bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of the Flow Patterns among the Four Pulmonary Veins as Assessed by Transesophageal Echocardiography: Influence of Significant Mitral Regurgitation
Authors: Hwang Juey-Jen , Lin Jer-Min , Hsu Kwan-Lih , Lai Ling-Ping , Lin Jiunn-Lee , Tseng Yung-Zu , Lee Yuan-Teh , Lien Wen-Pin
Published: April 2003

Aims: To evaluate the correlation of the flow patterns of the four pulmonary veins as assessed by transesophageal echocardiography and the influence of significant mitral regurgitation on this correlation. Methods and Results: Eighty-eight patients with normal sinus rhythm and variable underlying cardiovascular diseases underwent transthoracic and transesophageal echocardiographic studies. Doppler flow of the four pulmonary veins could not be adequately interpreted in 19 patients (22%). The left atrial dimension of these patients was significantly larger than that of the patients with complete study of the flow in the four pulmonary veins (49 ± 6 vs. 43 ± 7 mm; p < 0.05). Of the 69 patients with complete evaluation of the four pulmonary veins, 48 patients without significant mitral regurgitation were analyzed as group A, and the remaining 21 patients as group B. The peak systolic and diastolic forward flow velocities of the four pulmonary veins were measured and the ratio of peak systolic (S) to diastolic (D) flow velocity was calculated. Group A had a significantly larger S/D ratio in all four pulmonary veins than group B (p < 0.05 in each pulmonary vein measurement). There was good correlation of the flow pattern represented as S/D ratio between left upper and lower pulmonary veins (r = 0.90) and between right upper and lower pulmonary veins (r = 0.89) in group A. The correlation of the flow pattern among the four pulmonary veins deteriorated in group B. Conclusion: Pulmonary veins on the same side share rather similar flow patterns in comparison with pulmonary veins on the opposite sides. The correlation of flow patterns among the four pulmonary veins is good in subjects without significant mitral regurgitation, but it worsens in patients with significant mitral regurgitation. Therefore, cautious interpretation of flow patterns of the four pulmonary veins in patients with significant regurgitation is indicated for grading the severity of mitral regurgitation.
Volume Measurement of the Left Ventricle in Children with Congenital Heart Defects: 3-Dimensional Echocardiography versus Angiocardiography
Authors: Heusch A. , Rübo J. , Krogmann O.N. , Bönig H. , Bourgeois M.
Published: April 2003

Background: Volume measurement of the left ventricle is currently done by 2-dimensional echocardiography or angiocardiography. However, for the calculation of volumes by these methods, geometrical assumptions must be made. For a precise ventricular volumetry, independent of mathematical assumptions, imaging techniques as the 3-dimensional echocardiography (3D-echo) are required, which permit the imaging of the real ventricular shape. The aim of the study was therefore to detect, whether 3D-echocardiography is suitable for left ventricular volumetry in children with congenital heart disease and whether the 3D-echocadiographically measured volumes correlate sufficiently well with angiocardiographically measured left ventricular volumes. Methods: 102 children with congenital heart disease were investigated. For angiocardiographic left ventricular volume measurement Simpson’s rule was used. Results were corrected with Lange’s correction factors. The 3D-echo data sets were registered with a rotating transthoracic transducer. Ventricular volumes were calculated after manual planimetry by summation of the volumes of the single slices. Results: The left ventricular volume could be calculated by 3D-echo in 83% of patients of all ages. In comparison to angiocardiography, the measured volumes were 0.6 ± 3.3 ml (0.9 ± 25.8%) or 7.1 ± 28.4 ml (7.4 ± 12.1%) smaller during systole or diastole, respectively. The correlation coefficients r2 were 0.89 for systolic and 0.93 for diastolic measurements after logarithmic transformation. Pressure or volume overload did not influence significantly the difference between the two methods. Conclusion: Transthoracic 3D-echocardiography with a rotating transmitter is feasible for volumetry of the left ventricle in most children. The volumes measured by 3D-echo were significantly smaller than those calculated from the angiocardiography by Simpson’s rule. The measurements were not influenced by the kind of load of the ventricle. The correlation between the two methods is good.
Failure of Thrombin Generation Markers to Triage Patients Presenting with Chest Pain
Authors: McKenzie Marcus E. , Pothula Anitha , Gurbel Paul A. , Fuzaylov Sergei Y. , O’Connor Christopher M. , Gattis Wendy A. , Serebruany Victor L.
Published: April 2003

Thrombin generation (TG) is an important pathogenic factor in acute coronary syndromes including acute myocardial infarction (AMI). Since the diagnostic utility of TG remains uncertain we sought to determine whether markers of TG may triage patients presenting to the Emergency Department with chest pain. Soluble plasma levels of prothrombin fragment 1+2 (F1+2), and thrombin/antithrombin III complexes (TAT) were determined by ELISA in 80 patients presenting with chest pain to the Emergency Department and compared with 20 controls. There were no differences in TG markers between patients with non-cardiac chest pain and healthy controls. Patients with unstable angina (UA), and congestive heart failure (CHF) did not differ from controls with respect to F1+2, and TAT was elevated in UA patients (6.05 ± 1.15 ng/ml, p = 0.033) when compared with controls (3.34 ± 0.20 ng/ml). Contrary to expectations, TAT levels at presentation with AMI were well below the concentrations observed in patiens with UA and CHF. Moreover, plasma F1+2 levels were significantly lower than in healthy controls (0.84 ± 0.10 ng/ml versus 1.22 ± 0.11, p = 0.026). At the time of presentation to the Emergency Department, F1+2 and TAT failed to suitably triage patients with chest pain. The surprisingly low levels of TG markers in AMI patients before applying intensive therapy and reperfusion strategies deserves further investigation.
Early-Onset Familial Dilatation of the Ascending Aorta
Authors: Beghetti Maurice , Steinmann Beat , Didier Dominique , Kalangos Afksendiyos , Bottani Armand
Published: April 2003

A mother and her two children with idiopathic ascending aortic dilatation are reported. This provides further evidence that genetic factors are involved in the etiology of aortic aneurysms and calls for screening first-degree family members, including children, of young adult patients diagnosed with this condition.
Beta-Blockers after Myocardial Infarction: Do Benefits Ever Outweigh Risks in Asthma?
Authors: Chafin Carol C. , Soberman Judith E. , Demirkan Kutay , Self Timothy
Published: April 2003

β-Blockers are well documented to prolong life in patients after myocardial infarction (MI), yet patients who also have asthma are frequently and understandably denied this therapy. We reviewed the literature (via MEDLINE) for the past 35 years for β-blocker-induced asthma, and reexamined potential β-blocker use in the context of NIH guidelines for asthma classification and management. Because β-blockers can cause fatal or life-threatening asthma, their use should be avoided in moderate to severe persistent asthmatics. Benefits of low-dose β1-blockers (e.g. atenolol 50 mg daily) may outweigh risks in some patients with mild intermittent or well-controlled mild persistent asthma. Further study is needed to verify that low doses of β1-blockers are effective in prolonging life after MI, and that use specifically in mild intermittent or mild persistent asthma per NIH classification is safe.
A Left Atrial Thrombus Is Not an Absolute Limitation to Balloon Mitral Commissurotomy for Patients with Mitral Stenosis
Authors: Lin Shoa-Lin , Chen Chen-Huan , Hsu Tsu-Lieh , Chang Mau-Song , Chiang Hung-Ting , Liu Chun-Peng
Published: April 2003

Previous reports did not encourage balloon mitral commissurotomy (BMC) when left atrial (LA) thrombi were located beyond LA appendage. We hypothesize that LA thrombi may be resolved in some patients after anticoagulant therapy, and BMC can be performed subsequently. In the present study, we used transesophageal echocardiography (TEE) to evaluate the effects of anticoagulant on LA thrombi in patients with mitral stenosis, to compare the clinical differences between patients with (group A) and without (group B) resolution of LA thrombi, and to evaluate the safety of subsequent BMC in these patients. TEE was performed on 190 consecutive patients with mitral stenosis; 14 (7.4%) of them were found with LA thrombi. Serial TEE was performed and optimal anticoagulant therapy was achieved in all 14 patients. The thrombi were located within the LA appendage in 6 cases, attached to the LA posterior wall in 5, posterior wall and interatrial septum in 1, and LA appendage and posterior wall in 2. Based on the 6-month TEE follow-up, we found that the LA thrombi disappeared in 8 (57.2%) patients (group A) and persisted in 6 patients (group B). LA thrombi resolved within 3 months in 7 group A patients (87.5%). Furthermore, the resolution of LA thrombi was more frequently observed in patients either with a smaller LA dimension (51.9 ± 3.4 vs. 57.8 ± 4.8 mm, p = 0.02) or with their thrombi located inside their LA appendage (p = 0.03). No differences in other clinical and echocardiographic variables were noted between these two groups. Subsequently, group A patients underwent BMC without complications of systemic embolization. In conclusion, LA thrombi can be resolved after optimal anticoagulant therapy in a considerable proportion of patients with mitral stenosis. Serial TEE studies are helpful to observe LA thrombus resolution; they may also be useful in planning the treatment strategy.
Relationship between Endogenous Sex Hormone Levels, Lipoproteins and Coronary Atherosclerosis in Men Undergoing Coronary Angiography
Authors: Kabakci Giray , Yildirir Aylin , Can Ilknur , Unsal Ibrahim , Erbas Belkis
Published: April 2003

This study was carried out in order to investigate the relationship between endogenous sex steroid hormones and coronary artery disease (CAD). Three hundred and thirty-seven men undergoing coronary angiography were enrolled in the study. Total testosterone, estradiol, free testosterone levels in men with CAD (n = 213) were compared to those of men without CAD (n = 124). No significant differences were found in the serum concentrations of estradiol, total and free testosterone and serum lipid profile between the two groups. Total and free testosterone were negatively (p < 0.05 to p < 0.001) and estradiol was positively (p < 0.05) correlated with age in both groups. Total cholesterol and low-density-lipoprotein levels were positively correlated with the level of free testosterone (r = 0.221, p < 0.01; r = 0.173, p < 0.05, respectively), and high-density-lipoprotein levels were negatively correlated with total testosterone in patients with CAD (r = –0.166, p < 0.05). The results of this study do not support the role of sex steroid hormones in CAD. However, the relationship between sex steroids and serum lipids needs further clarification.
Cardiac Effects of Persistent Hemodialysis Arteriovenous Access in Recipients of Renal Allograft
Authors: De Lima José Jayme G. , Campos Vieira Marcelo Luis , Molnar Laszlo J. , Medeiros Caio Jorge , Ianhez Luís Estevan , Krieger Eduardo M.
Published: April 2003

In hemodialysis patients, large arteriovenous (AV) fistulas for vascular access may cause ventricular hypertrophy and high-output cardiac failure. The long-term cardiac consequences of functional AV fistulas in renal transplant patients are unclear. A precise knowledge of these consequences is important to decide if and when such fistulas should be closed in successfully transplanted patients. In this retrospective study including 61 stable renal transplant patients with adequate renal function (serum creatinine <2.0 mg/100 ml), echocardiography was performed in 39 patients with a functional AV fistula (group 1) and in 22 whose fistulas had been closed, for esthetic reasons, within 2 months postoperatively (group 2). The volume flow of the fistulas, measured in 22 randomly selected individuals of group 1, was 900 ± 350 ml/min (range 500–1,600). Patients of group 1 were older (40 ± 12 vs. 33 ± 12 years, p < 0.05), had longer duration of the fistula (62 ± 31 vs. 36 ± 30 months, p < 0.05), higher body mass index (24 ± 4 vs. 22 ± 3 kg/m2, p < 0.05), systolic (154 ± 24 vs. 138 ± 18 mm Hg, p < 0.05) and diastolic (96 ± 12 vs. 89 ± 11 mm Hg, p < 0.05) blood pressure and increased left ventricular (LV) end-diastolic dimension (53 ± 5 vs. 49 ± 5 mm, p < 0.01). LV mass, cardiac index, ejection fraction and the proportion of patients with LV hypertrophy were comparable in the two groups. LV end-diastolic dimension was positively and independently influenced only by the presence of the AV fistula (p < 0.01) after adjusting for age, duration of the fistula, body mass index, systolic and diastolic blood pressure and the nature of the antihypertensive drugs used. In conclusion, the persistence of large, high-flow AV fistulas for prolonged periods of time had little impact on cardiac morphology and function of stable renal transplant patients with adequate renal function. The data do not support routine closure of these fistulas in all renal transplant patients.
Changes of Plasma Tissue Factor and Tissue Factor Pathway Inhibitor Antigen Levels and Induction of Tissue Factor Expression on the Monocytes in Coronary Artery Disease
Authors: Kim Hyun Kyung , Song Kyung Soon , Park Young Sook , Yun Young-Sup , Shim Won Heum
Published: April 2003

Background: Several studies have shown that thrombosis and inflammation play an important role in the pathogenesis of coronary artery disease (CAD). Tissue factor (TF) is responsible for the thrombogenicity of the atherosclerotic plaque and plays a key in triggering thrombin generation. The aim of this study was to assess the levels of TF and tissue factor pathway inhibitor (TFPI) in patients with angiographically documented CAD and also to evaluate TF induction on monocytes in vitro in the presence of these plasmas from patients with CAD. Methods: Plasma antigen levels of soluble TF and TFPI were measured in 65 CAD patients and 22 healthy controls. Surface TF expression on monocytes from a healthy donor treated with plasma samples was evaluated by flow cytometry with a direct double-color immunofluorescence technique. Results: Significantly elevated levels of both TF and TFPI were found in CAD patients compared with healthy controls (303.6 ± 134.1 vs. 187.3 ± 108.7 pg/ml, p < 0.05; 85.2 ± 48.6 vs. 65.0 ± 29.0 ng/ml, p < 0.05). By flow cytometry, monocytes from a healthy donor displayed higher TF antigen expression when incubated in the presence of CAD plasmas than in control plasmas (34.6 ± 10.7 vs. 23.2 ± 10.2%, p < 0.05). Conclusions: The high levels of circulating TF are present in CAD, which were not sufficiently inhibited by the elevated TFPI plasma levels. Although the source of circulating TF is unclear, TF induction of monocytes by plasma from CAD patients may contribute to the hypercoagulable state.
Combining Necrosis and Platelet Markers for Perfecting Myocardial Infarction Rule Out: How Close Are We?
Authors: Nair Girish V. , Gurbel Paul A. , Fuzaylov Sergey Y. , Davis Christopher J. , Ohman E. Magnus , Bahr Raymond D. , Christensen Robert H. , Serebruany Victor L.
Published: April 2003

Each year, at least 5 million patients in the United States present to hospital emergency departments with the complaint of chest pain, and more than 10% of them will be diagnosed with acute myocardial infarction. One of the foremost tasks of the emergency department physician is to avoid unnecessary admissions and concomitantly to minimize the number of patients discharged home inappropriately. Currently available diagnostic tools, including the electrocardiogram and myocardial markers, have several shortcomings, including low specificity, and delayed sensitivity for the timely detection of myocardial necrosis. Therefore, the search for better methods of rapidly identifying patients with unstable coronary syndromes is one of the utmost priorities of modern emergency medicine. Available biochemical diagnostic tools are discussed in this review, focusing on the potential benefits of combining myocardial necrosis markers with indicators of platelet activation. It is hypothesized that such a combined approach may be more powerful in myocardial infarction risk stratification than separate marker determination.
Cardiogenic Shock: Single Center Experience with and without On-Site Catheterization Facilities
Authors: Barbash Israel M. , Ilia Reuben , Gilutz Harel , Boyko Valentina , Battler Alexander , Leor Jonathan
Published: April 2003

Background: The beneficial effect of on-site catheterization facilities on the survival of all patients with myocardial infarction complicated by cardiogenic shock has been questioned. Our objective was to evaluate the impact of the availability of on-site catheterization facilities on the outcome of unselected patients with cardiogenic shock. Methods and Results: We studied the hospital records of 70 consecutive patients with cardiogenic shock admitted to our intensive coronary care unit during 1990–1996, and compared two groups of patients: those admitted before (n = 34) and after (n = 36) the opening of our catheterization laboratory. Patients admitted when the catheterization laboratory was available were of similar age, but included fewer males and fewer patients with prior myocardial infarction. Following the activation of the catheterization laboratory, utilization rates of coronary angiography, percutaneous transluminal coronary angioplasty and intra-aortic balloon pump increased, compared with the previous period. However, there was no improvement in in-hospital (88 vs. 83%; p = 0.7) and 30-day mortality (91 vs. 86%; p = 0.7) before versus after the activation of our catheterization laboratory. Twelve patients selected to cardiac catheterization (9 underwent percutaneous transluminal coronary angioplasty) experienced lower in-hospital and 30-day mortality compared with patients who were not selected (58 vs. 96, and 67 vs. 96%, respectively; p < 0.02). Conclusions: Following the activation of the catheterization laboratory, the mortality of the entire population of cardiogenic shock patients remained relatively unchanged. Still, a small subgroup of these patients selected for urgent cardiac catheterization had a lower mortality compared with patients who were not selected.
Segmental Wall Motion Abnormalities in an Individual with Idiopathic Pulmonary Hemosiderosis
Authors: Bavry Anthony A. , Knoper Steven , Alpert Joseph S.
Published: April 2003

Idiopathic pulmonary hemosiderosis (IPH) is a rare condition characterized by diffuse pulmonary hemorrhage of unknown etiology. Cardiac involvement in the form of myocarditis and right ventricular hypertrophy have been reported to occur in association with IPH, although findings on echocardiography have not been described. Herein is presented a case of an adult with IPH and echocardiographic abnormalities.
Tachycardias in Infants, Children and Adolescents: Safety and Effectiveness of Radiofrequency Catheter Ablation
Authors: Lee Sung-Jae , Schueller Walter Ch.
Published: April 2003

Radiofrequency catheter ablations provide an effective control of a variety of supraventricular and ventricular tachycardias in adults. This study was designed to evaluate the efficacy and safety of radiofrequency catheter ablations in infants, children and adolescents. Ninty-three ablations were performed in 84 patients ranging from 5 months to 18 years of age. All but 1 patient were successfully treated (98.8%). Two patients required 1 and 2 additional attempts to achieve success. Tachyarrhythmic episodes recurred in 4 patients within 1–5 months after ablation, which were successfully treated by repeating the intervention. Significant complications occurred in 3 of the ablations (3.2%). Although radiofrequency ablations are very effective and safe in pediatric patients, indications should be restricted in patients younger than 4 years because of a higher risk of possibly life-threatening complications.
Effects of Intracoronary Tissue-Type Plasminogen Activator Treatment in Kawasaki Disease and Acute Myocardial Infarction
Authors: Nakagawa Masao , Watanabe Noriko , Okuno Masahiko , Okamoto Nobuhiko , Fujino Hidetoshi
Published: April 2003

We retrospectively studied 3 patients with Kawasaki disease (KD) and acute myocardial infarction (AMI) who were treated with intracoronary administration of tissue-type plasminogen activator (t-PA). Two-dimensional echocardiogram on the next day of the treatment revealed reduction of thrombus and improvement of the cardiac function in all 3 patients. However, a 12-month-old patient treated with 200,000 U/kg of t-PA at 48 h after the onset of AMI died of recurrent myocardial infarction. The other 2 patients treated with 400,000 and 800,000 U/kg, respectively, showed clear, though not prompt, improvement in clinical symptoms and laboratory data. The intracoronary thrombolytic therapy using high-dose t-PA appears effective in treating AMI associated with KD.
In vitro Antibacterial Activity of Trovafloxacin and Five Other Fluoroquinolones
Authors: Montanari M.P. , Prenna M. , Mingoia M. , Ripa S. , Varaldo P.E.
Published: April 2003

The in vitro inhibitory and bactericidal activities of the investigational fluoroquinolone trovafloxacin were studied and compared with those of five other fluoroquinolones (ciprofloxacin, ofloxacin, pefloxacin, rufloxacin and sparfloxacin) against a wide range of clinical isolates from Italian hospitals. Against gram-positive bacteria, trovafloxacin was overall more active than the other antibiotics tested, including sparfloxacin, another gram-positive-oriented fluoroquinolone, and was active against all ciprofloxacin-resistant streptococci, enterococci, and listeriae, all ciprofloxacin-resistant Staphylococcus aureus isolates and most ciprofloxacin-resistant coagulase-negative staphylococci. Its antistaphylococcal activity was not affected by oxacillin resistance or susceptibility of the isolates, nor was its antipneumococcal activity affected by whether isolates were susceptible or resistant to penicillin. Against gram-negative bacteria, trovafloxacin retained a high potency mostly comparable with that of ciprofloxacin. Rufloxacin and pefloxacin were less active than the other fluoroquinolones against most test strains of both gram-positive and gram-negative organisms. Trovafloxacin minimal bactericidal concentrations usually equalled or exceeded by 2–4 times the minimal inhibitory concentration values, indicating that the compound is overall highly bactericidal.
Effects of a New Topic Amikacin Formulation on Chemotaxis and Release of Profibrotic Factors by Human Monocytes
Authors: Baroni A. , Tufano M.A. , Bolognino P. , Buttini G. , Catalanotti P.
Published: April 2003

Aminoglycosides, widely used because of their large-spectrum antibiotic effects, should not interfere with the healing process of an ulcer or an infected wound. We evaluated the effects of amikacin or the excipients present in the topic formulation BG 90, powder 2.5% (Boniscontro e Gazzone S.r.l., Rome, Italy), on human monocyte chemotaxis and the release of profibrotic factors by resting or lipopolysaccharide (LPS)-activated monocytes. The chemotactic response of monocytes to zymosan-activated serum is not modified in vitro by pre-incubation of the cells with amikacin (2 and 10 µg/ml/106 cells) or excipients. Unstimulated monocytes did not secrete appreciable amounts of cytokines. Vice versa, amikacin-stimulated cells released platelet-derived growth factor AB (PDGF-AB) (about 340 pg/ml), transforming growth factor (TGF)-β1 (about 10 pg/ml), and tumour necrosis factor (TNF)-α (over 1,100 pg/ml); among excipients, ZnO and vitamin E induced PDGF-AB release (about 320 and, respectively, 200 pg/ml), while stimulation of monocyte monolayers by the other excipients did not lead to appreciable cytokine release. As expected, LPS-activated human monocytes produced PDGF-AB, TGF-β1, and TNF-α. When monocytes were co-stimulated with LPS and amikacin, the PDGF-AB and TGF-β1 values almost overlapped with those from the stimulation of cells with LPS alone, while TNF-α production was slowly reduced. The results show a stimulating effect of aminoglycoside on the production of profibrotic factors and, therefore, on the healing process of wounds in addition to a modulating effect on the production of pro-inflammatory cytokines like TNF-α. Moreover, ZnO and tocopherol (free-radical scavengers), used as excipients in the topic formulation, induce the release of growth factors with profibrotic activity (PDGF-AB). Further research is warranted to explore the effects of this formulation in vivo, verifying whether the association of the antibiotic with scavengers has a double advantage in topical amikacin: on the one hand, it could limit the damage from free radicals, and on the other it could favour tissue healing.
A Cluster of Nosocomial Cross-Infection Due to Multiple Antibiotic-Resistant Acinetobacter baumannii:Characterization of the Strain and Antibiotic Susceptibility Studies
Authors: Traub Walter H. , Geipel Udo , Schwarze Isabel , Bauer Dierk
Published: April 2003

A multiple antibiotic-resistant (MAR) strain of Acinetobacter baumannii caused nosocomial cross-infection among 3 patients of a surgical intensive care unit. The isolates were of identical biochemical profile (77776 S–U–) and serotype (serovar 36) and identical in terms of pulsed-field gel electrophoresis macrorestriction (SmaI, ApaI) analysis. This MAR strain was susceptible only to netilmicin, tobramycin, imipenem, meropenem, polymyxin B, and trovafloxacin. The minimal bactericidal concentrations of imipenem and meropenem were markedly higher than the corresponding minimal inhibitory concentrations against this strain. Combined fresh defibrinated human blood (65 vol%) and antimicrobial drug assays yielded the following results: polymyxin was the most rapidly bactericidally effective antibiotic in the presence of blood and in broth. Tobramycin and netilmicin were efficacious in 65 vol% blood. Imipenem was slightly more effective than meropenem in broth, whereas both carbapenems sterilized blood-containing assay tube contents. Trovafloxacin failed to achieve bactericidal activity (to 99.9% kill) in the presence of blood, presumably because this strain was resistant to ciprofloxacin and borderline susceptible to ofloxacin. Trovafloxacin combined with either imipenem or meropenem yielded an indifferent effect. However, the combination of trovafloxacin (2 μg/ml) plus tobramycin (1 μg/ml) achieved sterilization of tube contents in the presence of blood within 4 h after exposure and in broth following extended (overnight) incubation. This MAR strain of A. baumannii was high-level resistant to rifampin; thus the combination of polymyxin B plus rifampin proved indifferent.
On the Inhibitory Activities of a New Boron Compound and Ultrasound against the Mouse Ascites Tumour
Authors: Sur Pratima , Ghosh P. , Bag S.P. , Sur B. , Chatterjee S.N.
Published: April 2003

The inhibitory effects of a new boron compound, dihydroxy (oxybiguanido) boron (III) hydrochloride monohydrate (HB), and ultrasound (US) of a frequency 25 kHz on the growth of ascites tumour in female Swiss mice were studied by monitoring the survival, weight of tumour-associated material, tumour cell count, serum alkaline phosphatase activity and the haematological parameters of the treated animals. 5-Fluorouracil (5-FU), a well-known anticancer agent, was used as positive control. While HB exhibiited a very significant antitumour action, US alone produced a small but significant inhibitory effect. The combination of US with HB or 5-FU produced an extra antitumour action as compared to the actions of these chemicals used singly. The mechanisms of action of the new boron compound (HB) and US are discussed.
Gastrointestinal Damage Induced by Cytostatic Treatment Does not Affect the Bioavailability of Co-Trimoxazole
Authors: Nyhlén A. , Johnsson A. , Höglund P. , Ljungberg B. , Nilsson-Ehle I.
Published: April 2003

Twelve lymphoma patients received prophylaxis with co-trimoxazole during cytostatic treatment according to the MACOP-B regimen with cyclophosphamide, doxorubicin, vincristine, methotrexate, bleomycin, folinic acid and prednisone. Gastrointestinal mucosal damage from cytostatic treatment was estimated by WHO toxicity scores. No correlation was found between the degree of gastrointestinal damage and the presumed bioavailability of co-trimoxazole as estimated from serum levels of trimethoprim and sulphamethoxazole. The serum concentrations were above the minimum inhibitory concentration for Escherichia coli, Staphylococcus aureus and coagulase-negative staphylococci irrespective of the degree of toxicity. There is no apparent reason to change the dosing regimen of prophylactic co-trimoxazole when there is clinical evidence of damage to the gastrointestinal mucosa induced by chemotherapy.
Evaluation of Phototoxic Potential of Gemifloxacin in Healthy Volunteers Compared with Ciprofloxacin
Authors: Vousden Marika , Ferguson James , Richards Justin , Bird Nicholas , Allen Ann
Published: April 2003

This double-blind, randomized, parallel-group comparative study investigated the phototoxic potential of gemifloxacin mesylate, a potent, novel fluoroquinolone antimicrobial. Forty healthy male and female volunteers received repeat dosing for 7 days with 160 mg or 320 mg of gemifloxacin (o.d., p.m.), 500 mg of ciprofloxacin (b.d.) or placebo (b.d.). On day 5 (large step) and day 6 (small step), graded series of wavebands were irradiated onto the back of each volunteer (phototesting). Skin reactions were assessed 0–30 min (immediate erythema) and 24 and 48 h (delayed erythema) after irradiation. Both gemifloxacin, 320 mg o.d., and ciprofloxacin, 500 mg b.d., were associated with mild phototoxicity following 7 days of administration. The range of mean phototoxic indices (the ratio of minimal erythemal dose at baseline compared with that on day 7 at the end of dosing) was 1.00–2.19 for gemifloxacin and 0.97–2.23 for ciprofloxacin. The abnormal responses occurred within the ultraviolet A region (335–365 ± 30 nm) and were maximal at 24 h. Susceptibility to phototoxicity had cleared 48 h after stopping the drug. The phototoxicity observed with gemifloxacin, 160 mg o.d., was lower than that at the higher dose and similar to that of placebo, suggesting that gemifloxacin phototoxicity is dose dependent. There were no clinically important changes in the safety profiles of gemifloxacin and ciprofloxacin compared with placebo in healthy volunteers after 7 days of repeat dosing. This study demonstrated that gemifloxacin, 320 mg o.d. given for 7 days, has a low potential to cause mild photosensitivity which is similar to that of ciprofloxacin, 500 mg b.d., given for the same period.
In vitro Cytotoxicity of Three 4,9-Diazapyrenium Hydrogensulfate Derivatives on Different Human Tumor Cell Lines
Authors: Roknić S. , Glavaš-Obrovac Lj. , Karner I. , Piantanida I. , Žinić M. , Pavelić K.
Published: April 2003

DNA intercalating agents interfere with DNA’s role as a template in replication and transcription by inserting an intercalator molecule between adjacent base pairs. We synthesized three potential novel intercalators, 4,9-diazapyrenium hydrogensulfate derivatives: 5,10-diphenyl-4,9-dimethyl-4,9-diazapyrenium hydrogensulfate (FDAP), 4,9-dimethyl-4,9-diazapyrenium hydrogensulfate (GDAP) and 2,4,7,9-tetramethyl-4,9-diazapyrenium hydrogensulfate (MDAP) and tested their biological effects in vitro on four human tumor cell lines (SKBr3: breast carcinoma, HeLa: cervical carcinoma, CaCo2: colon carcinoma and SW620: poorly differentiated cells from lymph node metastasis of colon carcinoma). Cytotoxic effects on cell growth and viability were determined using tetrazolium dye (MTT) assay. DNA synthesis and proliferation of treated cells were studied by the [3H]-thymidine incorporation test. DNA fragmentation was analyzed by agarose gel electrophoresis. The growth inhibitory effect was cell-specific and dose-dependent. The most pronounced antiproliferative effect was observed on SKBr3 cells for FDAP (10–5 M) 91.8%, for MDAP (10–5 M) 85.3% and on SW620 cells for GDAP (10–5 M) 65.3%. The DNA ladder fragmentation of treated HeLa and SKBr3 cells, as a hallmark of apoptosis, was observed. Based on specific DNA fragmentation, morphological changes (reduced cell volume, round cell shape, condensed chromatin) and growth inhibition of treated human tumor cells we conclude that tested substances induced apoptotic cell death.
Comparative in vitro Activity of S-4661, a New Parenteral Carbapenem, and Other Antimicrobial Agents against Respiratory Pathogens
Authors: Watanabe Akira , Takahashi Hiroshi , Kikuchi Tohru , Kobayashi Takao , Gomi Kazunori , Fujimura Shigeru , Tokue Yutaka , Nukiwa Toshihiro
Published: April 2003

The activity of S-4661, a new parenteral carbapenem antibiotic, was evaluated against 202 recent clinical isolates of respiratory pathogens. S-4661 was similar to or 2 times more active than imipenem, meropenem, and biapenem, and 8–128 times more active than ceftazidime against gram-positive bacteria. Against gram-negative bacteria, S-4661 was slightly less active than meropenem, but 2–8 times more active than the other agents. In particular, against Pseudomonas aeruginosa S-4661 showed the most potent activity. Thus it was found that S-4661 possesses a potent and well-balanced activity against respiratory pathogens.
Perioperative Infection Prophylaxis and Risk Factor Impact in Colon Surgery
Authors: Rau H.G. , Mittelkötter U. , Zimmermann A. , Lachmann A. , Köhler L. , Kullmann K.H.
Published: April 2003

Background: A prospective observational study was undertaken in 2,481 patients undergoing elective colon resection in 114 German centers to identify optimal drug and dosing modalities and risk factors for postoperative infection. Methods: Patients were pair matched using six risk factors and divided into 672 pairs (ceftriaxone vs. other cephalosporins, group A) and 400 pairs (ceftriaxone vs. penicillins, group B). End points were local and systemic postoperative infection and cost effectiveness. Results: Local infection rates were 6.0 versus 6.5% (group A) and 4.0 versus 10.5% (group B); systemic infection rates in groups A and B were 4.9 versus 6.3% and 3.3 versus 10.5%, respectively. Ceftriaxone was more effective than penicillins overall (6.8 vs. 17.8%, p < 0.001). Length of postoperative hospital stay was 16.2 versus 16.9 days (group A) and 15.8 versus 17.6 days (group B). Of the six risk factors, age and concomitant disease were significant for systemic infection, and blood loss, rectum resection and immunosuppressive therapy were significant for local infection. Penicillin was a risk factor compared to ceftriaxone (p < 0.0001). Ceftriaxone saved ∈160.7 versus other cephalosporins and ∈416.2 versus penicillins. Conclusion: Clinical and microbiological efficacy are responsible for the cost effectiveness of ceftriaxone for perioperative prophylaxis in colorectal surgery.
Polyamine Uptake Across the Basolateral Membrane of the Enterocyte Is Mediated by a High-Affinity Carrier
Authors: Milovic Vladan , Caspary Wolfgang F. , Stein Jürgen
Published: April 2003

Background/Aims: Polyamine uptake from the circulation plays an important role in the maintenance of the intracellular polyamine content during extensive proliferation in intestinal mucosal cells. Methods: Isolated basolateral membrane vesicles of the rabbit enterocyte were used to characterize polyamine transport across the basolateral side of the intestinal epithelium. Incorporation of spermidine and spermine into the basolateral membrane was rapid, although 30–60% of polyamines were initially bound to the basolateral membrane. In order to avoid the influence of binding on the actual uptake into the vesicles, polyamine incorporation was measured at 37 and 4°C, and kinetic parameters were calculated from the difference in polyamine incorporation rates at these temperatures. Results: Uptake kinetics was saturable, with Km values of 13.34 and 12.35 µmol/l and Vmax of 159 and 105 pmol/mg protein/min for spermidine and spermine, respectively. It was also temperature dependent, with Q10 values (calculated between uptake velocities at 37 and 25°C) of 2.56 for spermidine and 1.90 for spermine. At physiological pH, polyamine uptake was at its highest. Since at this pH polyamines are fully charged, charge might be essential for polyamines to be taken up across the basolateral membrane. Polyamine uptake was inhibited by di-, tri- and tetracations, and there was no evidence for sodium cotransport. Transport of putrescine was not inhibited by spermine and spermidine, although spermidine inhibited spermine uptake in a competitive manner, with Ki of 127 µmol/l. Conclusion: These results imply that a saturable high-affinity transport system for polyamine does exist at the basolateral side of the enterocyte. Such a transport system may be responsible for the active transport of polyamine into rapidly proliferating enterocytes.
Relationship between Fecal Bile Acids and the Occurrence of Colorectal Neoplasia in Experimental Murine Ulcerative Colitis
Authors: Kajiura Ken , Ohkusa Toshifumi , Okayasu Isao
Published: April 2003

Objective: The possible role of fecal bile acids in colorectal carcinogenesis in ulcerative colitis has been reported. In this study, we investigated the relationship between fecal bile acids and the occurrence of colorectal neoplasia in experimental murine colitis induced by dextran sulfate sodium. Methods: Colorectal neoplasia in experimental colitis was induced by dextran sulfate sodium subsequent to a single azoxymethane pretreatment. Fecal bile acids were analyzed by gas-liquid chromatography. Results: Multiple high-grade dysplasias (intramucosal adenocarcinoma) and inflammatory changes were seen in all mice administered dextran sulfate sodium and azoxymethane. Inflammatory changes were also observed in all mice given dextran sulfate sodium only, while neither tumor nor inflammatory changes were detected in any of the control mice. Significant increases in cholic acid were observed in the mice of the colorectal tumor and experimental colitis groups during the experimental period, while in the control mice, no significant changes in fecal bile acids were obseved. Conclusion: It is suggested that fecal cholic acid and colitis may be intimately related to the development of colorectal neoplasia in this experimental model of murine colitis as well as in ulcerative colitis.
Implications of Tachykinins and Calcitonin Gene-Related Peptide in Inflammatory Bowel Disease
Authors: Holzer Peter
Published: April 2003

Calcitonin gene-related peptide (CGRP) and the preprotachykinin A gene-derived peptides substance P (SP) and neurokinin A (NKA) are expressed in extrinsic primary afferent nerve fibres and intrinsic enteric neurons of the gut. The actions of tachykinins on the digestive effector systems are mediated by three different types of tachykinin receptor, termed NK1, NK2 and NK3 receptors, while the gastro-intestinal actions of CGRP are brought about by CGRP1 and possibly other CGRP receptors. These neuropeptide transmitters are expressed by enteric neurons, intestinal muscle, epithelium and vascular system in a cell-specific manner and enable SP, NKA and CGRP to influence motility, electrolyte and fluid secretion, vascular and immune functions in a peptide- and region-specific fashion. Inflammatory disorders of various aetiology involve changes in the peptidergic innervation of the gut, and inflammatory bowel disease is associated with NK1 receptor upregulation in intestinal blood vessels and lymphoid structures. Some of these alterations are reproduced in experimental models of gastro-intestinal disease, and there is mounting evidence that an imbalanced function of peptidergic neurons contributes to motor, secretory, vascular and immunological disturbances in intestinal anaphylaxis, infection and inflammation. In a therapeutic perspective it seems conceivable that tachykinin and CGRP receptors antagonists can be employed as spasmolytic, antidiarrhoeal, anti-inflammatory and antinociceptive drugs.
Effects of Daily Fat or Ethanol Ingestion on the Cholecystokinin- Pancreas and the Gastrin- Enterochromaffin-Like Cell Axes in Rats
Authors: Yamada Hironori , Kimura Keizo , Chen Duan
Published: April 2003

Background/Aims: Ingestion of fat and ethanol is thought to contribute to the development of pancreatitis through the release of gut hormones, such as cholecystokinin (CCK) and gastrin. We have examined the effects of fat or ethanol on the relationships between CCK and pancreas on one hand and between gastrin and the enterochromaffin-like (ECL) cells in the stomach on the other. Methods: In one study, rats received 2 ml of medium-chain triglycerides or water twice a day by the oral route for 12 days. In another study, rats received 2.5, 5, 10 or 20% ethanol in drinking water for 12 days. All rats were killed on day 13. Results: There were no changes in either the plasma CCK concentration or the pancreatic weight and DNA content in the fat-fed rats. The serum gastrin concentration and the histidine decarboxylase (HDC) activity, HDC mRNA level and histamine content of the ECL cells were lower in fat-fed rats than in control rats. Ethanol did not affect either the plasma CCK concentration or the pancreatic weight and DNA content. The serum gastrin concentration was reduced in the rats that received 5, 10 or 20% ethanol. Also the HDC activity and histamine content of the ECL cells were reduced in the rats that received 10 and 20% ethanol. Conclusion: Daily ingestion of fat or ethanol for 12 days was without effects on the plasma CCK concentration and the pancreas, but reduced the serum gastrin concentration and the activity of the ECL cells in the rat.
Diet Supplemented with Yoghurt or Milk Fermented by Lactobacillus casei DN-114 001 Stimulates Growth and Brush-Border Enzyme Activities in Mouse Small Intestine
Authors: Thoreux Karine , Balas Daniel , Bouley Christine , Senegas-Balas Françoise
Published: April 2003

The nutritional benefits of lactic acid bacteria in fermented dairy products have been well documented, especially in terms of weight gain and feed efficiency, but not in terms of small intestine adaptation. The effects of a diet supplemented (30% wt/wt) with milk fermented either by Lactobacillus casei DN-114 001 or yoghurt for 3 or 15 days were investigated in the small intestine of mice by morphometry, kinetic analysis and determination of brush-border enzyme activities. Results were compared with those obtained with standard or milk isocaloric diets. Cell proliferation and villous area were significantly increased in the proximal intestine of mice fed the fermented-milk-supplemented diets for 3 days and were associated with hypertrophy and hyperplasia of Paneth and goblet cells. Lactase-specific activity was increased by fermented-milk diets at days 3 and 15, whereas there was no variation in maltase-specific activity. Alkaline phosphatase-specific activity was increased after 3 days of the three tested diets in the whole intestine, and after 15 days in the proximal intestine. Aminopeptidase activity was increased in the distal part of the intestine after 3 days of the 3 diets. Our findings suggest that diets supplemented with fermented milks have a positive effect on the trophicity of the mucosa in the small intestine of mice.
Clinical Significance of Arterial Ketone Body Ratio in Chronic Liver Disease
Authors: Yamaoka Kazuaki , Kanayama Masaaki , Tajiri Kazuo , Yamane Michio , Marumo Fumiaki , Sato Chifumi
Published: April 2003

Background: Arterial ketone body ratio (acetoacetate/3-hydroxybutyrate, AKBR) has been reported to be a useful tool for the estimation of liver functional reserve, but a more recent report has cast doubt on the clinical significance of this redox theory. Furthermore, the effect of a diminution of liver functional reserve on AKBR has not been documented in chronic liver disease. Methods: AKBR was measured in normal control subjects (n = 10), heavy alcohol drinkers (n = 19), patients with chronic hepatitis (n = 18) and patients with liver cirrhosis (n = 25). Results: Though AKBR was lower in heavy alcohol drinkers (1.66 ± 0.82) than in the other noncirrhotic groups (1.97 ± 0.93 in normal control subjects, 2.25 ± 1.11 in patients with chronic hepatitis), this discrepancy did not reach a level of significance. AKBR in patients with liver cirrhosis (1.18 ± 0.52) was significantly lower than that in normal controls (p < 0.01). AKBR in Child’s class A, Child’s class B, and Child’s class C was 1.20 ± 0.60, 1.07 ± 0.56, and 1.27 ± 0.45, respectively, and there were no significant differences among them. Conclusion: AKBR may be parallel to liver mitochondrial redox potential and hepatic functional reserve to some extent, but it does not appear to be an accurate parameter for their estimation.
Budesonide in the Treatment of Collagenous Colitis
Authors: Delarive Joakim , Saraga Emilia , Dorta Gian , Blum André
Published: April 2003

Collagenous colitis is characterized by watery diarrhea and inflammatory infiltration associated with a subepithelial collagen deposit on colonic biopsies despite a normal or subnormal endoscopic appearance. We here describe 5 patients treated with the locally active steroid budesonide. Complete and partial response was observed in 3 and 2 patients, respectively. Budesonide thus seems to be of therapeutic benefit in collagenous colitis. Prospective randomized long-term studies are needed to support this hypothesis.
Endoscopic Ultrasonography
Authors: Caletti Giancarlo , Fusaroli Pietro , Bocus Paolo
Published: April 2003

Endoscopic ultrasonography (EUS) is nowadays a clinically relevant technology and its findings can have a major impact on patient management. This technique is currently indicated for staging digestive cancers, assessment of submucosal tumors, diagnosis of intestinal wall infiltrative diseases, common bile-duct stones and gut neuroendocrine tumors. As far as neoplasms are concerned, EUS appears to be a reliable and safe technique, thus making the physician able to plan either an aggressive surgical treatment, or a conservative palliative therapy. This is of the utmost importance in order to optimize medical-related costs, and to make the best therapeutic decision for each individual patient. EUS is also helpful in monitoring the course of a disease, as it is simple and virtually without complications. When EUS findings are not sufficient for a complete diagnosis, it is now possible to perform an EUS-guided fine-needle biopsy, which can allow a cytological diagnosis. Finally, some therapeutic endosonography-guided procedures are being increasingly adopted, such as cystoenterostomy, celiac plexus neurolysis, cholangio-pancreatography and selective injection of botulinum toxin in the muscle layer of the lower esophageal sphincter.