bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Experience with a Decision Support Computer Program Using Bayes’ Theorem to Diagnose Chest Pain Patients
Authors: Aase Ottar
Published: April 2003

A decision support computer program (DSP) was used by the emergency room physician as a diagnostic tool on patients admitted with acute chest pain to guide the referral of these patients either to the Coronary Care Unit (CCU) or general ward. The DSP used Bayes’ theorem on 38 anamnestic and clinical variables to classify patients into one of nine diagnoses. During a six months trial period 32 physicians used the DSP to diagnose 493 patients admitted with acute chest pain. The physicians referred the patients to CCU or general ward based on their clinical judgements, the ECG findings and the diagnostic estimates given by the DSP. The program correctly diagnosed 150 (84%) of 178 patients with acute myocardial infarction and 63 of 112 patients with unstable angina. However, acute ischemic heart disease (acute myocardial infarction or unstable angina) was correctly classified by the DSP for 259 (89%) of 290 patients. By using the DSP, the number of patients unnecessarily referred to CCU was reduced from 35% to 19% and the number of patients in need of CCU observation misallocated to general ward was reduced from 13% to 10%. Thus, use of the DSP in the emergency room on easily available anamnestic and clinical variables may improve referrals to the CCU, optimize therapy and resource use.
Hemodynamic Abnormalities in the Left Atrial Appendage in Patients with Paroxysmal Atrial Fibrillation, with Special Reference to Albumin-Contrast Echocardiographic Aspects
Authors: Kato Hiroshi , Yoshida Masahiro , Takata Kotaro , Kanehara Hideo , Maekawa Naomi , Ohnishi Teiji , Murakita Hajime , Kuriyama Toyoko , Yamamoto Makoto
Published: April 2003

Aim: We assessed the prolonged dysfunction of the left atrial appendage caused by paroxysmal atrial fibrillation. Methods and Results: Transesophageal echocardiography with intravenous albumin-microspheres (Albunex, 0.2 ml/kg) was performed in 100 consecutive patients (44 patients in sinus rhythm without previous paroxysmal atrial fibrillation: 13 patients in sinus rhythm who had had previous episodes of paroxysmal atrial fibrillation; and 43 patients with sustained atrial fibrillation). We compared the left atrial appendage ejection fraction and degree of opacification in the left atrial appendage with Albunex in the groups. Patients with previous paroxysmal atrial fibrillation had lower left atrial appendage ejection fractions than patients in sinus rhythm without paroxysmal atrial fibrillation (33 ± 14 vs. 47 ± 14%, p < 0.001). More than half of the patients (7/13 [54%]) with previous paroxysmal atrial fibrillation showed delayed and incomplete opacification of the left atrial appendage with Albunex. Conclusion: We conclude that paroxysmal atrial fibrillation causes left atrial appendage stunning, at least in some patients.
Attenuated Responses of Doppler-Derived Hemodynamic Parameters during Supine Bicycle Exercise in Heart Transplant Recipients
Authors: Auerbach Ilan , Tenenbaum Alexander , Motro Michael , Stroh Chaim I. , Har-Zahav Yedael , Fisman Enrique Z.
Published: April 2003

The aim of this study was to characterize Doppler-derived hemodynamic parameters in heart transplant recipients at rest and during symptom-limited supine bicycle exercise. Eighteen sedentary patients aged 54.0 ± 2 years, 1.6 ± 1.0 years following cardiac transplantation, and 18 sedentary healthy volunteers aged 51.8 ± 4 years were investigated. Basic hemodynamic parameters and Doppler-derived parameters were recorded at rest and at peak dynamic exercise. Resting heart rate, blood pressure and rate-pressure product were higher in the transplanted patients (p < 0.001). However, in comparison with the resting state, the increase in these parameters at exercise was lower in heart transplant recipients. In the healthy, dynamic exercise induced an increase in peak flow velocity, mean acceleration, flow velocity integral, stroke volume, cardiac output and cardiac index (p < 0.001 for all) while systemic vascular resistance, ejection time and acceleration time decreased (p < 0.001 for all). The following parameters increased in the transplanted patients at dynamic exercise: peak flow velocity, cardiac output and cardiac index (p < 0.001), mean acceleration (p < 0.01) and flow velocity integral (p < 0.05). Ejection time decreased (p < 0.05) and acceleration time and systemic vascular resistance remained unchanged. In conclusion, at rest peak flow velocity, mean acceleration, flow velocity integral and stroke volume are lower in the transplanted than in the healthy controls, while cardiac output, cardiac index and systemic vascular resistance are equal. Our study demonstrates attenuated responses of basic hemodynamic parameters and Doppler-derived cardiovascular indices at symptom-limited supine bicycle exercise in heart transplant recipients compared to healthy volunteers.
Changes in the mRNA Levels of Delayed Rectifier Potassium Channels in Human Atrial Fibrillation
Authors: Lai Ling-Ping , Su Ming-Jai , Lin Jiunn-Lee , Lin Fang-Yue , Tsai Chang-Her , Chen Yih-Sharng , Tseng Yung-Zu , Lien Wen-Pin , Huang Shoei K. Stephen
Published: April 2003

Introduction: We measured mRNA levels of delayed rectifier potassium channels in human atrial tissue to investigate the mechanism of the shortening of the atrial effective refractory period and the loss of rate-adaptive shortening of the atrial effective refractory period in human atrial fibrillation. Methods and Results: A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The mRNA amounts of KVLQT1 (IKs), minK (β-subunit of IKs), HERG (IKr), and KV1.5 (IKur) were measured by reverse transcription-polymerase chain reaction and normalized to the mRNA amount of GAPDH. We found that the mRNA levels of KV1.5, HERG and KVLQT1 were all significantly decreased in patients with persistent atrial fibrillation for more than 3 months. In contrast, the mRNA level of minK was significantly increased in patients with persistent atrial fibrillation for more than 3 months. We further showed that these changes were independent of the underlying cardiac disease, atrial filling pressure, gender and age. We also found that there was no spatial dispersion of mRNA levels among the four atrial sampling sites. Conclusions: Because the decrease in potassium currents results in a prolonged action potential, the shortening of the atrial effective refractory period in atrial fibrillation should be attributed to other factors. However, the decrease in IKs might contribute, at least in part, to the loss of rate-adaptive shortening of the atrial refractory period.
Visual versus Computerized Analysis of Upsloping ST Segment Depression in the Exercise Electrocardiogram
Authors: Walamies Markku A. , Kööbi Tiit , Hämäläinen Liisa I. , Ahonen Esa A.
Published: April 2003

A slowly upsloping ST segment depression is an abnormal, and a rapidly upsloping ST segment depression is a normal exercise ECG response. We investigated the agreement of expert physicians on the visual classification of the ST segment depression, and compared the (majority) vote with the computer-generated ST slope. A total of 206 exercise ECG leads with an amplitude of the ST segment depression ≥0.15 mV and a ST segment slope ≥0.5 mVs–1 were evaluated. All three interpreters agreed in 68 cases, two agreed in 123 cases, and all disagreed in 15 cases. Intraobserver agreement was 61%. The ST segment slope was significantly (p < 0.001) greater in leads generally interpreted as rapidly upsloping (n = 38; 2.1 ± 0.8 mVs–1), than in those interpreted as slowly upsloping (n 121; 1.3 ± 0.6 mVs–1) or horizontal (n = 32; 1.1 ± 0.4 mVs–1), although there was some overlap. Thus, standardization of the computer-assisted exercise ECG interpretation should be continued.
Soluble VCAM-1 and E-Selectin, but Not ICAM-1 Discriminate Endothelial Injury in Patients with Documented Coronary Artery Disease
Authors: Semaan Husam B. , Gurbel Paul A. , Anderson Jeffrey L. , Muhlestein Joseph B. , Carlquist John F. , Horne Benjamin D. , Serebruany Victor L.
Published: April 2003

It has been shown that endothelial cell adhesion molecules play an important role in the development of coronary atherosclerosis and inflammatory disease. We sought to test whether soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin are increased in patients with documented coronary artery disease (CAD). Plasma levels of VCAM-1, ICAM-1 and E-selectin were measured in 40 patients with documented CAD, 20 subjects with angiographically documented normal coronary arteries, and 14 healthy volunteers. Patients with documented CAD exhibited significant elevation of VCAM-1 (535 ± 227.1 ng/ml, p = 0.0001), E-selectin (69.4 ± 29.4 ng/ml, p = 0.006), but not ICAM-1 (320.5 ± 65.1 ng/ml, p = 0.9) concentrations as compared to subjects with normal coronary arteries (252.3 ± 79.8, 49.7 ± 22.0 and 311.4 ± 40.2 ng/ml), and healthy controls (110.0 ± 17.7, 29.0 ± 2.0 and 237.5 ± 46.5 ng/ml), respectively. Soluble markers of endothelial injury are not uniformly increased in patients with documented CAD as compared to those with normal coronary arteries and healthy controls. However, VCAM-1 and E-selectin, but not ICAM-1 could identify endothelial injury in such patients.
Using Internal Jugular Pulsations as a Manometer for Right Atrial Pressure Measurements
Authors: Constant Jules
Published: April 2003

External jugulars are not reliable as an indication of right atrial pressure because of their passage through two right angles and also because they are often not visible. The top level of internal jugular pulsations which are transmitted to the skin of the neck serves as a pulsation manometer. A standard chest angle of 45° and a standard zero at the sternal angle can be used together with a centimeter ruler to give a useful measurement of jugular venous pressure. The use of a carpenter level (spirit level) and a round-bottomed tongue blade measured off in centimeters will allow accurate follow-up. An increase in tone-volume can be detected by the abdominal compression test or abdominojugular test (also known by the outdated terminology of hepatojugular reflux).
Preoperative Predictors of Late Postoperative Outcome among Patients with Nonischemic Mitral Regurgitation with 'High Risk' Descriptors and Comparison with Unoperated Patients
Authors: Wencker Detlef , Borer Jeffrey S. , Hochreiter Clare , Devereux Richard B. , Roman Mary J. , Kligfield Paul , Supino Phyllis , Krieger Karl , Isom O. Wayne
Published: April 2003

Among patients with chronic nonischemic mitral regurgitation (MR), high short-term mortality risk can be identified by left (LV) and/or right ventricular (RV) ejection fraction (EF) criteria (LVEF ≤45% and/or RVEF ≤30%). Mitral valve replacement or repair (MVR) significantly improves outcome in this subgroup, but predictors of late postoperative survival are not known, and the benefit of MVR has not been defined in patients matched for severity of LV and RV dysfunction. Therefore, prospective assessment of 14 consecutive high risk MR patients was performed before MVR and during 9 years (average) postoperatively to define echocardiographic and radionuclide angiographic predictors of survival; survival also was evaluated in a contemporaneous series of 9 high risk unoperated MR patients, and in subgroups of operated and unoperated patients matched for EF. Of 14 MVR patients, 4 died (3 cardiac: 1 sudden, 2 congestive heart failure). Only preoperative RVEF ≤20% significantly predicted postoperative deaths (rest p = 0.032; exercise p = 0.05). Of 9 unoperated patients, 8 died. Mortality risk of unoperated patients remained higher than that of MVR patients when groups were matched for preoperative LVEF (p = 0.0001). Among patients with RVEF >20%, MVR significantly improved survival versus medical treatment (rest: p < 0.0001, exercise: p = 0.0003). In high risk MR patients, MVR improves survival; preoperative RV performance can define subgroups with different long-term postoperative survival.
Amyotrophic Lateral Sclerosis with a ‘Pseudo-Infarction’ Pattern on the Electrocardiograph
Authors: Li Ai-Hsien , Hsu Kwan-Lih , Liau Chiau-Suong , Tseng Yung-Zu , Lee Yuan-Teh
Published: April 2003

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease involving both the upper and lower motor neurons in the brain stem and spinal cord. Although it is well known that various central nervous system disorders can produce a ‘pseudo-infarction’ pattern on the electrocardiogram, there have been no reports of this particular pattern in ALS patients. This report concerns an ALS patient who presented with an ECG pattern of S–T elevation followed by biphasic T and inverted T without any detectable myocardial abnormality. Data from the present case suggest that this pattern may be an inherent characteristic of ALS.
Hemodynamic and Hormonal Effects of the Angiotensin II Antagonist, Candesartan Cilexetil, in Patients with Congestive Heart Failure
Authors: Yoshimura Michihiro , Yasue Hirofumi
Published: April 2003

Candesartan cilexetil is a newly synthesized, specific angiotensin II type 1 receptor antagonist. Candesartan cilexetil is a prodrug, and is converted to its active form, candesartan, by the enzyme esterase at the time of intestinal absorption. We conducted a single-dose study to evaluate the effect of candesartan cilexetil on cardiac hemodynamics and hormone response in 13 patients with congestive heart failure. Mean blood pressure did not show any significant change in the patients receiving either 2 or 8 mg. Pulmonary capillary wedge pressure was reduced by 34.9% in the patients given 8 mg of candesartan cilexetil. The cardiac index did not show any significant changes. Total peripheral vascular resistance was reduced in the patients receiving 2 or 8 mg from 1 h after administration, and the tendency to decrease continued until 8 h after administration. Plasma atrial natriuretic peptide levels were reduced by 15.5% 2 h after dosing with 8 mg of candesartan cilexetil. Plasma brain natriuretic peptide levels decreased slightly after dosing with candesartan cilexetil. Administration of candesartan cilexetil reduces cardiac preload and afterload and is expected to be useful for the treatment of congestive heart failure.
Update on the Management of Acute Coronary Syndromes
Authors: Cohen Marc
Published: April 2003

At present there is debate as to whether an invasive or a conservative strategy should form the basis of an optimal management strategy for unstable angina/non-Q wave myocardial infarction (UA/NQMI). However, these approaches are complementary, not necessarily mutually exclusive. On the basis of current evidence, all patients should receive optimized medical therapy, with surgical interventions targeted at high-risk patients, to improve both clinical outcomes and cost effectiveness. While standard antithrombotic combinations have improved short-term outcomes, they do not fully eliminate the risk of recurrent ischemic episodes. The recent introduction of direct thrombin inhibitors, platelet fibrinogen receptor antagonists and low-molecular-weight heparins (LMWHs) has offered an opportunity to develop more aggressive antithrombotic regimens. Enoxaparin, an LMWH, has demonstrated improved efficacy compared with standard heparin in both the acute and chronic phases of UA/NQMI, without an increase in major complications caused by bleeding. Further studies are justified to investigate the potential of combined antithrombotic regimens containing enoxaparin as an alternative to heparin in conservative strategies and as adjuncts to interventional procedures. Recommendations for the management of UA/NQMI should be continually reviewed in response to the impact of novel treatment modalities.
Once versus Thrice Daily Tobramycin Alone and in Combination with Ceftazidime, Ciprofloxacin and Imipenem in an in vitro Pharmacodynamic Model
Authors: Zelenitsky Sheryl A. , Karlowsky James A. , Hoban Daryl J. , Kabani Amin , Zhanel George G.
Published: April 2003

The purpose of this study was to compare once daily (To24) and thrice daily (To8) tobramycin dosing regimens alone and in combination with ceftazidime, ciprofloxacin and imipenem against a clinical and ATCC strain of Pseudomonas aeruginosa. A one-compartment in vitro pharmacodynamic model was used to simulate bacteremic infection. Pharmacodynamic parameters, including rate of bacterial kill following the first dose or time to achieve a 99.9% reduction in bacterial counts (T99.9%)), extent of bacterial kill with subsequent doses and bacterial count at 24 h were characterized for each regimen. Compared to To8 alone, the combination regimens had a shorter T99.9% (p = 0.045) and greater extent of bacterial kill following the first dose (p = 0.045). Compared to To24 alone, the combination regimens demonstrated similar rates (p = 0.067) and extents of bacterial kill following the first dose (p = 0.32), however, produced lower bacterial counts at 24 h (p = 0.045). The various combination regimens appeared equally effective considering rate and extent of bacterial kill following the first dose and residual inocula at 24 h. Ciprofloxacin-containing regimens demonstrated the most bacterial kill with subsequent doses, however, bacterial counts at 24 h were similar to those of other combination regimens.
In vitro Activity of Enoxacin versus Ciprofloxacin, Fleroxacin, Lomefloxacin, Ofloxacin, Pefloxacin, and Rufloxacin against Uropathogens
Authors: Naber Kurt G. , Well Michaela , Hollauer Karin , Kirchbauer Daniela , Witte Wolfgang
Published: April 2003

Minimum inhibitory concentrations (MIC) of enoxacin, ciprofloxacin, fleroxacin, lomefloxacin, ofloxacin, pefloxacin and rufloxacin were determined against 400 uropathogens cultured from the urine of patients with complicated and/or hospital-acquired urinary tract infections (UTI) using an agar dilution method. The bacterial spectrum consisted of Enterobacteriaceae (34.5%), enterococci (31.5%), staphylococci (21.2%) and non-fermenting bacteria (12.8%). Enoxacin inhibited all but one strain (Enterobacter cloacae) of Enterobacteriaceae up to an MIC of 1 mg/l (MIC90 0.25 mg/l). Regarding the total bacterial spectrum, enoxacin inhibited 54.5, 59.5, 76.0 and 83.8% up to an MIC of 1, 2, 4 and 8 mg/l, respectively. If the same breakpoint of resistance for ofloxacin according to DIN 58 940 (NCCLS), i.e. MIC ≥4 mg/l (≥8 mg/l), is also taken for the other fluoroquinolones, and the 126 strains of enterococci are excluded, for which alternative agents, e.g. aminopenicillins, should be considered instead, the following resistance rates were found: ciprofloxacin and enoxacin 15.3% (15.0%), ofloxacin 17.2% (15.3%), pefloxacin 18.2% (15.3%), fleroxacin 19.3% (15.3%), lomefloxacin 19.7% (17.9%) and rufloxacin 31.8% (27.4%). According to their in vitro activity, all fluoroquinolones tested besides rufloxacin show similar rates of resistance against uropathogens and can therefore be considered good alternative agents for the treatment of complicated UTI.
Paclitaxel Is an Effective Antiproliferative Agent on the Human NCI-H295 Adrenocortical Carcinoma Cell Line
Authors: Fallo Francesco , Pilon Catia , Barzon Luisa , Pistorello Matteo , Pagotto Uberto , Altavilla Giuseppe , Boscaro Marco , Sonino Nicoletta
Published: April 2003

In view of a potential clinical use, we assessed the antiproliferative effect of paclitaxel on the human steroid-secreting NCI-H295 adrenocarcinoma cell line. By MTT, paclitaxel induced a dose-dependent inhibition of cell proliferation, with IC50 lower than blood levels of the drug achieved in patients treated for other malignancies. Cell exposure to paclitaxel for 24 h at the different IC50s produced a dose-responsive increase in DNA fragmentation, morphologically confirmed by electron microscopy. A time-dependent decrease in aldosterone, cortisol and testosterone was observed. Paclitaxel is an effective antiproliferative agent in this human adrenocortical carcinoma cell line. Apoptosis induced by the drug is involved in neoplastic cell death. A potential role of the drug in the treatment of patients with adrenocortical cancer could be considered.
In vitro and in vivo Antibacterial Activities of S-1090, a New Oral Cephalosporin, in the Fields of Obstetrics and Gynecology
Authors: Mikamo Hiroshige , Kawazoe Kyoko , Sato Yasumasa , Izumi Koji , Tamaya Teruhiko
Published: April 2003

S-1090 is a new synthetic, nonesterified, oral cephalosporin with a broad spectrum of antibacterial activity. The activities of S-1090 against the causative organisms in the fields of obstetrics and gynecology are superior to those of the currently prescribed oral cephems, cefdinir, cefpodoxime, and cefaclor. The in vivo efficacy of S-1090 was evaluated using uterine endometritis of model rats. The accumulation of neutrophils in the uterus in the S-1090-treated group was milder than that in the nontreated group, and the same was true for the bacteriological response. S-1090 is a promising oral cephalosporin antibiotic for the treatment of infections in the fields of obstetrics and gynecology.
Role of Fluconazole in the Management of AIDS-Related Cryptococcosis, according toDaily Dosing
Authors: Manfredi Roberto , Chiodo Francesco
Published: April 2003

No unanimous consent has been reached about treatment guidelines of cryptococcosis in the setting of AIDS, as well as about optimal fluconazole dosing in both initial and suppressive therapy. In order to evaluate the relationship between fluconazole dosing and clinical and microbiological outcome of AIDS-related cryptococcosis, a retrospective study was carried out on 30 consecutive patients. Among the 12 subjects treated with fluconazole doses <400 mg/day, an unfavorable course was significantly more frequent (early mortality, poor clinical and microbiological response, appearance of early relapses) compared with the 18 patients who received daily doses ≥400 mg, while no differences were observed between the two treatment groups according to known risk factors for a poor prognosis. When assessing maintenance treatment (22 evaluable cases), the 15 patients receiving oral fluconazole at doses <200 mg/day showed earlier disease relapse and mortality as opposed to the 7 individuals treated with high-dose fluconazole (≥200 mg/day), in the absence of significantly different risk factors for disease recurrence. Our experience pointed out a significant difference in clinical activity of fluconazole in AIDS-related cryptococcosis according to its daily dosing, and suggested 400 and 200 mg as the threshold daily dose for an effective initial and suppressive therapy, respectively, since the probability of treatment failure seemed greater with low-dose drug administration, after controlling data for prognostic markers of disease severity. Controlled studies are warranted, comparing high-dose fluconazole with standard regimens containing amphotericin B in the treatment of AIDS-associated cryptococcosis, and identifying the best fluconazole dosing for both acute-phase and maintenance treatment.
Prevalence of Antimicrobial Resistance in Eighty Clinical Isolates of Helicobacter pylori
Authors: Iovene M.R. , Romano M. , Pilloni A.P. , Giordano B. , Montella F. , Caliendo S. , Tufano M.A.
Published: April 2003

We studied the in vitro susceptibility of 80 Helicobacter pylori clinical isolates to several antimicrobials commonly used to treat the infection, using the Epsilometer test (E-test). We also compared E-test and disk diffusion test in determining H. pylori susceptibility to the same antibiotics. We found a high prevalence of H. pylori strains resistant to metronidazole (23.7%), whereas the prevalence of H. pylori strains resistant to clarithromycin was 10%. Also, a significant correlation was found between MICs obtained with the disk diffusion test and E-test for metronidazole and clarithromycin. In conclusion, our study confirms a high prevalence of metronidazole- or clarithromycin-resistant H. pylori strains. Also, our data suggest that the E-test is a single, reliable, and cost-effective method to assess in vitro susceptibility of H. pylori to antimicrobial agents commonly used to eradicate the infection.
Genetic Analysis of Serotype 23F Streptococcus pneumoniae Isolates from Several Countries by Penicillin-Binding Protein Gene Fingerprinting and Pulsed-Field Gel Electrophoresis
Authors: Yoshida Ryoji , Hirakata Yoichi , Kaku Mitsuo , Tomono Kazunori , Maesaki Shigefumi , Yamada Yasuaki , Kamihira Shimeru , Jacobs Michael R. , Appelbaum Peter C. , Kohno Shigeru
Published: April 2003

We characterized 21 strains of serotype 23F Streptococcus pneumoniae isolated in various countries with various levels of penicillin susceptibility by penicillin-binding protein (PBP) gene fingerprinting and pulsed-field gel electrophoresis (PFGE). Pneumococci isolated in Israel, Hungary, Bulgaria, Slovakia, Rumania, France, the United States, Spain and Japan were included. These strains were classified into 12 and 18 groups by PBP gene fingerprinting and PFGE, respectively. Some of the pneumococci isolated in Spain, the United States and France appeared to be genetically related by PFGE, showed the same PBP gene pattern and had similar antimicrobial susceptibility patterns. One penicillin-susceptible Bulgarian strain, with a similar PFGE pattern but a different fingerprinting pattern, may be an ancestral recipient strain that became transformed into the resistant variants. Rumanian and Israeli strains were also genetically related by PFGE. These results indicate the existence of widely spread but related pneumococci in the world. PBP 2X gene profiles of pneumococci with MICs of 0.25 µg/ml were different from each other and from penicillin-susceptible pneumococci (PSP). PBP 2B gene profiles of these resistant strains were identical. PBP 2B gene profiles of pneumococci (penicillin MICs ≥0.5 µg/ml) were different from PSP. PBP gene profiles may not only be useful for genetic analysis but also for presumed penicillin susceptibility.
In vitro Activities of Meropenem and Other Antimicrobial Agents against British Meningococcal Isolates
Authors: Abadi Fariborz J.R. , Yakubu Davis E. , Pennington T. Hugh
Published: April 2003

The in vitro activity of meropenem was compared with those of penicillin, ampicillin, cefuroxime, cetriaxone, cefotaxime, rifampicin, chloramphenicol, sulphadiazine and ciprofloxacin against 121 British meningococcal isolates by a microdilution method in Mueller-Hinton broth and by the E test. All meningococcal strains were susceptible to the agents except for ampicillin (88.4%), penicillin (88.4%), sulphadiazine (57.9%) and rifampicin (95%). The emergence of resistance problems among meningococcal isolates stresses the need for their constant monitoring and of the development of new agents. In this study we have shown that meropenem is highly active in vitro against Neisseria meningitidis. Recent studies have indicated that meropenem is highly active clinically and bacteriologically in the treatment of bacterial meningitis. Thus, the potentials of meropenem as meningococcal prophylactic and therapeutic agent needs to be fully evaluated.
Effect of Fluconazole on Human Polymorphonuclear Leucocyte Functions ex vivo against Candida albicans
Authors: Gürer Ümran Soyoǧul , Çevikbaş Adile , Johansson Candan , Derici Koray , Yardımcı Turay
Published: April 2003

Polymorphonuclear leucocytes (PMNs) are important components of host defence against fungi. We investigated the ex vivo effect of fluconazole on chemotaxis, adherence, superoxide anion (O–2) generation and intracellular killing of Candida albicans blastoconidia after the administration of fluconazole (300 mg per os) to healthy volunteers. With regard to chemotaxis in response to zymosan-activated serum (ZAS), as measured using an agarose gel technique, fluconazole neither increased, nor decreased the chemotaxis of PMNs. The adherence was significantly enhanced after exposure of PMNs to fluconazole under ex vivo conditions, whereas, O–2 production after stimulation of PMNs with ZAS was not affected by fluconazole. The effect of fluconazole on intracellular killing of C. albicans blastoconidia by PMNs was determined by viable colony count, after release of yeast cells from disturbed neutrophils. Fluconazole under in vitro conditions, at a therapeutic concentration, significantly increased the intracellular killing of C. albicans by PMNs at 30 min when compared with the results obtained in ex vivo experiments (p < 0.001). During 90 min of exposure, no significant difference was found between in vitro and ex vivo conditions (p > 0.05).
Nosocomial Outbreak of Cross-Infection due to Multiple-Antibiotic-Resistant Klebsiella pneumoniae: Characterization of the Strain and Antibiotic Susceptibility Studies
Authors: Traub Walter H. , Schwarze Isabel , Bauer Dierk
Published: April 2003

A multiple-antibiotic-resistant (MAR) strain of Klebsiella pneumoniae was introduced into a pediatric ward and subsequently colonized neonates of two wards with several cases of systemic infection. This strain produced an extended-spectrum β-lactamase and was resistant to cefotaxime, ceftazidime, and, among others, all aminoglycosides including amikacin. The majority of representative isolates examined with macrorestriction analysis of genomic DNA (pulsed-field gel electrophoresis) were identical. The strain was susceptible to the innate antibacterial systems operative in fresh defibrinated blood from two adults. Combined human blood/antimicrobial drug assays documented the in vitro bactericidal activity of carbapenems (meropenem was slightly more effective than imipenem), fluoroquinolones (ciprofloxacin and trovafloxacin), and polymyxin B against this MAR strain of K. pneumoniae.
Comparative in vitro Antifungal Activity of Amphotericin B Lipid Complex, Amphotericin B and Fluconazole
Authors: Carrillo-Muñoz Alfonso-Javier , Quindós Guillermo , Tur Cristina , Ruesga Maite , Alonso Rocío , del Valle Oscar , Rodriguez Virginia , Arévalo M. Pilar , Salgado Javier , Martin-Mazuelos Estrella , Bornay-Llinares Fernando Jorge , del Palacio Amalia , Cuétara Marisol , Gasser Isabel , Hernández-Molina Juan Manuel , Pemán Javier
Published: April 2003

Amphotericin B (AMB) is considered the gold standard in the treatment of serious systemic mycoses in spite of its nephrotoxicity and adverse effects. Association with lipids enables larger doses of AMB to be given with a longer t½ and Cmax, without the toxic effects at lower concentrations. Liposome-encapsulated AMB shows a lower affinity for mammalian cells and improves Vd, thus decreasing toxicity. Amphotericin B lipid complex (ABLC) is an AMB formulation associated with a biodegradable phospholipid matrix (5% molar) from which the drug is released by cell phospholipases. ABLC is recommended for serious mycoses refractory to conventional antifungal therapy or when AMB is contraindicated. We compared the in vitro antifungal activity of ABLC, AMB and fluconazole (FLZ) against 328 strains of clinically significant opportunistic fungi using a microdilution method (NCCLS, M-27A). 64.9% of the yeasts were inhibited by MIC of ABLC ≤ AMB resulting in a similar or slightly superior efficacy compared to AMB when tested against Candida albicans, C. glabrata, C. guilliermondii, C. parapsilosis and C. tropicalis. Effectiveness against C. krusei was lower for ABLC (5.99 μg/ml for ABLC, 1.58 μg/ml for AMB). However, for Aspergillus fumigatus, the activities of AMB and ABLC were 1.62 and 2.46 μg/ml, respectively; A. niger 0.72 μg/ml, 0.76 μg/ml (ABLC and AMB, respectively); A. clavatus, A. candidus, A. tenuissima, A. corymbifera and Exophiala jeanselmei, Scedosporium spp. and Miceliophtora spp. showed a low susceptibility to both AMB formulations. ABLC is a useful alternative to AMB or FLZ for the treatment of severe fungal infections, due to the broad spectrum of antifungal actions observed in this study.
Ondansentron and Dexamethasone Treatment with Different Dosing Schedules (24 versus 32 mg) in Patients with Non-Small-Cell Lung Cancer under Cisplatin-Based Chemotherapy:A Randomized Stud y
Authors: Tsavaris N. , Kosmas Ch. , Vadiaka M. , Kanelopoulos P. , Kontos A. , Katsorida M. , Agelopoulou A. , Vrizidis N. , Fotia M. , Papoutsis K. , Koufos Ch.
Published: April 2003

The purpose of this study was to determine whether ondansentron given to patients with non-small-cell lung cancer (NSCLC) undergoing cisplatin-based chemotherapy, has better antiemetic activity administered every 6 or 8 h in controlling cisplatin-induced emesis. All patients had previously received 3 cycles of cisplatin-based chemotherapy at a dose of 100 mg/m2. Ondansentron was given according to two schedules in group A (50 patients) at a dose of 8 mg in 100 ml normal saline over 10 min i.v. infusion, together with dexamethasone 8 mg before the infusion of cisplatin, continued with both drugs at the same dose and administration after 8 and 16 h; in group B (50 patients) both drugs were administered before the infusion of cisplatin, continued after 6, 12 and 18 h. During the next 3 days, patients continued with tablets of dexamethasone 4 mg and ondansentron 8 mg, group A every 8 h, and group B every 6 h. The only difference in terms of antiemetic response that was noticed between the two groups was the number of patients experiencing nausea which was found increased in group A (n = 32) in comparison to group B (n = 25) (p < 0.022). No difference was noticed in the number of vomiting episodes and retches or emesis control, during the 3-day evaluation period after cisplatin infusion or in side effects. In conclusion, the total dose of 24 mg ondansentron during the acute phase of emesis is as effective as the total dose of 32 mg.
A Century of Helicobacter pylori
Authors: Kidd Mark , Modlin Irvin M.
Published: April 2003

The investigation of gastric bacteria properly began in the latter half of the nineteenth century when microscope resolution had sufficiently advanced. Whilst a bacterial etiology was demonstrated for dysentery, tuberculosis and syphilitic ulcers, problems in the isolation and culture of pure strains circumvented a role for bacteria in gastric pathology. Furthermore, dogma and the intellectual chorus were in harmony advocating that gastric acid was critical in ulcer disease. The consideration of a role for a pathogen or pepsin was regarded as whimsical in the context of mucosal ulceration. Indeed, the effects of acid inhibitory agents were held as gospel truth whilst the use of antibiotics or metallic ions were deemd to be quackery or at least ill judged. Nonetheless, spiral-shaped bacteria had been identified in both mucosa and gastric contents of patients as early as 1889. Elegant studies had documented the infectivity of these organisms, and suggested but not proven a causative role in gastric disease. The prescient identification by Doenges of organisms associated with gastritis in both man and monkey, was buried by the observations of Palmer, and an opportunity for early progress lost. It required two decades and Antipodean pathological perspicacity to elucidate the warren of previous archaic gastric bacterial misinformation. The subsequent marshalling of clinical and pathological data established the fatal flaw in the mucosa to be bacteria and not only acid on the mucus shore. It is now widely apparent that Helicobacter is ubiquitous, pathological and, a century after its initial discovery, still remains a paradox of as yet incompletely determined biological consequence. It is of note that an organic helical configuration has twice in this century provided biological information of unique import.
Overexpression of Cholecystokinin-B/ Gastrin Receptor Gene in the Stomach of Naturally Occurring Cholecystokinin-A Receptor Gene Knockout Rats
Authors: Miyasaka Kyoko , Kanai Setsuko , Ohta Minoru , Jimi Atsuo , Kono Akira , Funakoshi Akihiro
Published: April 2003

We examined the cholecystokinin (CCK)-B/gastrin receptor, H+/K+-ATPase and somatostatin gene expression, the histology and immunohistochemistry of gastrin and somatostatin of the stomach, plasma gastrin levels, and gastric acid secretion in naturally occurring CCK-A receptor gene knockout (Otsuka Long-Evans Tokushima fatty, OLETF) rats. The CCK-B/gastrin receptor, H+/K+-ATPase and somatostatin mRNAs were determined by Northern transfer analysis. The gastric acid secretion and the plasma gastrin level were measured in vivo. The levels of CCK-B/gastrin receptor mRNA in the forestomach and the glandular stomach in OLETF rats were 2-fold higher than those of control rats, although those of H+/K+-ATPase and somatostatin mRNAs were not different. Histological examination revealed thickening of the fundic mucosa, and hyperplasia and hypertrophy of parietal cells, although immunohistochemistry of gastrin and somatostatin revealed no significant difference from the control rats. Gastric acid secretion stimulated by gastrin or histamine was enhanced, whereas the fasting plasma gastrin level was not significantly different from that in control rats. The overexpression of CCK-B/gastrin receptor mRNA and the hyperfunction of parietal cells were observed in rats without CCK-A receptor gene expression.
Protein Kinase C Gene Expression in Dispersed Guinea-Pig Gastric Parietal Cells
Authors: Muramatsu Shigeru , Tani Norio , Miwa Takeshi , Kimura Minoru
Published: April 2003

Background Aims: It has been implicated that protein kinase C (PKC) is involved in gastric acid secretion. The purpose of this study is to examine whether mRNA expression of PKC isoforms is observed in guinea-pig gastric parietal cells, and whether such PKC expression is regulated by agonists that stimulate gastric acid secretion. Methods: Expression of PKC mRNA was assessed using isolated guinea-pig gastric parietal cells treated with or without three kinds of agonists by Nothern blot analysis. Results: (1) α, γ and ζPKC mRNAs were expressed in guinea-pig gastric parietal cells; (2) both carbachol and gastrin increased the level of α and γPKC mRNAs, but synthesis of ζPKC mRNA was not affected by these agonists, and (3) histamine did not affect the expression level of α, γ and ζPKC mRNAs. Conclusion: α and γPKC isoforms may be involved in the regulation of gastric acid secretion.
Activation of Epithelial Cells in Gastritis
Authors: El Kaissouni J. , Bene M.C. , Faure G.C.
Published: April 2003

Background: Helicobacter pylori is now recognised to be the major cause of antral gastritis and a risk factor for further development of gastric cancer. This infection results in local inflammation and a modification of gastric mucosal epithelial cell characteristics. Systematic investigation for the expression of the secretory component by gastric epithelium in a personal historical series of biopsy specimens showed the expression of this activation marker in 38% of the cases, 19% also showing clear signs of H. pylori infection. Aims: To further appreciate the activation of epithelial cells in the chronic gastric inflammation associated with H. pylori infection and other types of gastritis without consideration of the grade of gastritis. Methods: Punch gastric biopsies from 36 patients (10 patients with confirmed H. pylori gastritis, 16 patients with non-H. pylori gastritis and 10 controls) were tested for the expression of ICAM-1/CD54, HLA-DP, -DQ, -DR, secretory component and bcl-2 by immunofluorescence. Results: Up-regulation of most markers was observed both in H. pylori and non-H. pylori gastritis, although secretory component, CD54 and DP expression was more closely associated with H. pylori gastritis. Conclusion: H. pylori infection appears to activate gastric epithelial cells more strongly than other types of gastritis. This suggests an active relationship between this bacterium and epithelial cells. Investigation of the up-regulationship between this bacterium and epithelial cells. Investigation of the up-regulation of secretory component, ICAM-1/CD54 or DP in gastric biopsies may serve as extensive markers in search of H. pylori gastric infections.
Increased Hepatocyte Growth Factor Content in Rat Stomach during Omeprazole Treatment
Authors: Kinoshita Yoshikazu , Hassan Md. Sazzad , Kawamura Makoto , Matsushima Yumi , Okada Akihiko , Maekawa Toru , Fukui Hirokazu , Waki Shinya , Kishi Kiyohiko , Chiba Tsutomu
Published: April 2003

Background and Aims: Hepatocyte growth factor (HGF) is a potent mitogen of gastric epithelial cells, and its production is stimulated during the healing of gastric mucosal lesions. In this study, the effect of a proton pump inhibitor, omeprazole, on the production and degradation of HGF in the stomach was examined to elucidate the mechanism of the omeprazole-induced acceleration of gastric mucosal healing. Methods: Indomethacin-induced gastric mucosal lesions were induced in rats with or without omeprazole pretreatment. HGF gene expression and the content of HGF was investigated in the rat stomach. HGF degradation by gastric juice was also tested. Results: In omeprazole-treated rats, the healing of gastric mucosal lesions was accelerated in comparison with those of untreated rats. Although omeprazole treatment did not enhance the indomethacin-induced increase in HGF gene expression, it significantly augmented the gastric HGF content. Furthermore, omeprazole increased the gastric content not only of the inactive but also of the active heterodimeric form of HGF, and this appeared to be due to the inhibition of the HGF degradation by gastric juice. Conclusion: Omeprazole-induced acceleration of gastric mucosal healing may be mediated at least in part by the reduced degradation of HGF in the stomach.
Neural Control of the Gallbladder: An Intracellular Study of Human Gallbladder Neurons
Authors: Hillsley K. , Jennings L.J. , Mawe G.M.
Published: April 2003

Background/Aims: Gallbladder neurons are important governors of gallbladder function. In animal models, gallbladder ganglia can be regulated both by neural and hormonal inputs. The purpose of this study was to demonstrate the feasibility of obtaining recordings from human gallbladder neurons. Methods: Human gallbladders (n = 33) were bathed in oxygenated Krebs solution (37°C) containing the vital fluorescent stain 4-Di-2-ASP to localize the ganglia. Cells were characterized using conventional intracellular recording techniques. Results: The mean resting membrane potential of human gallbladder neurons was –51.2 ± 1.8 mV (n = 11). Depolarizing current pulses elicited only 1–4 spikes regardless of the amplitude or duration of the stimulus. Afterspike hyperpolarizations had a mean duration of 144.5 ± 19.2 ms (n = 10). Anodal break excitation was not recorded with hyperpolarizing current pulses. Fiber tract stimulation elicited fast excitatory postsynaptic potentials in all neurons tested. Conclusion: Intracellular recordings of human gallbladder neurons utilizing 4-Di-2-ASP are thus feasible, but are very problematic due to the density of connective tissue overlying the ganglia. As human and guinea pig gallbladder neurons have similar basic electrical properties, the guinea pig may be an appropriate model for further electrophysiological studies into gallbladder disease.
Human Pancreatic Secretory Trypsin Inhibitor
Authors: Marchbank T. , Freeman T.C. , Playford R.J.
Published: April 2003

Pancreatic secretory trypsin inhibitor is a potent protease inhibitor which was originally identified in the pancreas. It has subsequently been shown to be present in mucus-secreting cells throughout the gastrointestinal tract and also in the kidney, lung and breast. Its major roles are likely to be to prevent premature activation of pancreatic proteases and to decrease the rate of mucus digestion by luminal proteases within the stomach and colon. In addition, PSTI increases the proliferation of a variety of cell lines and stimulates cell migration, possibly acting via the EGF receptor. These findings suggest that PSTI may also be involved in both the early and late phases of the healing response following injury. Further studies including the production of transgenic overexpression and knockout models should help elucidate the physiological function of this peptide.
Increased Cytosolic Ca2+ Amplifies Oxygen Radical-Induced Alterations of the Ultrastructure and the Energy Metabolism of Isolated Rat Pancreatic Acinar Cells
Authors: Weber H. , Roesner J.P. , Nebe B. , Rychly J. , Werner A. , Schröder H. , Jonas L. , Leitzmann P. , Schneider K.-P. , Dummler W.
Published: April 2003

Background: Oxygen radicals have been implicated as important mediators in the early pathogenesis of acute pancreatitis, but the mechanism by which they produce pancreatic tissue injury remains unclear. We have, therefore, investigated the effects of oxygen radicals on isolated rat pancreatic acinar cells as to the ultrastructure, cytosolic Ca2+ concentration and energy metabolism. Methods: Acinar cells were exposed to an oxygen radical-generating system consisting of xanthine oxidase, hypoxanthine and chelated iron ions. Cell injury was assessed by LDH release and electron microscopy. Cytosolic Ca2+ levels and mitochondrial membrane potential were determined by flow cytometry; adenine nucleotide concentrations by HPLC. Mitochondrial dehydrogenase activity was measured by spectrophotometric assay. Results: Oxygen radicals damaged the plasma membrane as shown by a 6-fold LDH increase in the incubation medium within 180 min. At the ultrastructural level, mitochondria were the most susceptible to oxidative stress. In correlation to the pronounced mitochondrial damage, the mitochondrial dehydrogenase activity declined by 70%, whereas the mitochondrial membrane potential was enhanced by 27% after 120 min. Together this may cause the 85% decrease in the ATP concentration and the corresponding increase in ADP/AMP observed in parallel. In addition, an immediate 26% increase in cytosolic Ca2+ was found, a change which could be inhibited by BAPTA, reducing cellular damage. Conclusion: Cytosolic Ca2+ synergizes with oxygen radicals causing alterations of the ultrastructure and energy metabolism of acinar cells which might contribute to the cellular changes found in early stages of acute pancreatitis.
Constitutive Nitric Oxide Synthases in Rat Gastric Mucosa: Subcellular Distribution, Relative Activity and Different Carboxyl-Terminal Antigenicity of the Neuronal Form Compared with Cerebellum
Authors: Price Ken , Hanson Peter
Published: April 2003

Background/Aims: To investigate whether the neuronal form of nitric oxide (NO) synthase (nNOS) in gastric mucosa differed from nNOS in the brain in subcellular distribution or antigenicity, and to determine the relative activity of the endothelial form of NO synthase (eNOS) and nNOS in gastric mucosa. Methods: Subcellular fractionation, assay of enzyme activity by conversion of arginine to citrulline, and immunoblotting were employed. Results: 10% of NO synthase activity in gastric mucosa was particulate compared with 31% in the cerebellum. Immunoblotting demonstrated that gastric mucosal nNOS protein was essentially cytosolic and that eNOS was largely particulate. Combination of these results with measurements of enzyme activity suggested that 96% of gastric mucosal activity was contributed by nNOS. Experiments with an antiserum raised against the carboxyl-terminal hexadecapeptide of rat brain NO synthase suggested a difference in antigenicity between forms of nNOS from the cerebellum and gastric mucosa. This difference did not seem to result from alternative splicing of the primary transcript, and was not present after enrichment of nNOS by affinity chromatography using 2′,5′-ADP agarose. Conclusion: The form of nNOS in rat gastric mucosa is largely cytosolic and is the major constitutive activity. When first isolated gastric nNOS differs in antigenicity from the equivalent brain enzyme, probably as a result of an unstable post-translational modification, close to the carboxyl-terminus.