreatic duct usually merge into the main pancreatic duct, and the proximal portion of the dorsal pancreatic duct becomes the accessory pancreatic duct. In this study, we investigated the embryology of the accessory pancreatic duct roentgenographically and immunohistochemically. Methods/Results: The accessory pancreatic duct shows two different patterns in pancreatograms: the long and the short type. The accessory pancreatic duct of the long type forms a straight line and joins the main pancreatic duct at the neck portion of the pancreas. The accessory pancreatic duct of the short type joins the main pancreatic duct near its first inferior branch. Long inferior branches from the accessory pancreatic duct were found in 74.6% with the long type, significantly more often than in the short type (29.3%). Patency of the long type was (74.5%) significantly greater than in the short type (36.2%). Immunohistochemically, we found the main pancreatic duct between the junction with the accessory pancreatic duct and the neck portion of the autopsy pancreas in the short type was located within the ventral pancreas, characterized by pancreatic polypeptide-rich islets. Conclusion: The long type represents a continuation of the main duct of the dorsal primordium. The short type is very likely formed by the proximal main duct of the dorsal primordium and its long inferior branch, with the main duct of the dorsal primordium at the point of connection with the main duct of the ventral primordium being obliterated and replaced by this additional communication.
Impacted Papilla Minor Stone in Pancreas divisum Causing Severe Acute Pancreatitis
Authors: Renzulli Pietro , Müller Christoph , Uhl Waldemar , Scheurer Ulrich , Büchler Markus W.
Published: April 2003

This is the first description of severe acute pancreatitis in pancreas divisum caused by a solitary stone impacted in the minor papilla. Recovery was rapid after diagnostic endoscopic retrograde cholangiopancreaticography (ERCP) and endoscopic stone removal. Since other etiological factors accounting for the acute pancreatitis were carefully excluded, it seems that obstruction of the minor papilla by a solitary pancreatic concrement was the most likely cause of acute pancreatitis. This case report demonstrates the diagnostic importance of early ERCP in cases of etiologically unexplained acute pancreatitis.
Aspiration: A Possible Severe Complication in Colonoscopy Preparation of Elderly People by Orthograde Intestine Lavage
Authors: Gabel Andreas , Müller Stefan
Published: April 2003

Total gut lavage is a widely recommended method in preparation for colonoscopy and there are almost no reports of severe complications in the literature. Application of orthograde lavage by a nasogastric tube may be necessary in disorientated patients, assisted by slight medical sedation, if necessary. Despite absolutely correct appliance of the method, a case of severe aspiration with subsequent hypoxemia and stroke in a senile female patient, suffering from a common hiatal hernia, is described.
Effect of Chain Length on Absorption of Biologically Active Peptides from the Gastrointestinal Tract
Authors: Roberts Pamela R. , Burney J.D. , Black Kimberly W. , Zaloga Gary P.
Published: April 2003

Objectives: Protein digestion generates many peptides in the gut lumen. Some of these peptides possess biological effects when tested using in vitro systems. It is clear that dipeptides and tripeptides can be absorbed intact from the gastrointestinal tract. However, the fate of larger peptides and small proteins remains unclear. Equally unclear are the biologic potencies of absorbed peptides and the quantity of peptide that must be administered into the gut to produce a biologic effect. Thus, the purpose of this study was to determine the effect of amino acid chain length on the ability of enterally administered peptides to produce biologic effects. Methods: Small bowel feeding tubes, jugular catheters, and arterial lines were placed into adult male Sprague-Dawley rats. Rats were administered intravenous (50 μg) and enteral (125 and 500 μg) thyrotropin-releasing hormone (TRH, a tripeptide), intravenous (100 μg) and enteral (100 and 500 μg) luteinizing hormone-releasing hormone (LHRH, a decapeptide), and intravenous (0.5 mg) and enteral (0.5 and 25 mg) insulin (a 51-amino acid polypeptide). The quantity of peptide administered represented less than 0.5% of a rat’s normal daily protein intake. The biologic effect of TRH, LHRH, and insulin were assessed using thyroid-stimulating hormone (TSH) response, follicle-stimulating hormone (FSH) response, and glucose. We also measured serum levels of insulin in the rats following enteral insulin administration. Results: The results indicate that enteral TRH (125 and 500 μg) produced the same TSH response as intravenous TRH. The response to 500 μg enteral LHRH was 50% of the response to intravenous LHRH and the response to 25 mg enteral insulin was 30% of the response to 0.5 mg intravenous insulin. Serum insulin levels increased significantly following both 0.5 and 25 mg enteral insulin. Conclusions: These results support the concept that small (di- and tripeptides) and large (10–51 amino acids) peptides generated in the diet can be absorbed intact through the intestines and produce biologic effects at the tissue level. The potency of the enterally administered peptides decreases as the chain length increases. We postulate that absorbed dietary peptides play a role in the modulation of organ function and disease progression.