bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of the Earliest Ventricular Contraction Site in Patients with Wolff-Parkinson-White Syndrome Using Two-Dimensional Guided M-Mode Tissue Doppler Echocardiography
Authors: Nagai Hideo , Takata Shigeo , Sakagami Satoru , Furusho Hiroshi , Takamura Masayuki , Yuasa Toyoshi , Kobayashi Ken-ichi
Published: April 2003

Objective: The purpose of this study was to examine the feasibility of M-mode tissue Doppler imaging for localizing the accessory pathway in patients with Wolff-Parkinson-White (WPW) syndrome. Methods: Two-dimensional guided tissue Doppler M-mode was recorded at the mitral and tricuspid annular levels in 13 WPW patients. Time intervals were measured from the onset of the δ wave or the R wave to the beginning of the ventricular systolic motion. The earliest contraction site was defined as the site demonstrating the shortest time interval, and compared with the earliest activated site determined by body surface mapping and the successful ablation site. Results: In 6 patients with a left-sided pathway, tissue Doppler localization was identical to the ablation site. In 3 with a left-sided pathway and 3 with a right-sided pathway, localization was judged as an adjacent region of the ablation site. In 1 patient with a right lateral pathway, the pathway location was misdiagnosed. The tissue Doppler diagnosis for the left-sided pathways correlated well with the ablation site, in contrast to the right-sided pathways (p = 0.05). Prediction of the accessory pathway localization by tissue Doppler M-mode was equivalent to localization based on body surface mapping. Conclusions: In WPW syndrome, tissue Doppler M-mode can detect the earliest contraction sites and seems helpful in localizing the left-sided accessory pathways, but is of limited use for right-sided pathways.
Uni- and Bipolar Pacing Threshold Measurements with Capturecontrol, a New Automatic Pacemaker Function for Capture Verification
Authors: Schuchert Andreas , Meinertz Thomas
Published: April 2003

It is mandatory in pacemaker patients to determine the pacing threshold at each follow-up visit. To facilitate the pacing threshold measurements, complete automatic pacemaker tests are being developed. A new pacemaker algorithm for automatic capture verification (Capturecontrol) detects the presence of the evoked response signal 70–100 ms after the pacing pulse. The aim of this study was to determine the uni- and bipolar pacing thresholds using this automatic pacemaker function and compare them with the manually determined threshold. The study included 14 patients with the DDD pacemaker Logos (Biotronik) connected to the high-ohmic ventricular pacing lead Synox SX 60-BP (Biotronik). At predischarge and 8, 14, 20 and 26 weeks after implantation the uni- and bipolar pacing thresholds were assessed manually and with the automatic pacemaker function at 0.4 ms duration. Mean pacing thresholds determined with the automatic pacemaker function were not different from the manually measured values. This applied to uni- and bipolar pacing. Seventy percent of all unipolar and 67% of all bipolar measurements had no deviation. A deviation of 0.1 V between manual and automatic threshold measurement was observed in 25% (unipolar) and 28% (bipolar), respectively. A 0.2-volt difference occurred in 3% in the unipolar measurements. Deviations ≥0.3 V were found in 2% of all unipolar and in 5% of all bipolar measurements. In conclusion, automatic pacing threshold measurements using the Capturecontrol algorithm were similar compared to the manually determined thresholds. The excellent agreement between the two methods was observed for bipolar as well as unipolar pacing and on condition that all patients had a high-ohmic ventricular pacing lead. Therefore, fewer requirements are necessary for Capturecontrol than for presently available systems. Such pacemaker functions can help to speed up the measurements during follow-up visits.
Left Ventricular Pseudoaneurysm: Diagnosis by Cine Magnetic Resonance Imaging
Authors: Frances Craig D. , Shlipak Michael G. , Grady Deborah
Published: April 2003

We report a case that illustrates the difficulty in diagnosing left ventricular (LV) pseudoaneurysm and the potential value of cine magnetic resonance imaging (MRI). A 69-year-old man with a history of ischemic congestive heart failure had a mass found on routine chest X-ray, contiguous with the cardiac silhouette. Neither CT nor echocardiography accurately defined the mass. The diagnosis of LV pseudoaneurysm was definitely made by cine MRI. Although the accuracy of various imaging modalities for detecting LV pseudoaneurysm is not known, cine MRI was the most useful test in this case. Despite refusing surgery to correct the pseudoaneurysm, the patient survived for nearly 4 years, treated only with anticoagulation.
An Interleukin-6-Producing Cardiac Myxoma Associated with Mediastinal Lymphadenopathy
Authors: Takizawa Takako , Sumino Hiroyuki , Kanda Tsugiyasu , Kobayashi Isao , Nagai Ryozo , Ichikawa Shuichi
Published: April 2003

We report our experience with a patient whose mediastinal lymphadenopathy resolved after resection of a cardiac myxoma that secreted interleukin-6 (IL-6). The patient was a 68-year-old female who complained of nocturnal chest discomfort related to congestive heart failure. An echocardiogram demonstrated a large left atrial mass. A computed tomogram showed not only the left atrial mass but multiple enlarged mediastinal lymph nodes. The serum IL-6 level was markedly elevated at 13.7 pg/ml. After resection of the cardiac myxoma, serum IL-6 returned to the normal range. A repeat computed tomogram showed no mediastinal lymphadenopathy. We believe that overproduction of IL-6 by the cardiac myxoma was the cause of the mediastinal lymphadenopathy.
The Oldest Patient to Undergo Aortic Valve Replacement
Authors: Ziedalski Tomasz M. , Liebowitz Richard S. , Copeland Jack G.
Published: April 2003

As the American population ages, more elderly patients will present with significant heart disease. This group has an increase in morbidity and mortality with heart surgery as compared to a younger population. Severe aortic stenosis has a grave prognosis, and therefore surgical options should be considered even in the most elderly patient with this condition. We present the oldest reported patient to undergo aortic valve replacement for severe aortic stenosis.
Dependency of Premature Ventricular Contractions on Heart Rate and Circadian Rhythms during Childhood
Authors: Massin Martial M. , Maeyns Kristel , Withofs Nadia , Gérard Paul
Published: April 2003

The aim of the present study was to identify and quantify the rate dependence of premature ventricular contractions (PVC) during childhood. A 24-hour Holter recording was performed in 16 consecutive children, aged 22 days to 11 years (mean age 5.6 years), with frequent (>5,000/day), isolated monomorphic PVC. Those PVC were identified and the length of the preceding sinus cycle was measured. The values were ordered into 50-ms class intervals, and the percentage of PVC for each class was calculated and then analyzed by linear regression analysis. On the basis of the significance of the p value, and the positive or negative value of the slope, we identified a tachycardia-enhanced, a bradycardia-enhanced, and an indifferent pattern. Chronobiologic analysis was made by the cosinor method. All the patients had upper and lower limits of cycle length beyond which PVC disappeared. A tachycardia-enhanced pattern was present in 7 patients and an indifferent one in 9 patients. In the latter a second-degree polynomial correlation was systematically found. Children but not infants had a significant circadian variation in the frequency of PVC with a very variable time of highest incidence. In conclusion, it is possible to identify a circadian rhythm of PVC and a spontaneous trend between their incidence and the length of the preceding cardiac cycle in children.
A Randomized Crossover Evaluation of Antianginal Efficacy and Safety of Nitrolingual-Spray and Nitroglycerin Tablet Form in Coronary Artery Disease Patients
Authors: Chien Kuo-Liong , Sung Fung-Chang , Chao Chia-Lun , Su Ta-Chen , Chen Ming-Fong , Lee Yuan-Teh
Published: April 2003

Twenty-eight coronary artery disease patients with more than 50% stenosis in at least one major coronary artery completed this randomized crossover clinical trial for the comparison of efficacy and safety of Nitrolingual-Spray and nitroglycerin (NTG) tablets. Exercise time was lengthened to 399.1 s (spray) or 408.5 s (tablets), compared to a baseline of 387.3 s. Ischemic burden decreased to about –4.0 mm with both forms, compared to –7.5 mm at baseline (ANOVA: p = 0.003). The ischemic time improved to 137.2 s (spray) or 152.9 s (tablets), compared to 253.4 s at baseline (ANOVA: p = 0.005). Patients taking tablets experienced more episodes of hypotension and/or headache compared to patients taking the spray. Nitrolingual-Spray is as effective and safe as NTG tablets for the treatment of symptomatic coronary heart disease.
Left Ventricular Structure and Function in Primary Hyperparathyroidism before and after Parathyroidectomy
Authors: Näppi Satu , Saha Heikki , Virtanen Vesa , Limnell Vilho , Sand Juhani , Salmi Jorma , Pasternack Amos
Published: April 2003

Objective: Our aim was to study the effect of primary hyperparathyroidism (PHPT) and parathyroidectomy (PTX) on left ventricular (LV) wall thicknesses and systolic and diastolic function. Methods: Fifteen patients with untreated PHPT were evaluated by applying Doppler and digitized M-mode echocardiography before and 2–3 months after PTX. Fifteen age- and sex-matched healthy controls were also examined echocardiographically. Results: Prior to PTX, interventricular septal thickness (IVST), LV mass (LVM), aortic root dimension and left atrium dimension were greater and LV fractional shortening was slightly decreased in patients as compared to controls. Significantly increased LV peak late diastolic velocity (Amax) and isovolumic relaxation time, and a slightly decreased ratio of peak early to peak late diastolic velocities (E/Amax) in the patients indicated impairment of LV diastolic function in hyperparathyroidism. PTX reduced serum total Ca from 2.79 ± 0.13 to 2.39 ± 0.09 mmol/l (p < 0.001) and tended to reduce IVST [10.6 ± 2.1 vs. 10.4 ± 2.0 mm; not significant (n.s.)], LV posterior wall thickness (9.6 ± 2.0 vs. 9.2 ± 1.0 mm, n.s.) and LVM (250 ± 102 vs. 213 ± 42 g; n.s.). Before PTX, there was a significant correlation between serum total Ca and LVM (r = 0.63, p < 0.05), and the PTX-induced change in serum total calcium correlated with the change in LVM (r = 0.59, p < 0.05). PTX induced no significant changes in LV systolic or diastolic function during the follow-up of 2–3 months. Conclusions: The present findings indicate that PHPT induces LV hypertrophy, slight impairment of LV systolic function and significant impairment of LV diastolic function, which are not substantially improved after TX and 2–3 months of normocalcemia.
Temperature-Controlled High Frequency Ablation for Creation of Transmyocardial Channels: In vivo Validation of a Novel Method
Authors: Dietz Ulrich , Otto Mike , Buerke Michael , Eick Olaf , El Odhi Reza , Förderer Alp , Rippin Gerd , Kirkpatrick C. James , Meyer Jürgen , Darius Harald
Published: April 2003

Objective: We investigated the feasibility and short-term effects of a novel procedure to create intramyocardial channels by means of high frequency (HF) ablation in a rabbit in vivo model. Methods: A flexible catheter ending in a cylindrical electrode (diameter 0.7 mm) with a sharpened tip was used for HF energy application following transmyocardial insertion. Power-controlled or energy-controlled energy applications were performed in 16 anesthetized rabbits after thoracotomy with a follow-up for 3 h. Assessment of myocardial channels and the necrotic zone was performed by morphometric quantification in serial sections. The ferret diameter was used to compare channel dimensions and the extent of necrosis. Results: Thirty-nine power-controlled and 54 temperature-controlled HF applications were performed. The shape of identified channels was round in 71% and 69% had a lumen patency of ≥2/3 of the channel. Ferret diameter of the channels was 414 ± 180 μm and of the necrotic zone 3,558 ± 1,200 μm. In temperature-controlled applications, channel dimensions were strongly influenced by the maximum tissue temperature and the duration of energy delivery (Tmax: p = 0.0006; duration: p = 0.003). Channel and necrosis dimensions correlated better with biometric parameters in temperature-controlled compared with power-controlled applications. Conclusion: Mechanically created transmyocardial channels can be stabilized by HF heating of the surrounding tissue. A high percentage of these channels remain patent. The channel dimensions are closely correlated with maximum temperature and duration of energy delivery in a temperature-controlled application mode.
Effects of Long-Term/Low-Dose Clarithromycin on Neutrophil Count and Interleukin-8 Level in Pyometra
Authors: Mikamo Hiroshige , Kawazoe Kyoko , Sato Yasumasa , Tamaya Teruhiko
Published: April 2003

We investigated the effects of clarithromycin (CAM) on clinical and endometrial immune responses in chronic intrauterine infection (pyometra). CAM was orally administered in a dose of 200 mg once a day for 4 months (long-term/low-dose treatment) in patients with pyometra. Lavage fluid of the uterine endometrial cavity was obtained from 5 healthy women (controls) and 5 patients with pyometra to investigate the levels of neutrophil and interleukin-8 (IL-8), which is a neutrophil chemotactic factor. All patients showed clinical improvement at the end of treatment. In the assessment of the immune responses, neutrophils were accumulated in the lavage fluid of the uterine endometrial cavity in pyometra (p < 0.001, versus controls) and decreased by CAM treatment (p < 0.001). The level of IL-8 was significantly higher in the lavage fluid of patients with uterine endometritis than in the controls (p < 0.001), and decreased by CAM treatment (p < 0.01). There was a close correlation (r = 0.982) between neutrophil count and IL-8 level in the endometrial lavage of patients with pyometra. The reduction of the uterine endometrial neutrophil migration in chronic inflammatory sites may partially be a direct effect of CAM.
Efficacy of Amphotericin B and Azoles Alone and in Combination against Disseminated Trichosporonosis in Neutropenic Mice
Authors: Kamberi Perparim , Atsuro Hashimoto , Takayoshi Tashiro , Masaru Nasu
Published: April 2003

The activities of amphotericin B, miconazole, fluconazole, and itraconazole against Trichosporon beigelii were assessed in a mouse model of disseminated infection. Cyclophosphamide plus prednisolone-immunosuppressed ICR mice, intravenously challenged with a lethal inoculum of (6 × 106 CFU/mouse), were assigned to receive 7 days of therapy with amphotericin B (0.5 or 2 mg/kg/day), miconazole (10 or 40 mg/kg/day), fluconazole (10 or 40 mg/kg/day), or itraconazole (10 and 40 mg/kg/day). The efficacy of a combination of amphotericin B (1 mg/kg/day) with fluconazole (10 mg/kg/day) or itraconazole (20 mg/kg/day) with that of each agent alone was also compared. Both amphotericin B and azoles improved survival and reduced the fungal counts in kidneys of infected mice in a dose-dependent pattern. In general, fluconazole was superior to amphotericin B and the other azoles, whereas the latter two drugs were as effective as amphotericin B. The activity of amphotericin B combined with fluconazole appeared to be superior to that of each agent alone, especially in reducing the organ fungal burden. The other combination (amphotericin B plus itraconazole) had a weaker effect, but no antagonism was observed. In conclusion, azoles may be an alternative to amphotericin B for the treatment of T. beigelii infection. Furthermore, their combination with amphotericin B may improve the poor outcome seen in profoundly neutropenic patients with disseminated trichosporonosis.
Therapeutic Effects of Cefozopran on Polymicrobial Infections Associated with Enterococcus faecalis in a Rat Pyometra Model
Authors: Mikamo Hiroshige , Kawazoe Kyoko , Sato Yasumasa , Izumi Koji , Tamaya Teruhiko
Published: April 2003

Enterococcus faecalis plays an important role as a pathogen in polymicrobial infections. We evaluated the efficacy of cefozopran (CZOP) using polymicrobial pyometra rats. Rats were infected with a mixed intrauterine inoculation of E. faecalis plus either Bacteroides fragilis or Prevotella bivia (minimal inhibitory concentration of CZOP; E. faecalis: 6.25 µg/ml, B. fragilis: 12.5 µg/ml, P. bivia: 12.5 µg/ml). Immediately after inoculating 105 CFU of each organism/rat, CZOP (either 40 mg/kg, i.v., q.i.d., for 5 days or 80 mg/kg, i.v., b.i.d., for 5 days) was administered. The intrauterine inflammatory change and bacterial counts in the CZOP-treated group were compared with those in the nontreated control group. CZOP significantly (p < 0.01) decreased the bacterial counts except for B. fragilis in the regimen of 80 mg/kg b.i.d. However, the 40 mg/kg, q.i.d., regimen significantly (p < 0.05) reduced bacterial counts compared to 80 mg/kg, b.i.d. These results suggest that CZOP in a more divided dose is efficacious for the treatment of polymicrobial infections associated with E. faecalis in pyometra.
In vitro Bactericidal Activitiesand Morphologic Changes in Escherichia coli and Bacteroides fragilis by Cephalosporins
Authors: Mikamo Hiroshige , Kawazoe Kyoko , Sato Yasumasa , Hayasaki You , Satoh Masaru , Kai Jyunko , Tamaya Teruhiko
Published: April 2003

Polymicrobial infections with aerobes and anaerobes are common in pelvic inflammatory diseases. New parenteral cephalosporins have been widely used against those infections. We investigated in vitro morphologic changes and bactericidal activities on Escherichia coli and Bacteroides fragilis by cephalosporins; cefluprenam (CFLP), ceftazidime (CAZ) or cefotaxime (CTX). CFLP induced morphologic changes (filamentation) and bactericidal activities on E. coli and B. fragilis. Morphologic changes were observed by electron microscope. The filamentation induced by CFLP was time and concentration dependent. The bactericidal activity of CFLP against E. coli was almost equal to those of CAZ and CTX. The bactericidal activity of CTX against B. fragilis was superior to those of CFLP and CAZ. These results suggest that there are characteristic aspects in each cephalosporin.
Effect of Zidovudine Therapy in Patients with HIV Infection on Endogenous Interferon Plasma Levels and the Hepatic Cytochrome P450 Enzyme System
Authors: Brockmeyer N.H. , Barthel B. , Mertins L. , Goos M.
Published: April 2003

In this study, we wanted to investigate if there are differences in endogenous interferon (IFN) plasma levels in patients with different stages of HIV infections before and after therapy with zidovudine (ZDV) and determined the influence of ZDV therapy on the hepatic monooxygenase system by measuring the antipyrine pharmacokinetics. Therefore we investigated the endogenous IFN plasma levels in patients with asymptomatic HIV infection (CDC/WHO A1, n = 10) and patients with AIDS (CDC/WHO C3, n = 10). In AIDS plasma IFN-α and IFN-γ levels are elevated (15.6 ± 5.8 U/ml; 2.1 ± 0.7 U/ml) compared to patients with an asymptomatic HIV infection (6.1 ± 3.3 U/ml; 0.6 ± 0.3 U/ml). The antipyrine clearance was significantly reduced in the group of AIDS patients (43.1 ± 7.2 ml/min compared to 56.4 ± 8.7 ml/min). In a second study with 11 patients in stage CDC/WHO A1/2 and CDC/WHO B/C3 each, we studied the effect of a 14-day administration of ZDV on the endogenous plasma IFN levels and the CYP450 enzyme activity using the antipyrine pharmacokinetics as a parameter. We investigated the antipyrine clearance, clearance to metabolite and half-life by using HPLC. IFNs were measured by RIA or ELISA, respectively. In the first group no significant alterations of antipyrine kinetics or plasma IFN levels were observed after treatment with ZDV. In contrast to these results, we found a significant decrease in IFN-α and IFN-γ (19.8 ± 3.6 U/ml, 4.6 ± 1.5 U/ml before; 7.9 ± 2.6 U/ml, 1.9 ± 1.3 U/ml after administration of ZDV), a decrease in antipyrine half-life, an elevation of the antipyrine clearance (49.8 ± 15.7 ml/min, 57.3 ± 13.7 ml/min) and an elevation of the clearances to metabolite.
In vitro and in vivo Antibacterial Activities of AM-1155 in the Fields of Obstetrics and Gynecology
Authors: Mikamo Hiroshige , Kawazoe Kyoko , Sato Yasumasa , Hayasaki Yoh , Izumi Koji , Tamaya Teruhiko
Published: April 2003

AM-1155 is a new 8-methoxyquinolonecarboxylic acid with a broad spectrum of antibacterial activity. It inhibited more than 90% of clinical isolates of Streptococcus agalactiae, Escherichia coli, Peptostreptococcus magnus, Bacteroides fragilis and Prevotella bivia at the concentration of 3.13 mg/l. The antibacterial activity of AM-1155 was almost equal to that of sparfloxacin. The in vivo efficacy of AM-1155 was evaluated using a polymicrobial pyometra (E. coli and B. fragilis) model of rats. The accumulation of neutrophils to the uterus in the AM-1155-treated group was less marked than that of the nontreated group, as well as the bacteriological response. These results suggest that the new antimicrobial agent AM-1155 might be useful for the treatment of polymicrobial infections in the fields of obstetrics and gynecology.
Therapeutic Efficacy of Cefozopran in a Murine Model of Haematogenous Pneumococcal Meningitis
Authors: Iizawa Y. , Hiroe K. , Nakao M. , Okonogi K.
Published: April 2003

Antimicrobial regimens for the treatment of pneumococcal meningitis are not established. We have produced a murine model of haematogenous pneumococcal meningitis and have examined its usefulness for determining the required dosage and term of antimicrobial agents. Streptococcus pneumoniae serotype 6 was injected intraperitoneally (inoculum: about 1 × 104 CFU) into mice. Although half of the mice died within 2 days, the surviving mice showed positive bacterial cultures, increase of the protein level, decrease of the glucose level and infiltration of polymorphonuclear leucocytes into cerebrospinal fluids (CSF). When cefozopran was administered subcutaneously twice a day for 1–3 days starting 2 days after infection, dose- and duration-dependent effects were observed and all mice treated with 20 mg/kg of cefozopran for 3 days survived. The penetration rate of cefozopran from blood to CSF in infected mice was 44.7%, which was 6 times higher than that obtained in uninfected mice. This model may be useful for investigating the pathogenesis of haematogenous pneumococcal meningitis and its therapy.
Effect of Different β-Lactams in Combination with β-Lactamase Inhibitors in the Presence or Absenceof Tobramycin against Some Enterobact eriaceae Producing Extended-Spectrum β-Lactamases
Authors: Ferrara Anna , Dos Santos Conceicão , Cimbro Monica
Published: April 2003

Extended-spectrum β-lactamase (ESBL) production among members of the family Enterobacteriaceae generally involves resistance to oxyimino-cephalosporins and monobactams, while implying different susceptibility profiles with other antimicrobial agents. We have investigated the activity of some β-lactam antibiotics, alone or in double and triple combinations with β-lactamase inhibitors, in the presence or absence of tobramycin (TOB), against some Enterobacteriaceae producing ESBL by means of time-kill curves. Antimicrobials employed were ceftazidime (CAZ), cefotaxime (CTX), TOB, ampicillin (AMP), ampicillin-sulbactam (ASL), amoxicillin (AML), amoxicillin-clavulanic acid (AMC), piperacillin (PIP) and piperacillin-tazobactam (TZP), at 1/4 minimum inhibitory concentration for susceptible strains and at achievable serum concentrations for resistant strains. Only the combinations CTX-ASL, CAZ-ASL and PIP-ASL were synergistic, both at 6 and 24 h, on some strains of Klebsiella species.
In vitro Activities of E1101, a Novel Oral Cephalosporin, against Bacteria Causing Infections in Obstetric and Gynecological Patients
Authors: Mikamo Hiroshige , Sato Yasumasa , Hayasaki Yoh , Kawazoe Kyoko , Tamaya Teruhiko
Published: April 2003

E1101 is a new oral cephalosporin with a broad spectrum of antibacterial activity. It inhibited more than 90% of clinical isolates of Streptococcus agalactiae, Escherichia coli and Peptostreptococcus magnus at the concentration of 3.13 mg/l. E1101 was the most active agent against S. agalactiae and E. coli. Since none of the compounds was sufficiently active against the Bacteroides fragilis and Prevotella bivia isolates, they are not appropriate in the treatment of patients with infections caused by these organisms. The results of this study suggest that, subject to confirmation by clinical trials, E1101, in combination with an agent with reliable activity against anaerobic bacteria, is suitable as empirical therapy of patients with obstetric and gynecological infections.
Effect of a 17-Member Azalide on Tumor Cell Growth
Authors: Grdiša Mira , Lopotar Nevenka , Pavelić Krešimir
Published: April 2003

The action of the 17-member azalide 4′-demycarosyl-20-deoxo-20-(di-N-benzylamino)-8a-aza-8a-homotylosin was examined in vitro using five different human cell lines: laryngeal carcinoma (Hep2), pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), neuroblastoma, and normal diploid fibroblast (Hef522). After exposure, the cell growth was arrested, and morphological changes occurred in a dose-dependent manner. At a concentration of 10–4 M the azalide completely inhibited the growth of all cell lines examined and induced morphological changes such as cell shrinkage, chromatin condensation, and DNA fragmentation. These features point to apoptosis.
Antimicrobial Prophylaxis in Laparoscopic and Conventional Cholecystectomy
Authors: Lippert H. , Gastinger J.
Published: April 2003

Background: Postoperative infection following cholecystectomy poses a significant threat to recovery, with major cost repercussions. Though antimicrobial prophylaxis is commonly practiced, its value – particularly in laparoscopic cholecystectomy – has not yet been adequately documented. Method: In a prospective multicenter quality assurance study in 28 German hospitals, an analysis of data collected on 4,477 patients undergoing conventional (n = 1,349) or laparoscopic (n = 3,128) cholecystectomy was performed; 2,217 patients received and 2,260 did not obtain perioperative antibiotic cover. Results: Postoperative infections occurred in a total of 136 patients, with infection rates of 5.0% in those without prophylaxis, 0.8% in those on ceftriaxone, and 1.2% in those on other antibiotic regimens. Patients receiving prophylaxis fared significantly better than those with no prophylaxis in terms of the rate of postoperative wound infections, chest infections, other complications, reoperation and mortality. Conclusion: Neither laparoscopic nor conventional open cholecystectomy should be performed without adequate perioperative antimicrobial prophylaxis in future, especially since such measures also reduce hospital stay and hence the costs.
Comparative Activity of Piperacillin/Tazobactam against Clinical Isolates of Extended- Spectrum β-Lactamase-Producing Enterobacteriaceae
Authors: Pagani Laura , Migliavacca Roberta , Luzzaro Francesco , Giacobone Ernesto , Perilli Mariagrazia , Micheletti Piero , Amicosante Gianfranco
Published: April 2003

β-Lactam resistance on the part of the Enterobacteriaceae causes serious therapeutic problems in our institutions due to their production of extended-spectrum β-lactamases (ESβLs). We studied the in vitro activity of β-lactam/β-lactamase inhibitor combinations and third-generation cephalosporins and monobactams against 71 clinically relevant Enterobacteriaceae which produced TEM- and SHV-derivative ESβLs. Of the single drugs and combinations tested, piperacillin/tazobactam proved to be the most effective. Piperacillin/tazobactam was highly active against Proteus mirabilis, with minimum inhibitory concentrations (MICs) ranging from 0.125 to 16 µg/ml; Escherichia coli (MICs from 2 to 16 µg/ml) and Serratia marcescens (MICs from 4 to 8 µg/ml), while its activity against Klebsiella pneumoniae ESβL producers turned out to be closely related to the type and the amount of enzyme produced, the MIC ranging from 1 to 128 µg/ml. The antibacterial activity of piperacillin/tazobactam was stronger than that of ticarcillin/clavulanate, ceftriaxone, cefotaxime, ceftazidime and aztreonam, and the combination shared favorable in vitro activity properties against the ESβL producers with imipenem which, however, should be kept as reserve product.
Inhibition of Malaria-Infected Erythrocytes by Deoxyspergualin: Effect on in vitro Growth of Malarial Cultures
Authors: Midorikawa Yutaka , Haque Quazi Manjurul , Nakazawa Shusuke
Published: April 2003

The effect of deoxyspergualin (DSG) on the K1 strain of human malarial parasite Plasmodium falciparum in vitro was studied to test a possible new antimalarial chemotherapy. Hypoxanthine labeled with tritium (3H) was used to assess macromolecular synthesis. The inhibitory effects of DSG on the parasite peaked after 72 h of incubation. Parasitemia without DSG treatment was 9%, whereas at a DSG concentration of more than 156 µg/ml it was less than 1%. The amount of [3H]hypoxanthine taken up decreased with increasing DSG concentration. DNA synthesis of malarial activity decreased with increasing DSG concentration. These findings provide more evidence for the effects of DSG on this malarial parasite. As in previous in vivo studies done with DSG, the in vitro findings showed that DSG may be a new antimalarial drug.
Role of Inhibition of Penicillin Binding Proteins and Cell Wall Cross-Linking by Beta-Lactam Antibiotics in Low- and High-Level Methicillin Resistance of Staphylococcus aureus
Authors: Higashi Yasuyuki , Wakabayashi Akiko , Matsumoto Yoshimi , Watanabe Yuji , Ohno Akira
Published: April 2003

We have investigated the relationships between the minimum inhibitory concentrations (MICs) of eight β-lactams and their binding affinities of penicillin binding proteins in low- and high-level methicillin-resistant Staphylococcus aureus (MRSA). For high-level MRSA (H-MRSA), a significant correlation was found between IC50 for PBP2A and MIC, whilst no clear relationship was apparent for low-level MRSA (L-MRSA). However, the product of the IC50s for PBP2A and PBP4 significantly correlated with the MIC in L-MRSA. Since PBP4 is thought to mediate secondary cross-linking of the staphylococcal cell wall, we analyzed the effect on cell wall cross-linking of L- and H-MRSA of two representative drugs (cefoselis and flomoxef). Interestingly, the decrease in cell wall cross-linking, which was clearly observed in L-MRSA, was diminished with H-MRSA. It is concluded that for L-MRSA, a reduction in cell wall cross-linking caused by inhibiton of PBP4 may contribute to the antimicrobial activity of β-lactam antibiotics, while for H-MRSA, inhibition of PBP2A mainly determines the antimicrobial activity. Since neither alteration of expression nor binding affinity of PBP4 were observed in these studies, unknown factors must operate to diminish the effect of PBP4 inhibition and contribute to the mechanism of high level resistance of MRSA.
In vitro Activities of Pazufloxacin,a Novel In jectable Quinolone, against Bacteria Causing Infections in Obstetric and Gynecological Patients
Authors: Mikamo Hiroshige , Sato Yasumasa , Hayasaki Yoh , Kawazoe Kyoko , Tamaya Teruhiko
Published: April 2003

T-3762 is an injectable new quinolone with a broad spectrum of antibacterial activity. Pazufloxacin (T-3761) is an active form of T-3762. The minimal inhibitory concentrations (MICs) of pazufloxacin for 50% of the clinical isolates tested were 3.13 µg/ml for Streptococcus agalactiae, 6.25 µg/ml for Gardnerella vaginalis, 0.025 µg/ml for Escherichia coli, 0.78 µg/ml for Pseudomonas aeruginosa, 6.25 µg/ml for Peptostreptococcus magnus, 6.25 µg/ml for Bacteroides fragilis and 12.5 µg/ml for Prevotella bivia. The MICs of T-3762 for 90% of the clinical isolates tested were 3.13 µg/ml for S. agalactiae, 6.25 µg/ml for G. vaginalis, 0.10 µg/ml for E. coli, 12.5 µg/ml for P. aeruginosa, 25 µg/ml for P. magnus, 12.5 µg/ml for B. fragilis and 25 µg/ml for P. bivia. The results of this study suggest that, subject to confirmation by clinical trials, T-3762, in combination with an agent with reliable activity against anaerobic bacteria, is suitable as an empirical therapy of patients with obstetric and gynecological infections.
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 Escherichia coli with these neutrophilic functions after pretreatment with various sub-MICs of cefodizime. E. coli 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.
Synthesis and Screening for Anti-HIV Activity of Some N-Mannich Bases of Isatin Derivatives
Authors: Pandeya S.N. , Yogeeswari P. , Sriram D. , de Clercq E. , Pannecouque C. , Witvrouw M.
Published: April 2003

The effect of about 12 new compounds of Mannich bases of isatin against HIV-1 (IIIB) and HIV-2 (ROD) strains in MT 4 cells was studied. The screening method employed was MTT. In initial studies, one compound has shown maximum protection of 16% in subtoxic concentration.
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

Background: 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). Methods: 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/m2) and etoposide (80 mg/m2) 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. Results: 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). Conclusion: Intrapleural administration of CDDP and etoposide was an effective and acceptable regimen for patients with MPE due to NSCLC.
Postprostatectomy Orchitis: Reduction in Incidence Using Perioperative Ceftriaxone and Postoperative Ciprofloxacin
Authors: Anyanwu Stanley N.C.
Published: April 2003

Postoperative orchitis increases the morbidity and overall hospital stay after prostatectomy. A retrospective review of our initial series of 174 cases revealed an incidence of 6% which is similar to other studies. We reviewed our bacterial flora and antibiogram and subsequently started a prospective study combining peri-operative ceftriaxone and postoperative ciprofloxacin, which we compared to our previous series where we used perioperative ceftriaxone followed by postoperative gentamicin and ampicillin. There was an abolition of orchitis as a consequence and a significant reduction in the rate of wound infection. We conclude that a combination of ceftriaxone and ciprofloxacin is efficacious in reducing the rate of infective complications following prostatectomy. We recommend the use of these or similar drugs based on local microbial flora.
In vitro Bactericidal Activities of a New Oral Cephalosporin, E1100, and Morphologic Changes on Escherichia coli
Authors: Mikamo Hiroshige , Satoh Masaru , Kai Jyunko , Sato Yasumasa , Hayasaki Yoh , Tamaya Teruhiko
Published: April 2003

Escherichia coli 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 E. coli 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 E. coli. The filamentation induced by E1100 was time and concentration dependent.
Apoptosis of Cultured Neuroblastoma Cells Is Induced by Ceramide and Not by Ligation of the Fas/Apo-1/CD95 Receptor
Authors: Barthlen Winfried , Schäfer Jochen , Girgert Rainer , Schuster Monika , Schweizer Paul
Published: April 2003

The expression of the Fas/APO-1/CD95 receptor on the neuroblastoma cell lines IMR-32, Kelly, SK-N-SH, LS and SiMa was investigated. The induction of apoptosis was attempted by incubation with Fas antibody IgM and IgG, Fas ligand and with ceramide. All neuroblastoma cell lines proved to be positive for Fas/APO-1/CD95 receptor expression by FACS. However, propidium iodide staining in FACS showed that neither incubation with the Fas antibody nor with the Fas ligand resulted in convincing apoptosis of the neuroblastoma cells. On the other hand, incubation with ceramide rapidly led to all signs of apoptosis morphologically and in the FACS. Therefore, other pathways than Fas/Apo-1/CD95 ligation must be of significance for the apoptosis of these neuroblastoma cell lines.
Nitazoxanide, a Nitrothiazolide Antiparasitic Drug, Is an Anti-Helicobacter pylori 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 Helicobacter pylori. The MIC90 of both NTZ and TIZ against 37 clinical isolates was 8 μg/ml. Vacuolating toxin activity of H. pylori assayed by HeLa cell vacuole formation was inhibited by NTZ at a sub-MIC. In contrast, urease production by H. pylori 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 H. pylori, even when the bacteria are resistant to MTZ.
Susceptibility Surveillance among Gram-Negative Bacilli at a Cancer Center
Authors: Jacobson Kalen , Rolston Kenneth , Elting Linda , LeBlanc Barbara , Whimbey Estella , Ho Dah Hsi
Published: April 2003

We conducted a survey of susceptibility among 758 gram-negative bacilli (GNB; collected from cancer patients over a 3-month period) to commonly used antibiotics. The overall resistance among GNB was least for piperacillin/tazobactam and meropenem (5 and 6%, respectively) followed by cefepime (8%), imipenem (9%), amikacin (12%), ofloxacin (13%), ciprofloxacin, ceftazidime and ticarcillin/clavulanate (14% each), aztreonam (18%) and tobramycin (24%). In comparison to data on antibiotic resistance to ceftazidime, imipenem, ciprofloxacin and aztreonam in similar studies in 1985 and 1994, resistance has significantly increased to all four antibiotic classes. Based on our current study, meropenem, cefepime, imipenem and piperacillin/tazobactam would be the most appropriate choices in our institution for empiric therapy of GNB infections in febrile neutropenic patients.
‘Subinhibitory’ Erythromycin Represses Production of Pseudomonas aeruginosa Lectins, Autoinducer and Virulence Factors
Authors: Sofer Danit , Gilboa-Garber Nechama , Belz Aviva , Garber Nachman Chaim
Published: April 2003

Pseudomonas aeruginosa infection is preceded by selective adhesion of the bacteria to the host target cells via diverse adhesins, including lectins. This step enables maximal damage to the target host cells by the bacterially secreted injurious toxins and enzymes. The production of both lectins and many of the virulence factors is positively controlled by transcription activators including signaling autoinducers (N-acyl-L-homoserine lactones). We show in this communication that erythromycin at subminimal growth inhibitory concentrations simultaneously suppresses the production of P. aeruginosa hemagglutinins (including lectins), protease, hemolysin and homoserine lactone autoinducers. The antibiotic-treated bacteria also show reduced virulence to mice, endorsing clinical observations that indicate the efficiency of low-dose erythromycin treatment of persistent drug-resistant P. aeruginosa infections.
In vitro Bactericidal Activities of Antimicrobial Agents and Morphologic Changes on Prevotella bivia
Authors: Mikamo Hiroshige , Sato Yasumasa , Hayasaki Yoh , Kawazoe Kyoko , Izumi Koji , Satoh Masaru , Kai Jyunko , Tamaya Teruhiko
Published: April 2003

Prevotella bivia is common in pelvic inflammatory diseases. Parenteral antimicrobial agents have been widely used against those infections. We investigated the bactericidal activities of three cephalosporins, i.e. cefluprenam (CFLP), ceftazidime (CAZ) and cefotaxime (CTX) and of two other antimicrobial agents, i.e. clindamycin (CLDM) and imipenem (IPM) against P. bivia. We also investigated the in vitro morphological changes induced by these agents in P. bivia. Cephalosporins exhibited bactericidal activities against P. bivia and induced time- and concentration-dependent morphological changes in P. bivia (filamentation). CLDM and IPM also had bactericidal activities, but induced different morphologic alterations: formation of spheroblasts and lysis. These results confirm the fact that each antimicrobial agent has characteristic aspects.
Ceftriaxone plus Once Daily Aminoglycoside with Filgrastim for Treatment of Febrile Neutropenia: Early Hospital Discharge vs. Standard In-Patient Care
Authors: Rapoport B.L. , Sussmann O. , Herrera M.V. , Schlaeffer F. , Otero J.C. , Pavlovsky S. , Iglesias L. , Stein G. , Charnas R. , Heitlinger E. , Handschin J.
Published: April 2003

Background: In febrile neutropenic patients, ceftriaxone plus an aminoglycoside is effective for the treatment of infection, while filgrastim reduces the extent and duration of neutropenia. Because the once daily dosing regimen of this combination permits ambulatory treatment, there is a need to test criteria for early hospital discharge. Methods: Hospitalized adult patients with febrile neutropenia (following chemotherapy) considered to be potentially treatable on a follow-up out-patient basis were entered into this open-label, multinational study. Patients received a once daily combination of ceftriaxone for ≥5 days, aminoglycoside for ≥2 days, and filgrastim until the absolute neutrophil count was ≥1.0 × 109/l for 2 days. Those initially responding to therapy (reduction of fever by ≥1°C within 72 h, and clinical improvement) were randomized into standard in-patient or follow-up out-patient treatment groups, the latter patients being discharged from hospital early, after meeting defined criteria. Results: 105 patients were enrolled, of whom 21 initial non-responders were not randomized. Efficacy was evaluable in 80 patients. Success (resolution of fever and symptoms, maintained for 7 days after cessation of therapy, and eradication of infecting pathogens) was similar among in-patients (40/42, 95%) and out-patients (34/38, 89%). The duration of hospitalization was shorter for out-patients than in-patients (median of 4 vs. 6 days, respectively). No hospital readmissions were necessary in out-patients. All other efficacy parameters assessed were comparable in both groups, as was tolerability/safety. One potentially drug-related death was reported. Conclusions: Patients who satisfy prospectively defined criteria for early discharge can be treated safely on an out-patient basis with a regimen of once daily ceftriaxone plus an aminoglycoside with filgrastim. In addition to reducing healthcare costs, it may improve patients’ quality of life.
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(0–24)) or the trough plasma concentration (C24) after co-administration with either gemifloxacin or placebo. Geometric means for AUC(0–24) 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(0–24) 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 (Cmax) 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.