bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Sub-Minimum Inhibitory Concentrations of Cefodizime on the Phagocytosis, Intracellular Killing and Oxidative Bursts of Human Polymorphonuclear Leukocytes
Authors: Braga P.C. , Dal Sasso M. , Mancini L. , Sala M.T. 
Published: April 2003

It is generally recognized that sub-minimum inhibitory concentrations (sub-MICs) of antibiotics are still capable of interfering with some bacterial virulence parameters, thus facilitating host neutrophilic defenses such as phagocytosis, killing and oxidative bursts. This study investigated the interaction of <i>Escherichia coli</i> with these neutrophilic functions after pretreatment with various sub-MICs of cefodizime. <i>E. coli</i> exposed to 1/2 to 1/8 MICs of cefodizime showed the extensive production of long and very long filaments that interfere with the precise measurement of phagocytic and killing parameters. Our analysis was consequently extended to the activity of 1/16 to 1/64 MICs. The interesting finding was that, although phagocytosis was unaffected, killing was significantly increased in one strain at 1/16 MIC and in another at 1/32 MIC while in the last strain it was unaffected. Oxidative bursts were not modified by any of the sub-MICs. The knowledge that these sub-MICs are still effective in increasing bacteria killing, correlated with the pharmacokinetic curve of a common single dose of cefodizime 1 g i.m., showed that the killing effects of sub-MICs may last for as long as 12 h after the activity of the MIC value. This integrated information extends our knowledge of the ultimate efficacy of an antibiotic and provides further information for optimizing scheduling.
Intrapleural Administration of Cisplatin and Etoposide to Treat Malignant Pleural Effusions in Patients with Non-Small Cell Lung Cancer
Authors: Tohda Yuji , Iwanaga Takashi , Takada Minoru , Yana Takashi , Kawahara Masaaki , Negoro Shun-ichi , Okishio Kyoichi , Kudoh Shinzo , Fukuoka Masahiro , Furuse Kiyoyuki 
Published: April 2003

<i>Background:</i> To determine the efficacy, toxicity and pharmacokinetics of intrapleural cisplatin (CDDP) and etoposide as a treatment for malignant pleural effusions (MPE) in patients with non-small cell lung cancer (NSCLC). <i>Methods:</i> Seventy patients with MPE associated with NSCLC were enrolled in this study. In 68 patients, a catheter was inserted into the pleural cavity, within 24 h after complete drainage of the pleural effusion, CDDP (80 mg/m<sup>2</sup>) and etoposide (80 mg/m<sup>2</sup>) were simultaneously administered successfully via the catheter and the catheter was clamped. Seventy-two hours later, the catheter was unclamped to allow drainage. The catheter was removed when the accumulated intrapleural fluid decreased to 20 ml or less per day. <i>Results:</i> The pharmacokinetic profiles showed high maximum concentrations of CDDP (free form, 88 µg/ml) and etoposide (182.4 µg/ml) in intrapleural fluids. CDDP did not remain for a long period (free form, β-phase half-life = 10.51 h) in the fluids, while etoposide persisted for a long period (β-phase half-life = 62.53 h). The overall response rate was 46.2%, the median survival time 32.3 weeks, the 1-year survival rate 28.7% and the 2-year survival rate 12.8%. The most serious adverse reactions were WHO grade 3 anemia (3 patients), grade 3 nausea and vomiting (17 patients), grade 3 constipation (1 patient), grade 3 pulmonary toxicity (1 patient), grade 4 fever (1 patient), grade 3 infection (1 patient) and grade 3 mental disorder (1 patient). <i>Conclusion:</i> Intrapleural administration of CDDP and etoposide was an effective and acceptable regimen for patients with MPE due to NSCLC.
In vitro Bactericidal Activities of a New Oral Cephalosporin, E1100, and Morphologic Changes on <i>Escherichia coli</i>
Authors: Mikamo Hiroshige , Satoh Masaru , Kai Jyunko , Sato Yasumasa , Hayasaki Yoh , Tamaya Teruhiko 
Published: April 2003

<i>Escherichia coli</i> is one of the most common aerobic bacteria in pelvic inflammatory diseases. Oral cephalosporins have been widely used against those infections. We investigated in vitro morphologic changes induced on <i>E. coli</i> by a new oral cephalosporin, E1100, and its bactericidal activity on this organism. Morphologic changes were observed by electron microscopy. E1100 induced morphologic changes (filamentation) and exerted a bactericidal activity on <i>E. coli</i>. The filamentation induced by E1100 was time and concentration dependent.
Nitazoxanide, a Nitrothiazolide Antiparasitic Drug, Is an Anti-<i>Helicobacter pylori</i> Agent with Anti-Vacuolating Toxin Activity
Authors: Yamamoto Yoshimasa , Hakki Amal , Friedman Herman , Okubo Sachie , Shimamura Tadakatsu , Hoffman Paul S. , Rossignol Jean-François 
Published: April 2003

Nitazoxanide (NTZ), a synthesized drug of the nitrothiazolide class, was initially developed as an antiparasitic compound. This compound has recently been shown to have antibacterial activities against some bacterial pathogens. In the present study, NTZ and its main metabolite tizoxanide (TIZ) were found to have strong minimum inhibitory concentrations (MICs) against both metronidazole (MTZ)-resistant strains and sensitive clinical isolates of <i>Helicobacter pylori</i>. The MIC<sub>90</sub> of both NTZ and TIZ against 37 clinical isolates was 8 μg/ml. Vacuolating toxin activity of <i>H. pylori</i> assayed by HeLa cell vacuole formation was inhibited by NTZ at a sub-MIC. In contrast, urease production by <i>H. pylori</i> was not specifically affected by the sub-MIC of NTZ. An acidic pH (pH 5.0) medium reduced the antimicrobial activity of the drug in terms of growth inhibition due to the low growth rate of the bacteria, but killing activity of NTZ against the bacteria was still observed. Thus, it was apparent that both NTZ and TIZ are highly effective against <i>H. pylori</i>, even when the bacteria are resistant to MTZ.
Lack of Pharmacokinetic Interaction between Gemifloxacin and Digoxin in Healthy Elderly Volunteers
Authors: Vousden Marika , Allen Ann , Lewis Anastasia , Ehren Norbert 
Published: April 2003

Gemifloxacin is a novel fluoroquinolone with a broad spectrum of antibacterial activity. The objective of this double-blind, randomized, placebo-controlled, 2-way crossover study was to demonstrate the lack of a pharmacokinetic interaction between gemifloxacin and digoxin. During two 14-day treatment periods, healthy elderly volunteers received digoxin (0.25 mg, once daily) co-administered on days 8–14 with either gemifloxacin (320 mg, p.o., once daily) or placebo. On day 14 of each period, blood samples and urine were collected for 24 h post dose and analysed for digoxin levels by radioimmunoassay. Steady-state digoxin pharmacokinetics were not affected by multiple dosing with gemifloxacin. There was no significant difference in digoxin values for the area under the plasma concentration-time curve over the dosing interval 0–24 h (AUC<sub>(0–24)</sub>) or the trough plasma concentration (C24) after co-administration with either gemifloxacin or placebo. Geometric means for AUC<sub>(0–24)</sub> and C24 were 18.1 and 17.8 ng·h/ml and 0.597 and 0.566 ng/ml, respectively. The point estimates (90% confidence intervals) for AUC<sub>(0–24)</sub> and C24 (digoxin + gemifloxacin):(digoxin + placebo) were 1.01 (0.93, 1.10) and 1.05 (0.95, 1.16), respectively, entirely within the equivalence range (0.80, 1.25). There were no marked differences between co-administration regimens for maximum observed plasma concentration (C<sub>max</sub>) or renal clearance values. Gemifloxacin was well tolerated during co-administration with digoxin, and the incidence of adverse events was similar to that seen with placebo. There were no clinically relevant changes in vital signs, electrocardiogram readings or laboratory parameters. In conclusion, this study demonstrates that gemifloxacin may be co-administered with digoxin without the need for digoxin dose adjustment.
Fluconazole Inhibits Pseudohyphal Growth in <i>Saccharomyces cerevisiae</i>
Authors: Kontoyiannis Dimitrios P. 
Published: April 2003

The ergosterol-depleting antifungal fluconazole, when given at concentrations not affecting growth, inhibited pseudohyphal growth in <i>Saccharomyces cerevisiae</i>, a genetically tractable fungus closely related to the human pathogen <i>Candida albicans</i>. These results suggest that <i>S. cerevisiae</i> 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 <i>Pseudomonas aeruginosa</i> 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 <i>Pseudomonas aeruginosa</i> 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 AUC<sub>0–∞</sub> 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.
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

<i>Background:</i> Although postoperative infections continue to be a major problem in gynecologic surgery, there is still no consensus on the efficacy of antibiotic prophylaxis. <i>Methods:</i> 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. <i>Results:</i> 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). <i>Conclusion:</i> 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.
In vitro Activity of Ceftazidime, Cefepime and Imipenem on 1,005 <i>Pseudomonas aeruginosa</i> Clinical Isolates either Susceptible or Resistant to Beta-Lactams
Authors: Bonfiglio Giovanni , Marchetti Federico 
Published: April 2003

<i>Background:</i> Recently, new ‘fourth-generation’ cephalosporins, such as cefepime and cefpirome, were introduced into antibacterial chemotherapy. <i>Methods:</i> In order to explore whether these new cephalosporins offer real advantages against <i>Pseudomonas aeruginosa,</i> we matched the in vitro activity of cefepime with that of ceftazidime and imipenem as reference compounds. <i>Results:</i> 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 <i>P. aeruginosa</i> 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. <i>Conclusion:</i> Ceftazidime and imipenem retained their activity against the majority of clinical <i>P. aeruginosa</i> isolates collected in Italy. Cefepime did not offer competitive advantages in terms of in vitro activity.
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 <i>Streptococcus pneumoniae</i>, group A β-hemolytic <i>Streptococcus pyogenes</i>, <i>Moraxella catarrhalis</i> and <i>Haemophilus influenzae</i>, 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 <i>H. influenzae</i> resistant to CLA and AZI. An increase in MICs was observed against <i>S. pyogenes</i> and <i>H. influenzae</i>, with higher values for AZI.
Anastomotic Blood-Flow Reduction in Rat Small Intestine with Chronic Radiation Damage
Authors: Jahnson S. , Holtz A. , Gerdin B. 
Published: April 2003

<b>Background/Aims: </b>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. <b>Method: </b>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 <sup>14</sup>C-iodoantipyrine autoradiography technique in 16 sectors around the circumference both in the anastomotic segment and in a segment 4 mm apart. <b>Results: </b>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). <b>Conclusions: </b>The results favor the hypothesis that anastomoses in previously irradiated intestine are vascularly compromized and thereby have an increased risk of leakage.
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

<b>Background:</b> 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. <b>Materials and Methods:</b> 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. <b>Results:</b> 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. <b>Conclusion:</b> 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.
Ischemia-Reperfusion-Induced Delay in Intestinal Transit
Authors: Alican İnci , Yegen Cumhur , Olcay Ayhan , Kurtel Hızır , Yegen Berrak Ç. 
Published: April 2003

<b>Background/Aims:</b> To evaluate the involvement of ET-1 in ischemia-reperfusion (I/R) injury. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusion:</b> The results of the present study imply that I/R delays intestinal transit involving an endothelin-dependent mechanism.
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 (I<sub>SC</sub>). Dietary adaptation led to large equivalent increments of Na and Cl net absorption without adequate I<sub>SC</sub> change. Inhibitor studies (mucosal amiloride 10<sup>–3</sup> and 10<sup>–4</sup> <i>M;</i> mucosal 4,4-diisothiocyanatostilbene-2,2-disulfonic acid 5 × 10<sup>–5</sup> <i>M;</i> serosal furosemide 10<sup>–3</sup> <i>M;</i> serosal ouabain 10<sup>–3</sup> <i>M</i>) suggested that normal cecal NaCl absorption involves electroneutral Na/H and Cl/HCO<sub>3</sub> 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.
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.