bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic Fungal Infections in Patients with Hematologic Malignancies: Indications and Limitations of the Antifungal Armamentarium
Authors: Böhme Angelika , Karthaus Meinolf
Published: April 2003

The rates of fungal infections have increased substantially in Europe as well as in North America. Most frequently Aspergillus spp. and Candida spp. are isolated. Despite the recent introduction of new azoles and lipid-based formulations of amphotericin B, there are relatively few randomized, controlled studies on the use of antifungal drugs in patients with hematological malignancies and invasive fungal infections. Conventional amphotericin B is considered the gold standard for the treatment of invasive fungal infections; however, adverse events limit conventional amphotericin B treatment. The newer azoles, fluconazole and itraconazole, are well tolerated; however, fluconazole has no activity against Aspergillus spp. An additional serious problem is the emerging resistance of nonalbicans Candida spp. to fluconazole. In this situation, lipid formulations of amphotericin B seem to be attractive, since the use of these drugs has been shown to be safe and effective. Considerably higher medical costs limit broader application of lipid formulations of amphotericin B. Because of the rapidly increasing incidence of serious fungal infections, we have reviewed current strategies and the role of newer antifungal drugs for the treatment of deep-organ infections.
A Comparative Study of Cefepime versus Ceftazidime as Empiric Therapy of Febrile Episodes in Neutropenic Patients
Authors: Wang Fu-Der , Liu Cheng-Yi , Hsu Hui-Chi , Gau Jyh-Pyng , Chau Wing-Keung , Haung Ming-Lih , Ho Chao-Hung
Published: April 2003

An open-label, randomized comparative study was conducted to evaluate the efficacy and safety of cefepime (2.0 g q. 8 h) and ceftazidime (2.0 g q. 8 h) in the empiric therapy of febrile neutropenic patients. A total of 45 eligible febrile episodes were randomized (1:1) to be treated with the study regimen. Nineteen febrile episodes treated with cefepime and 22 febrile episodes treated with ceftazidime were evaluable for efficacy. The two groups were comparable in terms of age, sex, height, weight, underlying neoplasm, number of pretherapy neutrophil, duration of neutropenia and types of infections. The overall therapeutic success rate of the cefepime group (53%) was comparable to the ceftazidime group (50%). It did not differ significantly (95% confidence interval: –0.28 to 0.34, p = 0.85). Eighty-eight percent of pathogens in each group were bacteriologically eradicated. The safety profile was similar in both groups. No patients in either group discontinued the therapy because of adverse events. None (0%) of the cefepime patients and 2 (9%) of the ceftazidime patients died of infection. The results of this study suggest that cefepime is an effective and safe agent in the empiric therapy of febrile episodes in neutropenic patients.
A Prospective, Randomised Comparison of Single- vs. Multiple-Dose Antibiotic Prophylaxis in Penetrating Trauma
Authors: Schmidt-Matthiesen Andreas , Röding Hans , Windolf Joachim , Sommerfeldt Dirk , Gutt Carsten , Pannike Alfred , Encke Albrecht
Published: April 2003

This study was designed to compare the clinical efficacy of a single dose of ceftriaxone with cefoxitin given 3 times a day for 3 days. Methods: Patients had to have a penetrating injury to only one part of the body, reach the hospital within 2 h and be operated on within 16 h after the trauma. Patients were excluded if it appeared likely that they would require mechanical ventilation for more than 24 h. The same applies to open or grade II/III craniocerebral trauma. The end point was the occurrence of infections within 10 days. The costs of antibiotic treatment were also calculated. Results: 96% of the ceftriaxone patients (n = 97) and 95% of the cefoxitin group (n = 98) remained infection-free. In neither treatment group was deep infection, abscess, phlegmon or sepsis seen. No additional surgery or intensive care due to infection was required. At $41.83 vs. $172.16, the average total cost of delivering antibiotic treatment was significantly lower in the ceftriaxone group (p < 0.001). Conclusion: Prophylaxis in penetrating trauma with a single dose of ceftriaxone is safe and has considerable practical and economic advantages.
Yuehchukene, a Bis-Indole Alkaloid, and Cyclophosphamide Are Active in Breast Cancer in vitro
Authors: Leung T.W.T. , Cheng G. , Chui C.H. , Ho S.K.W. , Lau F.Y. , Tjong J.K.J. , Poon T.C.C. , Tang J.C.O. , Tse W.C.P. , Cheng K.F. , Kong Y.C.
Published: April 2003

Yuehchukene (YCK) is a novel bis-indole alkaloid with weak estrogenic activity. Biochemical studies showed that YCK could attenuate estrogenic action. In this study, the response of MCF-7, an estrogen-receptor-positive breast cancer cell line, under different combinations of estradiol, cyclophosphamide and YCK, was tested. From the dose-response curve, we discovered that 10–2 M cyclophosphamide, even in its so-called ‘bio-inert’ form, could inhibit MCF-7 cell growth. However, the cytotoxic effect of cyclophosphamide was lost by reducing its concentration to ∼1 × 10–3 M. On the other hand, a low concentration (∼10–8–10–9 M) of YCK was found to potentiate the cytotoxic effect of cyclophosphamide on the MCF-7 cell line. Such an effect was absent in the estrogen-receptor-negative cell line MDA-MB-231. These findings, together with the dual role of a mixed estrogen and anti-estrogen effect, suggested that YCK and cyclophosphamide can be a potential combination in chemo-hormonal therapy for breast cancer.
Effect of Navelbine on Inhibition of Tumor Growth, Cellular Differentiation and Estrogen Receptor Status on Lewis Lung Carcinoma
Authors: Papageorgiou A. , Stravoravdi P. , Sahpazidou D. , Natsis K. , Chrysogelou E. , Toliou T.
Published: April 2003

We studied the antitumor activity of Navelbine (NVB) together with its ability to induce cellular differentiation and to influence estrogen receptor status of Lewis lung carcinoma (LLC). A total of 32 C57B1 mice divided into 5 groups were used for transplantation of LLC. Four groups of mice were treated with 5.0, 2.5 and 1.25 mg/kg/day from day 1 to 9 and 1.25 mg/kg on days 1, 7 and 13. Eight mice were controls. The dose of 1.25 mg/kg/day was the most effective and produced 72.7% inhibition of tumor growth. Ultrastructurally, on day 1 the cells showed poor differentiation. On day 14, in the case of 72.7% inhibition of tumor growth the study revealed a significant restoration of the morphology of the cells. Estrogen receptors gave a positive value in contrast to the initial measurement which was negative. The present study demonstrated good antitumor activity of NVB on LLC. NVB may also induce cellular differentiation and influence the estrogen receptor status.
Current Status and Fluconazole Treatment of Pelvic Fungal Gynecological Infections
Authors: Mikamo Hiroshige , Sato Yasumasa , Hayasaki Yoh , Tamaya Teruhiko
Published: April 2003

The incidence of opportunistic fungal infections has recently been increasing in many clinical fields. Fluconazole is commonly used against systemic fungal infections. The present study was undertaken to investigate the current status and the efficacy of fluconazole in pelvic fungal gynecological infections. Thirty-eight patients aged 36–72 years old diagnosed with pelvic peritonitis with positive fungal culture in pelvic ascites were enrolled in this study and given fluconazole treatment. Forty-two pathogens were isolated from the 38 assessable patients. The predominant pathogen was Candida albicans with an incidence of 61.9% (26/42). Others included non-albicans Candida species amounting to 38.1% (16/42): 19.0% (8/42) Candida glabrata, 7.1% (3/42) Candida tropicalis, 7.1% (3/42) Candida parapsilosis and 4.8% (2/42) Candida krusei. The clinical cure rate at the end of fluconazole treatment was assessed as 30/38 (78.9%), and the fungal eradication rate as 26/42 (61.9%). Each rate was 29/38 (76.3%) and 26/42 (61.9%), respectively, at 1 week after the treatment, while the eradication rate of C. albicans and non-albicans species was 20/26 (76.9%) and 6/16 (37.5%), respectively. There was no adverse effect exept for slight elevations of GOT, GPT and LDH observed in 1 patient (2.6%), which returned to normal after the treatment. It seems there may be an increasing trend of non-albicans species in pelvic fungal gynecological infection, against which fluconazole appears to be rather effective.
Surveillance of Nosocomial Cross-Infections due to Three Acinetobacter Genospecies (Acinetobacter baumannii, Genospecies 3and Genospecies 13) during a 10-YearObservation Period: Serotyping,Macrorestriction Analysis of GenomicDNA and Antibiotic Susceptibilities
Authors: Traub Walter H. , Bauer Dierk
Published: April 2003

During a 10-year surveillance period, a total of 2,359 isolates comprising the genus Acinetobacter were recovered and identified presumptively with phenotypic tests. Genospecies 3 was the most common (n = 1,053), followed by genospecies 13 (n = 352), Acinetobacter baumannii (n = 335), Acinetobacter lwoffi (n = 162), and genospecies 14 (n = 97); 100 isolates (4.2%) were categorized as questionable Acinetobacter. There were 34 clusters of putative nosocomial cross-infection due either to genospecies 3 (n = 16), A. baumannii (n = 10) or genospecies 13 (n = 8). Apart from 3 clusters due to two multiple-antibiotic-resistant strains of genospecies 13 and one strain of A. baumannii, respectively, there was no significant increase of antibiotic resistance discernible during the decade-long period of Acinetobacter surveillance.
Time-Kill Studies of Antimicrobial Combinations Including Cefotaxime, Ceftriaxone, Vancomycin and Meropenem against Cephalosporin-Resistant Streptococcus pneumoniae
Authors: Kim Baek-Nam , Woo Jun-Hee , Kim Yang-Su , Ryu Jiso , Kim Mi-Na , Pai Chik Hyun
Published: April 2003

Background: Resistance of Streptococcus pneumoniae to penicillin is now widespread and rapidly increasing all over the world. This has led to the critical need for alternative antimicrobial therapy. Methods: To assess the activities of antimicrobial combinations, including cefotaxime, ceftriaxone, vancomycin and meropenem, time-kill studies were conducted against five strains of penicillin- and cephalosporin-resistant S. pneumoniae at clinically achievable antimicrobial concentrations in cerebrospinal fluid. Results: Combinations of an extended-spectrum cephalosporin with vancomycin were not synergistic. Meropenem had a comparable bactericidal activity to those combinations, and its killing activity was not affected by the addition of cefotaxime, ceftriaxone or vancomycin. Conclusions: It is suggested that meropenem could be an effective alternative for the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis. However, more clinical data are required before it can be recommended as an effective antimicrobial agent for such cases.
In vitro Activity of Moxifloxacin(BAY 12-8039) against Respiratory Tract Pathogens from Six Latin-American Countries
Authors: Cardeñosa G. Oscar , Soto-Hernández José Luis
Published: April 2003

The in vitro antibacterial activity of moxifloxacin (BAY 12-8039) was evaluated against 636 isolates of respiratory tract pathogens. The isolates were collected from July 1997 to August 1998 in the frame of a multinational Latin American study. E-test strips calibrated to read moxifloxacin MIC ranges from 0.002 to 32 μg/ml were used in susceptibility testing. Weekly quality control tests in each laboratory ensured reproducibility. Laboratories from Argentina, Brazil, Chile, Colombia, Mexico and Uruguay participated. MIC90 for moxifloxacin were as follows: Streptococcus pneumoniae (304 isolates) 0.25 μg/ml, Haemophilus influenzae (135 isolates) 0.125 μg/ ml, Streptococcus pyogenes (66 isolates) 0.25 μg/ml, Moraxella catarrhalis (62 isolates) 0.25 μg/ml and methicillin-sensitive Staphylococcus aureus (69 isolates) 0.25 μg/ml. These results agreed with reports from other areas. Moxifloxacin showed excellent activity against respiratory pathogens from participant countries.
Comparison of the Bactericidal Activity of Trovafloxacin and Ciprofloxacin, Alone and in Combination with Cefepime, against Pseudomonas aeruginosa
Authors: McNabb JoCarol , Quintiliani Richard , Nightingale Charles H. , Nicolau David P.
Published: April 2003

Background: Although ciprofloxacin exhibits more intense microbiological activity against Pseudomonas aeruginosa than does trovafloxacin, the clinical relevance of this observation remains questionable, particularly when the agents are combined with another antipseudomonal agent. Methods: To evaluate this further, we conducted a four-way crossover trial to compare the bactericidal activities of ciprofloxacin and trovafloxacin, alone and in combination with cefepime, against three clinical isolates of P. aeruginosa. Healthy subjects received the following regimens, dosed to steady state: trovafloxacin 300 mg/24 h; ciprofloxacin 400 mg/12 h; trovafloxacin 300 mg/24 h plus cefepime 2 g/12 h, and ciprofloxacin 400 mg/12 h plus cefepime 2 g/12 h. Serum bactericidal titers were performed with each regimen. Results: As monotherapy, the area under the bactericidal curve for ciprofloxacin exceeded that of trovafloxacin for all isolates. No significant difference in the overall degree of bactericidal activity was noted for two of three P. aeruginosa isolates for the combination regimens. Additionally, both combination regimens provided bactericidal activity for 100% of the dosing interval for all isolates. Conclusion: These results indicate that, while in vitro differences exist among these quinolones for P. aeruginosa, when a fluoroquinolone is combined with a β-lactam, this is likely to be of little clinical significance.
Indomethacin Inhibits the Accumulation of Tumor Cells in Mouse Lungs and Subsequent Growth of Lung Metastases
Authors: Levin Galit , Kariv Na’am , Khomiak Elena , Raz Amiram
Published: April 2003

Background: The interaction of cancer cells with blood cells and cell wall components evokes inflammatory responses and is a critical event in the metastatic process. Indomethacin is a potent inhibitor of the cyclooxygenase (COX) enzymes and has previously been shown to decrease the growth of primary tumors in vivo. Proinflammatory prostaglandins produced by the two COX enzymes may also play a role in the development of metastases. Methods: To directly address this question, we tested the effect of indomethacin on the accumulation of circulating [3H]-uridine-labeled tumor cells in the lungs and on the subsequent development of lung tumors. Results: We found that inhibition of COX activity in the recipient mice prior to the injection of tumor cells decreased the percentage of the cells arrested in the lungs. This effect was highly significant since it subsequently led to substantial attenuation of lung metastasis development. Conclusion: These data thus demonstrate the antimetastatic effect of indomethacin through a mechanism which involves a reduction in tumor cell uptake by the lungs.
Endoluminal Instillation of Bisacodyl inPatients with Severe (Slow Transit Type)Constipation Is Useful to Test Residual ColonicPropulsive Activity
Authors: Bassotti Gabrio , Chiarioni Giuseppe , Germani Ugo , Battaglia Edda , Vantini Italo , Morelli Antonio
Published: April 2003

Background: Chronic constipation is a frequent symptom among the general population, and a minority of cases do not respond to any therapeutic measures, except surgery. The purpose of this study was to test the residual colonic motor propulsive activity with a pharmacologic stimulus in a series of patients referred for severe constipation. Patients: Twenty-five chronically constipated patients, slow transit type, age range 16–71 years, unresponsive to conventional medical treatment and referred for functional evaluation, entered the study. Methods: Colonic manometry by means of an endoscopically positioned probe was carried out in all patients. Following a basal recording period, a placebo solution followed by 10 mg bisacodyl solution was infused into the colon through the more proximal recording port. Results: After bisacodyl infusion, about 90% of patients showed a motor response characterized by the appearance (within on average 13 ± 3 min) of one or more high-amplitude propagated contractions, the manometric equivalent of mass movements, and about 75% of these were followed (mean 18.5 ± 4 min) by defecation. Conclusions: Physiological and pharmacological testing of colonic motor activity may be important in severely constipated patients, especially in those labeled as ‘intractable’, in whom more in depth investigation planning may encourage further therapeutic efforts.
Helicobacter pylori in the Oral Cavity Reflects Handling of Contaminants but Not Gastric Infection
Authors: Doré-Davin C. , Heitz M. , Yang H. , Herranz M. , Blum A.L. , Corthésy-Theulaz I.
Published: April 2003

Helicobacter pylori colonises the gastric mucosa, but can also be found within the oral cavity. The presence of H. pylori was monitored in the oral cavity of 22 patients with duodenal ulcer, before and after antibiotic treatment and of 24 hospital employees who were or were not professionally exposed to H. pylori. Gastric infection was determined by breath test. Bacteria in the oral cavity were detected by nested PCR of samples containing saliva and dental plaque, using primers specific for 16S rRNA and ureC genes. Before treatment, 9 out of 22 infected ulcer patients harbored H. pylori in their oral cavity. Bacteria disappeared from the oral cavity of 3 of 7 cured patients. Twelve of 17 exposed subjects harbored H. pylori in their oral cavity, while no bacteria could be detected in the mouths of the 7 nonexposed subjects. Presence of bacteria in the oral cavity reflects handling of contaminants; it does not correlate with gastric infection and does not seem to promote it.
Febrile Convulsions in 220 Children – Neurological Sequelae at 12 Years Follow-Up
Authors: MacDonald Bridget K. , Johnson Anthony L. , Sander Josemir W.A.S. , Shorvon Simon D.
Published: April 2003

We report a 12-year follow-up study of children with febrile convulsions (FCs). The National General Practice Study of Epilepsy (NGPSE) is a large prospective community-based cohort study of 1,195 patients of all ages from first presentation with an identified seizure. Two hundred and twenty children with a first febrile convulsion were identified from the above study between 1984 and 1987. Children were prospectively followed up to ascertain subsequent seizures, neurological problems and treatment. Two hundred and seven patients were followed for a minimum of 8.4 years (median 11.2 years). In the FC cohort, 6% of the children developed subsequent epilepsy, which compares with a population risk of about 1.4%. Ten percent had neurological sequelae. Eleven percent of the children had received medication to prevent recurrence of FC, and in one third of these cases, this was for simple FCs. Using a time-dependent covariate Cox proportional hazards model, the number of FCs was associated with an increased risk of epilepsy (hazard ratio 2.48; 95% confidence limits, CL 1.68, 3.65) up to a limit of 4. A statistically significant association between occurrence of complex FC and subsequent epilepsy was not found, but a review of other studies quantified the odds ratio for epilepsy after a complex first FC as 3.4 (95% CL 2.1, 5.4). Epilepsy is a significant if infrequent sequel to FCs. Factors associated with subsequent epilepsy are the number of FCs or a complex first FC. Overtreatment of this condition continues.
Detection of Human Herpesvirus 6 Variant A in Peripheral Blood Mononuclear Cells from Multiple Sclerosis Patients
Authors: Kim Joong-Seok , Lee Kwang-Soo , Park Ji-Hyun , Kim Mi-Young , Shin Wan-Sik
Published: April 2003

Several authors report that human herpesvirus 6 (HHV-6) variants have different epidemiologies, in vivo tropism and pathogenic potentials. However, it is not well known what pathogenic roles its neurotropism might have in the variant type. As some active plaques of multiple sclerosis (MS) brain tissue harbor HHV-6 DNA divergent from the prototype virus, the possibility that the variant strain may play a role in the pathogenesis of MS has been suggested. Therefore, we tried to investigate the role of HHV-6 variants in the pathogenesis of MS. As HHV-6 is predominantly a T-cell-tropic virus, we examined HHV-6 DNA sequences in peripheral blood mononuclear cells (PBMC) from 34 MS patients, 6 with idiopathic transverse myelitis, 2 with optic neuritis and 20 healthy controls. Nested polymerase chain reaction was used to detect the HHV-6 genome. To discern HHV-6 variants A and B, amplification products were digested by restriction enzyme. We found that 7 of 34 MS patients and 2 of 6 patients with idiopathic transverse myelitis had the HHV-6 genome. On the contrary, there was no HHV-6 genome in the control group. All genomic sequences were of HHV-6 variant A (HHV-6A). Our results suggest that the detection of HHV-6A in the PBMC of patients with MS may raise the possibility of a relationship between latent HHV-6A infection and the pathogenesis of MS.
Primary Intracerebral Hemorrhages in the Besançon Stroke Registry
Authors: Tatu Laurent , Moulin Thierry , El Mohamad Rachid , Vuillier Fabrice , Rumbach Lucien , Czorny Alain
Published: April 2003

The purpose of this study was to estimate the risk factors, early course, outcome and neuroimaging patterns in primary intracerebral hemorrhages (PIH). Using the Besançon Stroke Registry, 350 patients with first PIH documented by computed tomography (CT) between 1987 and 1993 were included in the present study. Patients with hemorrhage secondary to traumatism, brain tumor, thrombolytic treatment, vascular malformation or with hemorrhagic infarction were excluded. All CTs were evaluated to define the location, extension and volume of bleeding (55% of CT were performed within the first 12 h). Causes of death were classified and the 30-day outcome survival was evaluated with a modified Rankin scale (40 patients underwent a noncodified surgical procedure and were excluded from the outcome evaluation). Locations were lobar (36.5%), lenticular (32%), thalamic (15.7%), cerebellar (8.8%), midbrain and pons (2%), intraventricular (2%), caudate (1%) and multiple (2%). Risk factors included hypertension (54.8%), alcohol (18%) anticoagulant treatment (8.8%) and none (31.2%). The largest mean volume was in putaminal (41.7 ml) and lobar (39.8 ml) locations. Among 191 patients admitted before the 12th hour of evolution, 51 (26.7%) experienced an early clinical worsening. In this group, the percentage of patients with anticoagulant treatment (19.6%) was significantly higher (p < 0.0001). PIH enlargement was documented in 3 patients. Overall, the 30-day mortality rate was 24.2% with 48% of all deaths occurring in the first 3 days. Death and 30-day survival status were closely associated with PIH volume (p < 0.0001). Our study provides information on the natural history of PIH and especially on initial evolution. PIH volume seems to be an interesting indicator for death and functional status at 30 days.
Relationship between Ischemia and Neuropathy
Authors: Teunissen L.L. , Notermans N.C. , Wokke J.H.J.
Published: April 2003

To evaluate what at present is known about the relationship between vascular diseases and the development of chronic polyneuropathy, the literature on ischemia and peripheral nerve damage was reviewed with emphasis on chronic ischemia.
Collagen Secretion by Human Gastric and Skin Fibroblasts: Implications for Ulcer Healing
Authors: Lanas A. , García-Gonzalez A. , Esteva F. , Piazuelo E. , Jimenez P. , Morandeira J.R.
Published: April 2003

Fibroblasts (FIB) play an important role in the wound-healing process. It is not known whether human skin and gastric FIB show different responses to regulatory compounds. In this study, we have examined the collagen production by these FIB after different stimuli. In vitro release of collagen into the medium by steady-state confluent human FIB cultures was assessed over a 24-hour period by 3H-proline incorporation into collageneous protein. Serum and epidermal growth factor increased collagen secretion in both types of FIB, but gastric FIB produced less collagen than skin FIB. Prostaglandin E1 inhibited collagen production in both types of FIB, but nonsteroidal anti-inflammatory drugs and interleukin-1β, a cytokine involved in the wound-healing process, had opposite effects on gastric and skin FIB. The effects of lipoxygenase metabolites on collagen secretion was small, but different in both types of FIB. We conclude that, when compared to skin FIB, human gastric FIB produce less collagen and show pronounced different responses to different agents, which might be relevant to explain (in part) their clinical effects on ulcer healing. These data provide new insights into the wound-healing process.
Autoantibodies against Cardiolipin in the Serum of Patients with Colorectal Adenocarcinoma:Their Prognostic Significance
Authors: Syrigos K.N. , Charalampopoulos A. , Konstantoulakis M.M. , Karayiannakis A. , Tsibloulis V. , Peveretos P.
Published: April 2003

Using an ELISA method, the sera of 43 patients with colon adenocarcinoma (CA) and of 26 surgical patients with nonmalignant disease of the gastrointestinal tract were studied for the presence of autoantibodies against cardiolipin (CLP) before and 1 month after surgery. Forty healthy volunteers were used as controls. Fourteen CA patients were found to be positive for anti-CLP autoantibodies before surgical treatment, and 15 patients were found to be positive 1 month after surgery. The difference between the group of CA patients and either the group of patients with nonmalignant diseases of the GI tract, or the group of healthy individuals was statistically significant (p = 0.003). The group of CA patients with high anti-CLP serum titer had a better outcome compared with the group of patients without detectable autoantibody titer (p = 0.08), estimated based on the frequency of recurrences, during the follow-up period. Further studies are in progress to evaluate the significance of anti-CLP antibodies as a biological marker of prognosis in CA patients.
2-Chlorodeoxyadenosine (Cladribine) in Combination with Low-Dose Cyclosporin Prevents Rejection after Allogeneic Heart and Liver Transplantation in the Rat
Authors: Schmid T. , Hechenleitner P. , Mark W. , Fischer M. , Roberts K. , Geisen F. , Klima G. , Dietze O. , Konwalinka G. , Margreiter R.
Published: April 2003

The purine analogue 2-chlorodeoxyadenosine (2-CDA) has been shown to possess synergistic immunosuppressive properties when given together with cyclosporin (CSA) in a rat small bowel transplant model. The present study investigated the immunosuppressive potency of 2-CDA alone and in combination after liver or heart transplantation in a fully allogeneic rat model with 5 animals in each group. Immunosuppression was provided with CSA 10 mg/kg body weight (BW)/day orally or 2-CDA 0.1 mg/kg/BW day intravenously or both compounds together in the dosages mentioned. Animals were sacrificed on day 10 following transplantation, and graft histology was assessed. In addition, cardiac graft function was evaluated by palpation immediately prior to sacrificing the animal. CSA given alone was able to mitigate but not prevent rejection. 2-CDA alone did not exhibit any detectable immunosuppressive effect. When CSA was combined with 2-CDA, no rejection was seen in 80% of the liver allografts and in 60% of heart allografts, and only mild rejection was observed in the remaining animals. All hearts of the combined treatment group, however, beat strongly. From these findings it is concluded that 2-CDA alone has no, but together with CSA a strong immunosuppressive effect in preventing solid organ allograft rejection.
Treatment with Growth Hormone and Insulin-Like Growth Factor-1 in Septicemia: Effects on Carbohydrate Metabolism
Authors: Balteskard Lise , Unneberg K. , Mjaaland Marianne , Sager G. , Jenssen T.G. , Revhaug A.
Published: April 2003

Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may be beneficial against the protein catabolism seen in injury and septicemia. Further understanding of their effects on carbohydrate metabolism is needed. In a septic porcine model receiving total parenteral nutrition, pretreatment with GH or IGF-1 (or no treatment in controls) was followed by an infusion of live Escherichia coli bacteria. Endogenous glucose production, carbohydrate oxidation, glucose and lactate fluxes over the liver, gastrointestinal organs, kidney, and hindleg were determined. Endogenous glucose production increased during septicemia in the GH group. The metabolic acidosis induced by septicemia was augmented by GH, but attenuated by IGF-1. The alanine and lactate levels were significantly higher in the GH- than in the IGF-1-treated animals during septicemia. IGF-1 pretreatment appeared to induce favorable effects while GH pretreatment might produce unfavorable effects on carbohydrate metabolism in septic piglets.
Laser Doppler Evaluation of Microcirculation Behaviour during an Ischaemia-Reperfusion Injury
Authors: Rocca M. , Giavaresi G. , Fini M. , Orienti L. , Giardino R.
Published: April 2003

Laser Doppler flowmetry (LDF) was tested in an experimental ischaemic model on rat limbs to evaluate the degree of ischaemia and to find a possible correlation with values obtained with this device and prognosis. Under general anaesthesia, 40 Wistar rats were submitted to 4 h and 30 min of ischaemia of the left hind limb. Ten rats formed the control group (group 1). Two enzymes, native superoxide dismutase (SOD) and SOD modified with polyethylene glycol, were employed in 15 rats each (groups 2 and 3). Data were collected by means of LDF both in the sole and muscles before ischaemia (steady state), during ischaemia and at the beginning of reperfusion, and only in the sole after 1 h of reperfusion. A range of predictive (95%) perfusion values (PU) for limb healing or necrosis was identified at the beginning of reperfusion. During ischaemia, PU changed from 0 to 10, both in the sole and in the muscle. A three-factor ANOVA (site, group, time) did not show interaction of these factors with PU (F = 1.655; p = 0.195), even if every single effect was significant (p < 0.0005). A two-factor ANOVA (group, time) showed a significant interaction of these factors with PU (F = 4.079; p = 0.019). The logistic regression between the reperfusion PU of each site and the survival of the limb was observed at the beginning and after 1 h of reperfusion in the sole only. Furthermore, a correlation between sole and muscle PU at the steady state and at the beginning of the reperfusion period was observed. The results showed the effectiveness of LDF, which can be considered a quite reliable tool to evaluate the degree of ischaemia and to have a good correlation with prognosis in this kind of experiments.
Cellular Signal Level of Cyclic AMP and Functional Integrity of the Small Bowel after Ischemic Preservation: An Experimental Pilot Study in the Rat
Authors: Minor T. , Isselhard W.
Published: April 2003

The intestinal mucosa is one of the tissues most sensitive to ischemia. Anoxia of the gut is known to result in an early impairment of cellular permeability and transcapillary barrier function upon reperfusion. In vitro, an increased permeability of endothelial cell monolayers could be shown to be related to a decrese in cellular content of cyclic AMP (cAMP). Thus, the present study was aimed at investigating the role of the cellular cAMP second messenger signal in the context of intestinal ischemia/reperfusion injury after cold preservation. Segments of the upper jejunum were isolated from Wistar rats with vascular pedicle and flushed with 10 ml of UW preservation solution. The intestinal lumen was rinsed with 10–15 ml of UW solution and the organ was stored immersed in UW solution at 4°C for 4 or 18 h. After 18 h of cold ischemic storage structural and functional integrity of the preparation was tested by perfusion via the vascular system with modified Krebs-Henseleit buffer and the intestinal lumen with saline solution (containing 200 mg % of galactose) for 30 min. In half of the experiments, dibutyryl-cAMP a membrane permeable cAMP analogue, was admixed to the flush solution (2 mM). It was found that tissue levels of cAMP linearily decreased to 34% during 18 h of ischemic preservation in UW. Addition of dibutyryl cAMP significantly improved postischemic recovery of the intestinal preparations by decreasing cellular loss of lactic dehydrogenase (18.2 ± 4.6 vs. 7.6 ± 2.6 U/I) and improving intestinal absorbtion of galactose from the luminal circuit (0.18 ± 0.14 vs. 0.36 ± 0.14 mg %) after 30 min of oxygenated reperfusion, but was not effective to reduce transcapillary water loss into the gut lumen. It is concluded that the anoxia-related decrease of the cellular cAMP level may represent a codeterminator influencing postischemic recovery of the small bowel and that the control of the cAMP signal of ischemic intestines might improve the quality of cold preservation of the gut prior to transplantation.
Bone Morphogenetic Protein in Bone Neoplasms: Comparison of Different Detection Methods
Authors: Laitinen Minna , Marttinen A. , Aho A.J. , Lindholm T.S.
Published: April 2003

The presence of bone morphogenetic proteins (BMPs) in 13 primary bone neoplasms was investigated with conventional bioassay method and immunohistochemically using antiserum against highly purified mixture of bovine BMPs as antibody. In conventional bioassay after implantation of lyophilized bone tumor tissues into mouse muscle pouches 9/13 samples turned out positive by radiography and 10/13 histologically. By immunohistochemical staining, using the avidin-biotin-peroxidase method, signs of BMPs could be verified in all cases investigated. Microscopical scoring showed the local concentration of BMPs to be especially high in sections from giant cell tumors when compared to other bone neoplasms.
Beneficial Effects of Verapamil on Intestinal Ischemia and Reperfusion Injury: Pretreatment versus Postischemic Treatment
Authors: Kimura M. , Kataoka M. , Kuwabara Y. , Sato A. , Kato T. , Narita K. , Okahira T. , Fujii Y.
Published: April 2003

We studied the effect of verapamil on intestinal ischemia and reperfusion (I/R) injury. Intestinal ischemia was induced by clamping the superior mesenteric artery for 30 min followed by reperfusion. Magnetic resonance spectroscopy was employed as a marker of the changes in the energy metabolism. Further, histological changes and the changes of water contents were evaluated. Recovery rates of energy metabolism after intestinal I/R were improved by verapamil, administered before and after ischemia, and tissue edema was significantly reduced with verapamil. These findings suggest that verapamil results in an improved recovery of the energy metabolism and cellular preservation, presumably by reducing the intracellular calcium influx.
Myocardial Hemodynamic and Metabolic Changes during Abdominal Insufflation with Carbon Dioxide
Authors: Katircioglu S.F. , Atalay F. , Keskin A. , Saritaş Z. , Bostanoglu S. , Yücel D. , Köse K.
Published: April 2003

It is a well-known fact that laparoscopic procedures performed with carbon dioxide insufflation impair myocardial function. In this study, we aimed to determine the safety limitations of various intra-abdominal pressure values during abdominal insufflation with carbon dioxide. Of the 24 mongrel dogs, 6 were assigned to one of four different pressure groups (10, 15, 20 and 30 mm Hg), respectively. Cardiac output, right/left heart pressures, and the first derivative of ventricular pressure were monitored. Myocardial oxygen consumption, myocardial lactate/oxygen extraction, tissue lactate and adenosine triphosphate levels were determined. Measurements were performed initially as a control, at 15-min intervals during 1 h of insufflation and 1 h after desufflation. At 10 mm Hg carbon dioxide pressure, hemodynamic and metabolic parameters were not significantly different. Cardiac output decreased significantly in the 20 and 30 mm Hg groups (p < 0.05: 10, 15 vs. 20, 30 mm Hg). Although cardiac output did not change at 15 mm Hg, the dp/dt value was significantly reduced. Cardiac output at the 60th min was 1,960 ± 75 ml/min in the 10 mm Hg group, 1,885 ± 40 ml/min in the 15 mm Hg group, 1,770 ± 45 ml/min in the 20 mm Hg group and 1,695 ± 40 ml/min in the 30 mm Hg group. Myocardial oxygen consumption was reduced at 15, 20 and 30 mm Hg (p < 0.05: 10 vs. 15, 20 and 30 mm Hg). In the myocardial tissue, ATP decreased from 19 ± 2 to 12 ± 1.2 µmol/g at 15 mm Hg, from 19 ± 1.9 to 9.4 ± 1.3 µmol/g at 20 mm Hg and from 18 ± 3.2 to 8.2 ± 1.9 µmol/g at 30 mm Hg. Changes in hemodynamic and metabolic parameters of the heart are reversible and may not lead to any significant impairments in patients having normal cardiopulmonary function, but pose a risk in patients with respiratory disease and limited myocardial reserve.
Comparison of the Solutions of Bretschneider, St. Thomas’ Hospital and the National Institutes of Health for Cardioplegic Protection during Moderate Hypothermic Arrest
Authors: Kober Ingeborg M. , Obermayr R.P. , Brüll T. , Ehsani N. , Schneider Barbara , Spieckermann P.G.
Published: April 2003

We evaluated three cardioplegic solutions, Bretschneider’s cardioplegic solution (HTK), St. Thomas’ Hospital solution (STH) and the solution of the National Institutes of Health (NIH), a solution with added nitroglycerin and lidocaine, for their ability to minimize ischemia-reperfusion injury in a working rat heart model. After cardioplegic arrest at 4°C and subsequent 45 min of ischemic storage at 25°C the function recovery of hearts was examined during 1 h of normothermic crystalloid reperfusion using Krebs-Henseleit buffer as perfusion medium. We noted a significantly better preservation of the maximum (+dp/dtmax) and minimum (–dp/dtmax) velocity of pressure development and a significantly higher coronary flow with the use of HTK (2,657 mm Hg/s, 2,122 mm Hg/s, 17 ml/min) compared to STH (1,600 mm Hg/s, p < 0.05; 1,591 mm Hg/s, p < 0.05; 11 ml/min, p < 0.05), and an intermediate level of preservation of hemodynamic parameters with NIH (2,149 mm Hg/s, 1,766 mm Hg/s, 12 ml/min). Concerning the cardiac output, however, no major difference was found between the HTK (41 ml/min), the STH (34 ml/min) and the NIH group (36 ml/min). The decay of the myocardial energy charge was significantly lower in both the HTK and the NIH group as compared with conservation in STH solution. Lactate was lowest in the HTK group, CK and LDH releases in the effusate remained lowest after HTK and NIH preservation. The data of this study suggest that HTK and NIH most perfectly reduce the impairment of myocardial function and provide better myocardial protection during ischemic arrest at 25°C and superior recovery compared to STH solution.
Healing of Colonic Anastomoses after Immediate and Delayed Administration of 5-Fluorouracil plus Folinic Acid
Authors: Kanellos I. , Kazantzidou D. , Evangelou I. , Galovatsea K. , Zaraboukas T. , Dadoukis I.
Published: April 2003

The purpose of this experimental study was to investigate whether the delayed, postoperative, intraperitoneal administration of 5-fluorouracil plus folinic acid had adverse effects on wound healing, as did their early administration. Seventy male Wistar rats underwent colonic resection followed by anastomosis of the colon. The animals were randomized into four groups. The rats in control group 1 received a 0.9% NaCl solution intraperitoneally and those in group 2 received 5-fluorouracil (20 mg/kg) plus folinic acid (2 mg/kg) immediately after surgery and for the next 3 days. The rats in control group 3 and those in group 4 received intraperitoneally a 0.9% NaCl solution or 5-fluorouracil plus folinic acid, respectively, from postoperative day 4 to day 7. The rats were sacrificed on the 8th postoperative day. The rupture rate of the anastomoses was statistically significantly higher in group 2 with early treatment compared to control group 1 (p < 0.05); no differences were observed between control group 3 and group 4 with delayed treatment (p > 0.05). Adhesion and abscess formation were more marked in group 2 compared to control group 1; no differences were recorded between groups 3 and 4. The anastomotic bursting pressure was statistically significantly lower in group 2 compared to control group 1 (p < 0.05); no differences were measured between groups 3 and 4. Histologic evaluation showed a more profound inflammatory response and less marked fibroblastic activity in group 2 compared to control group 1; new collagen production was more evident in group 1. No such differences were observed between groups 3 and 4. In conclusion, the immediate, postoperative, intraperitoneal administration of 5-fluorouracil plus folinic acid inhibited wound healing, but delaying chemotherapy (beginning on the 4th postoperative day) had no adverse effects on the healing of colonic anastomoses and can be considered safe.
Effect of Triiodothyronine Administration on the Recovery of Liver Oxidative Capacity after Partial Hepatectomy
Authors: Červinková Z. , Svátková R. , Kalous M. , Rauchová H. , Červinka M. , Drahota Z.
Published: April 2003

The aim of the present work was to investigate the role of triiodothyronine on liver regeneration after partial hepatectomy in the rat. During the first 3 days of liver regeneration, total protein, total DNA content and total cytochrome c oxidase activity of the residual tissue increased from 30% immediately after partial hepatectomy to 70% of the preoperative values in control rats. In triiodothyronine-treated rats, the increase in total protein was the same (70%), however, the increase in total liver DNA content and total cytochrome c oxidase acitivity was 100 and 135%, respectively during the first 3 days of regeneration. Triiodothyronine administration also increased significantly the activity of mitochondrial ATPase in regenerating liver.
Effect of Early versus Delayed Postoperative Injection of 5-Fluorouracil plus Interferon-Alpha on Colonic Healing
Authors: Kanellos I. , Odisseos C. , Kazantzidou D. , Galovatsea K. , Zaraboukas T. , Dadoukis I.
Published: April 2003

The purpose of this study was to determine whether delayed, postoperative, intraperitoneal treatment with 5-fluorouracil (5-FU) plus interferon-α-2a (IFN) has adverse effects on colonic healing, as does early treatment. Seventy male Wistar rats underwent colonic anastomoses. The rats were randomized to one of four groups. Early intraperitoneal injection was given to groups 1 and 2 which was repeated once daily for the first 3 postoperative days. Treatment was delayed in groups 3 and 4, from the 4th to the 7th postoperative day. A 0.9% NaCl solution was injected in the rats of control groups 1 and 3. In groups 2 and 4, we infused 5-FU (20 mg/kg/day) and IFN (45,000 IU/kg/day). All the animals were sacrificed on the 8th postoperative day. The anastomotic rupture rate was significantly higher in the rats of group 2 compared to control group 1 (p < 0.05), while there were no differences between groups 3 and 4 (p > 0.05). Abscess formation and adhesions were more frequent in group 2 compared to control group 1, while no differences were observed between groups 3 and 4. Anastomotic bursting pressure was statistically significantly lower in the rats of group 2 compared to group 1 (p < 0.05); no differences were noticed between groups 3 and 4 (p > 0.05). Simultaneous histologic evaluation showed a more profound inflammatory reaction and delayed anastomotic healing in group 2 compared to control group 1; there were, however, no differences between groups 3 and 4. In conclusion, the immediate, postoperative, intraperitoneal injection of 5-FU plus IFN impairs colonic healing while delayed treatment (starting on the 4th postoperative day) has no adverse effects on wound healing.
Central Hemodynamic Changes in Experimental Muscle Crush Injury in Pigs
Authors: Rawlins M. , Gullichsen E. , Kuttila K. , Peltola O. , Niinikoski J.
Published: April 2003

To investigate central and pulmonary hemodynamics in a standardized normovolemic experimental muscle injury model, 8 anesthetized and mechanically ventilated test pigs were intracavally infused with 100 ml of autologous muscle extract over a period of 100 min; 8 control pigs received Ringer’s solution. The cardiac index decreased 20% and the heart rate decreased 10% within 30 min of starting the infusion in the muscle extract group and remained depressed. Mean arterial pressure increased significantly in both groups. The pulmonary capillary wedge pressure and central venous pressure remained relatively unchanged during the 5-hour study. A 2-fold increase in mean pulmonary arterial pressure and a nearly 4-fold increase in the pulmonary vascular resistance index was seen in the muscle extract infusion group, which however returned to normal. Arterial hemoglobin concentration and systemic vascular resistance index remained fairly stationary in both groups. Immediate significant decreases in both arterial oxygen saturation and arterial oxygen tension were observed in the muscle extract group, however both variables recovered towards the end of the experiment. A slight increase in arterial blood pH value was noted during the experiment. In conclusion, autologous muscle extract infusion causes decreases in heart rate and cardiac index, as well as a significant increase in pulmonary vascular tone and systemic hypoxemia, emphasizing the detrimental effects of skeletal muscle injury following severe trauma.
Evaluation of Distal Anastomotic Intimal Hyperplasia: An Experimental Comparison by Arteriography, Duplex Sonography, Angioscopy, and Intravascular Ultrasound
Authors: Günen E. , Trubel W. , Schwarzacher S. , Herbst T. , Ullrich R. , Schima H. , Günen-Frank Andrea , Polterauer P.
Published: April 2003

Routine follow-up investigation methods after peripheral arterial bypass surgery, such as arteriography and colour duplex sonography, do not always allow correct analysis of moderate alterations in the vessel wall, e.g. initial stages of distal anastomotic intimal hyperplasia (DAIH). The aim of this study was to evaluate the efficiency of angioscopy and intravascular ultrasound compared to the named routine methods regarding detection of early DAIH. Eight months after bilateral femoropopliteal bypass surgery with venous grafts in 18 sheep, we investigated the distal anastomotic sites using the named methods. The findings were then correlated to histologic specimens. Intravascular ultrasound presented the highest sensitivity followed by angioscopy, with results markedly different from the findings arrived at by conventional methods.
Effect of Cautery with Irrigation Forceps on the Remnant Liver after Hepatectomy in Rats
Authors: Takao T. , Nishida M. , Maeda Y. , Hiraki S. , Takao K. , Tangoku A. , Oka M.
Published: April 2003

Monopolar cautery with irrigation forceps (CIF) was devised for use in liver resection that does not require occlusion of inflow to the remnant liver. However, a high power output is required to divide the hepatic parenchyma which boils the irrigation water. This study was performed to investigate the effects of using CIF on the hepatic parenchyma. Histologic and biochemical examination was performed in rats which had undergone hepatectomy using the CIF, irrigating bipolar (IB), Pringle’s maneuver with blunt dissection (group P), or a sham operation. A greater cautery distance was obtained with the CIF than the IB. There was no significant difference in the remnant liver function after the 1st postoperative day in any of the groups. CIF is an effective instrument for anatomic or nonanatomic hepatic resection.