Showing papers by "Gdańsk Medical University published in 2002"

Hepatocellular carcinoma in children: results of the first prospective study of the International Society of Pediatric Oncology group.

Abstract: PURPOSE: To improve survival and reduce operative morbidity and mortality in children with primary epithelial liver tumors by using preoperative chemotherapy, as well as to collect information on the epidemiology, natural history, and prognostic factors. PATIENTS AND METHODS: Forty children with hepatocellular carcinoma (HCC) were registered onto the Group for Epithelial Liver Tumors International Society of Pediatric Oncology’s first study from January 1990 to February 1994. The outcome could be analyzed in 39 of those patients. Disease was often advanced at the time of diagnosis; metastases were identified in 31% of the children and extrahepatic tumor extension, vascular invasion, or both in 39%. Multifocal tumors were common (56%). Thirty-three percent of tumors were associated with hepatic cirrhosis. All but two patients received preoperative chemotherapy (cisplatin and doxorubicin). RESULTS: Partial response was observed in 18 (49%) of 37 patients; there was no response or progression in the remainde...

Radiotherapy-related fatigue.

Abstract: Radiotherapy-induced fatigue is a common early and chronic side-effect of irradiation, reported in up to 80 and 30% of patients during radiation therapy and at follow-up visits, respectively. It is frequently underestimated by medical and nursing staff, only about 50% of patients discuss it with a physician and in one fourth of cases any intervention is proposed to the patient. The patients rarely expect fatigue to be a side-effect of treatment. The etiology of this common symptom, its correlates and prevalence are poorly understood. In numerous studies the level and time course of fatigue was demonstrated to depend on the site of tumor and treatment modalities. For example, psychological mechanisms have been proposed to explain fatigue in women receiving irradiation for early breast cancer, whereas decline in neuromuscular efficiency rather than psychological reasons can lead to the fatigue observed in patients undergoing radiotherapy for prostate cancer. Fatigue can affect global quality of life more than pain, sexual dysfunction and other cancer- or treatment-related symptoms. Several interventions have been tested in the management of radiotherapy-related fatigue and some randomized studies have been recently published. Although an optimal method has not yet been established, some promising results have been reported with relaxation therapy, group psychotherapy, physical exercise and sleep. Further methodologically correct studies are warranted to define better the causes, optimal prevention and management of this symptom.

Surgical view of the treatment of patients with hepatoblastoma: results from the first prospective trial of the International Society of Pediatric Oncology Liver Tumor Study Group.

Abstract: BACKGROUND Surgical resection is the cornerstone of treatment for patients with hepatoblastoma (HB). The Society of Pediatric Oncology Liver Tumor Study Group launched its first prospective trial (SIOPEL-1) with the intention to treat all patients with preoperative chemotherapy and delayed surgical resection. The objective of this article was to assess the assumed surgical advantages of primary chemotherapy. METHODS Between 1990 and 1994, 154 patients age < 16 years with HB were registered on SIOPEL-1. The pretreatment extent of disease was assessed, and, after undergoing biopsy, patients were treated with cisplatin 80 mg/m2 intravenously over 24 hours and doxorubicin 60 mg/m2 intravenously over 48 hours by continuous infusion (PLADO). Generally, tumors were resected after four of a total of six courses of PLADO. RESULTS One hundred twenty eight patients underwent surgical resection (13 patients underwent primary surgery, and 115 patients underwent delayed surgery after PLADO). A pretreatment surgical biopsy was performed in 96 of 128 patients (75%). Biopsy complications occurred in 7 of 96 patients (7%). Twenty-two patients showed pulmonary metastases at the time of diagnosis, and 7 patients underwent thoracotomy. Operative morbidity and mortality were 18% and 5%, respectively. Complete macroscopic surgical resection was achieved in 106 patients (92%), including 6 patients who underwent orthotopic liver transplantation. The actuarial 5-year event free survival (EFS) rate for all 154 patients in the study was 66%, and the overall survival (OS) rate was 75%. For the 115 patients who were included in the surgical analysis that followed the exact protocol, the EFS and OS rates were 75% and 85%, respectively. CONCLUSIONS Biopsy is a safe procedure and should be performed routinely. Preoperative chemotherapy seems to make tumor resection easier. Reresection of a positive resection margin does not necessarily have to be performed, because postoperative chemotherapy showed good results. Resection of lung metastases can be curative if there is local control of the primary tumor; however, results showed that the patient's prognosis was worse. Surgical morbidity or mortality rates were not necessarily higher in large multicenter studies. More importantly, countries of lesser economic status also can contribute effectively to these trials. Cancer 2002;94:1111–20. © 2002 American Cancer Society. DOI 10.1002/cncr.10282

Megamitochondria formation ‐ physiology and pathology

Abstract: Mitochondria undergo structural changes simultaneously with their functional changes in both physiological and pathological conditions. These structural changes of mitochondria are classified into two categories: simple swelling and the formation of megamitochondria (MG). Data have been accumulated to indicate that free radicals play a crucial role in the mechanism of the MG formation induced by various experimental conditions which are apparently various. These include ethanol-, chloramphenicol- and hydrazine-induced MG formation. Involvement of free radicals in the mechanism of MG formation is showed by the fact that MG formation is successfully suppressed by free radical scavengers such as alpha-tocopherol, coenzyme Q(10), and 4-OH-TEMPO. Detailed mechanisms and pathophysiological meanings of MG formation still remain to be investigated. However, a body of evidence strongly suggests that enormous changes in physicochemical and biochemical properties of the mitochondrial membranes during MG formation take place and these changes are favorable for membrane fusion. A recent report showed that continous exposure of cells with MG to free radicals induces apoptosis, finding which suggests that MG formation is an adaptative process to unfavorable environments at the level of intracellular organelles. Mitochondria try to decrease intracellular reactive oxygen species (ROS) levels by decreasing the consume of oxygen via MG formation. If mitochondria succeed to suppress intracellular ROS levels, MG return to normal both structurally and functionally, and they restore the ability to actively synthesize ATP. If cells are additionally exposed to excess amounts of free radicals, MG become swollen, membrane potential of mitochondria (DeltaPsim) decreases, cytochrome c is released from mitochondria, leading to activation of caspases and apoptosis is induced.

Relationship Between Muscle Sympathetic Nerve Activity and Diurnal Blood Pressure Profile

Abstract: The physiological mechanisms mediating the variability and diurnal rhythm of blood pressure are unclear. We tested the hypothesis that resting sympathetic activity is linked to the variability characteristics and 24-hour profile of ambulatory blood pressure measurements. We evaluated the relationship between muscle sympathetic nerve activity (MSNA) and the level, variability, and nocturnal fall of ambulatory blood pressure in 69 normal men. Subjects were subdivided according to the tertiles of MSNA distributions. Mean 24-hour blood pressure was not significantly different across the 3 groups. Compared with subjects in the first tertile (lowest MSNA, 25 bursts/min) had significantly greater daytime blood pressure variability, whether expressed as absolute values (10.2+/-0.5 versus 8.1+/-0.4 mm Hg for systolic blood pressure and 9.4+/-0.4 versus 7.2+/-0.4 mm Hg for diastolic blood pressure; P<0.01 for both comparisons) or as variation coefficients (8.1+/-0.4% versus 6.6+/-0.3% for systolic blood pressure and 12.7+/-0.7% versus 10.1+/-0.6% for diastolic blood pressure; P<0.01 for both comparisons). Subjects in the third tertile also had a more striking absolute and percentage fall in systolic blood pressure from daytime to nighttime than subjects in the first tertile (17+/-2 versus 10+/-2 mm Hg, P=0.02, or 13+/-1% versus 8.2+/-1.4%, P=0.02). In conclusion, higher resting measurements of sympathetic traffic are associated with greater daytime blood pressure variability and a more marked nocturnal decline in blood pressure in normal subjects. These findings suggest that sympathetic neural mechanisms may contribute importantly to the regulation of blood pressure over the 24-hour period.

Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell sarcoma of tendons and aponeuroses

Abstract: Clear cell sarcoma (CCS) is a rare malignant soft tissue tumor particularly associated with tendons and aponeuroses. The cytogenetic hallmark is the translocation t(12;22)(q13;q12) resulting in a chimeric EWS/ATF1 gene in which the 3'-terminal part of EWS at 22q is replaced by the 3'-terminal part of ATF1 at 12q. To date, only 13 cases of CCS have been analyzed for fusion genes at the transcription level, and there is no information about the breakpoints at the genomic level. In the present study, we describe the molecular genetic characteristics of CCS from 10 patients. Karyotypes were obtained from 10 cases, 7 of which showed the characteristic t(12;22). As an initial step in the characterization of the EWS/ATF1 and ATF1/EWS chimeras, we constructed an exon/intron map of the ATF1 gene. The entire ATF1 gene spanned >40 kb and was composed of 7 exons. Intron 3, in which most of the genomic breakpoints occurred, was to a large extent (83%) composed of repetitive elements. RT-PCR amplified EWS/ATF1 cDNA fragments in all patients and ATF1/EWS cDNA fragments in 6 of 10 patients. Four types of EWS/ATF1 chimeric transcript, designated types 1-4, were identified. The most frequent chimeric transcript (type 1) was an in-frame fusion of exon 8 of EWS with exon 4 of ATF1. This was the only chimeric transcript in 5 patients but found together with other variants in 3 tumors. The type 2 transcript of EWS/ATF1, an in-frame fusion of exon 7 of EWS with exon 5 of ATF1, was detected in 4 patients, as the only transcript in 1 case and together with other variants in 3 cases. An in-frame fusion of exon 10 of EWS with exon 5 of ATF1 (type 3) was found in 1 patient as the only transcript, and an out-of-frame fusion of EWS exon 7 with ATF1 exon 7 (type 4) was detected in 1 patient together with type 1 and type 2 transcripts. Sequencing of the amplified ATF1/EWS cDNA fragments showed in 5 patients that ATF1 exon 3 was fused with EWS exon 10, resulting in an out-of-frame chimeric transcript. In 1 case, nt 428 of ATF1 (exon 4) was fused with EWS exon 8; at the junction, there was an insertion of 4 nucleotides, also resulting in an out-of-frame transcript. Genomic extra long PCR and sequence analysis mapped the genomic breakpoints to introns 7, 8 and 9 of EWS and intron 3 and exon 4 of ATF1. While a simple end-to-end fusion was observed in 2 cases, additional nucleotides were found at the junctions in 2 other cases. In addition, topoisomerase I consensus sequences were found close to the junctions, suggesting that this enzyme may participate in the genesis of the EWS/ATF1 fusion.

Genotyping of bacteria belonging to the former Erwinia genus by PCR-RFLP analysis of a recA gene fragment.

Abstract: Genotypic characterization, based on the analysis of restriction fragment length polymorphism of the recA gene fragment PCR product (recA PCR-RFLP), was performed on members of the former Erwinia genus. PCR primers deduced from published recA gene sequences of Erwinia carotovora allowed the amplification of an approximately 730 bp DNA fragment from each of the 19 Erwinia species tested. Amplified recA fragments were compared using RFLP analysis with four endonucleases (AluI, HinfI, TasI and Tru1I), allowing the detection of characteristic patterns of RFLP products for most of the Erwinia species. Between one and three specific RFLP groups were identified among most of the species tested (Erwinia amylovora, Erwinia ananas, Erwinia cacticida, Erwinia cypripedii, Erwinia herbicola, Erwinia mallotivora, Erwinia milletiae, Erwinia nigrifluens, Erwinia persicina, Erwinia psidii, Erwinia quercina, Erwinia rhapontici, Erwinia rubrifaciens, Erwinia salicis, Erwinia stewartii, Erwinia tracheiphila, Erwinia uredovora, Erwinia carotovora subsp. atroseptica, Erwinia carotovora subsp. betavasculorum, Erwinia carotovora subsp. odorifera and Erwinia carotovora subsp. wasabiae). However, in two cases, Erwinia chrysanthemi and Erwinia carotovora subsp. carotovora, 15 and 18 specific RFLP groups were detected, respectively. The variability of genetic patterns within these bacteria could be explained in terms of their geographic origin and/or wide host-range. The results indicated that PCR-RFLP analysis of the recA gene fragment is a useful tool for identification of species and subspecies belonging to the former Erwinia genus, as well as for differentiation of strains within E. carotovora subsp. carotovora and E. chrysanthemi.

Effect of tributyltin on adenylate content and enzyme activities of teleost sperm: a biochemical approach to study the mechanisms of toxicant reduced spermatozoa motility

Abstract: The effects of tributyltin (TBT) on the energy metabolism and motility of fish spermatozoa were investigated in vitro in African catfish and common carp. A significant (P<0.05) decrease of the duration and the intensity of motility was observed in catfish spermatozoa exposed to 0.27 microg/l TBT for 24 h. Exposure of catfish spermatozoa to 2.7-27 microg/l TBT caused an instant decrease in ATP content. In the presence of 27 microg/l TBT approximately 55% of the initial ATP concentration in catfish semen was lost after 60 min incubation while AMP concentrations increased and the total adenine nucleotide (TAN) pool remained unchanged. The reduction in sperm ATP levels could not be attributed to cell death since viability decreased only slightly over the period of exposure. In carp by contrast, none of the adenylates concentrations studied (ATP, ADP and AMP) were affected by TBT exposure at any experimental condition. However, carp sperm motility was significantly reduced by exposure to 2.7 microg/l TBT. Among the enzymes investigated only lactate dehydrogenase (LDH) in catfish sperm was significantly (P<0.01) affected by 27 microg/l TBT treatment with a reduction in activity of approximately 75%. Compared with carp sperm before TBT exposure, that of catfish had lower adenylate contents and overall lower enzymatic activities; this explains its slower sperm velocity and shorter duration of movement as measured by computer assisted sperm analysis (CASA). The present in vitro study shows that catfish spermatozoa are more sensitive to TBT exposure (and probably to other toxicants) than those of carp.

Effects of oestrogen deprivation on interleukin-6 production by peripheral blood mononuclear cells of postmenopausal women.

Abstract: Various hormones can influence the expression of interleukin-6 (IL-6) and oestrogens are the most extensively studied. There is, however, controversy about the nature of the IL-6 secreted by human cells and its regulation by 17beta-oestradiol. The aim of this work was to clarify whether oestrogen deprivation after menopause may contribute to an enhanced IL-6 production by peripheral blood mononuclear cells (PBMC) in postmenopausal women. Twenty-two healthy postmenopausal women, age range 45-63 years, with clinical symptoms of oestrogen deficiency were enrolled in the study. The control group consisted of 16 healthy young women, age range 22-31 years, with regular menses and who were not taking oral contraceptives. Levels of IL-6 in the sera and PBMC culture supernatants were measured by the biological B9 cell-proliferation assay and expression of the IL-6 gene in non-stimulated PBMC was detected by RT-PCR. The effect of 17beta-oestradiol on spontaneous IL-6 production by the PBMC of postmenopausal women was also studied in vitro and in vivo. Seventeen out of the twenty-two postmenopausal women were given hormonal replacement therapy of 50 microg 17beta-oestradiol/day transdermally and the spontaneous production of IL-6 by the PBMC was analysed after 6 and 12 months of treatment. The postmenopausal women had significantly higher serum levels of IL-6 than the young controls. The spontaneous production of IL-6 by non-stimulated PBMC into the culture supernatants was also significantly higher in the postmenopausal women compared with the young. We also found that IL-6 gene expression was present in the non-stimulated PBMC isolated directly from the venous blood of the majority of the postmenopausal women. Women with IL-6 gene expression in the non-stimulated PBMC had significantly lower serum levels of 17beta-oestradiol compared with those where the IL-6 gene was not expressed in the PBMC. Our in vitro experiments showed that 17beta-oestradiol at concentrations of 10(-9) M and 10(-10) M decreased spontaneous IL-6 production by the PBMC of postmenopausal women. In vivo treatment with 17beta-oestradiol transdermally also significantly decreased spontaneous IL-6 production by the PBMC of postmenopausal women after 12 months of the therapy. Our results indicate that oestrogen deprivation after menopause may enhance IL-6 production by the PBMC of postmenopausal women. We suspect that the late complications of oestrogen deficiency, such as osteoporosis, coronary heart disease and Alzheimer's disease, may be mediated by an exaggerated production of IL-6 - a cytokine which seems to play a pivotal role in the pathogenesis of these age-related diseases.

Antifungal activity of the essential oils from some species of the genus Pinus.

Abstract: The chemical composition of the essential oils from the needles of Pinus ponderosa (north american pine), P. resinosa (red pine) and P. strobus (eastern white pine) has been determined by GC/MS (FID). The essential oils from P. resinosa and P. ponderosa in comparison to P. strobus have been characterized by the higher content of beta-pinene (42.4%, 45.7% and 7.9% respectively). On the other hand, a-pinene (17.7%) and germacrene D (12.2%) were dominant compounds of P strobus. Moreover the essential oil from P. resinosa was more rich in myrcene-15.9%. Estragole and delta-3-carene, each one in amount ca 8% were identified only in P. ponderosa. The content of essential oils in the needles slightly varied--0.65%--P. resinosa, 0.4%--P strobus, 0.3%--P. ponderosa. The antifungal activity has been investigated towards Fusarium culmorum, F solani and F. poae. The strongest activity was observed for the essential oil from P. ponderosa, which fully inhibited the growth of fungi at the following concentrations--F. culmorum, F. solani at 2% and F. poae at 5%.

Standard Versus Intensified Chemotherapy With Granulocyte Colony-Stimulating Factor Support in Small-Cell Lung Cancer: A Prospective European Organization for Research and Treatment of Cancer–Lung Cancer Group Phase III Trial—08923

Abstract: PURPOSE: To assess the impact on survival of increasing dose-intensity (DI) of cyclophosphamide, doxorubicin, and etoposide (CDE) in small-cell lung cancer (SCLC). PATIENTS AND METHODS: Previously untreated SCLC patients were randomized to standard CDE (cyclophosphamide 1,000 mg/m2 and doxorubicin 45 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1 to 3 every 3 weeks, for five cycles) or intensified CDE (cyclophosphamide 1,250 mg/m2 and doxorubicin 55 mg/m2 on day 1, and etoposide 125 mg/m2 on days 1 to 3 with granulocyte colony-stimulating factor [G-CSF] 5 μg/kg/d on days 4 to 13 every 2 weeks, for four cycles). Projected cumulative dose was almost identical on the two arms, whereas projected DI was nearly 90% higher on the intensified arm. Two hundred forty-four patients were enrolled. The first 163 patients were also randomized (2 × 2 factorial design) to prophylactic antibiotics or placebo to assess their impact on preventing febrile leukopenia (FL). This report focuses on chemotherapy DI results. RE...

Adult type vs. Childhood hepatocellular carcinoma--are they the same or different lesions? Biology, natural history, prognosis, and treatment.

Abstract: Background. Differences in the biology, natural history, and treatment results of hepatocellular carcinoma (HCC) in children and adults were sought based on the literature and experience resulting from SIOPEL 1 trial. Procedure. In the SIOPEL1 study, 40 children with HCC were registered from January 1990 to February 1994. Outcome was analyzed in 39. In most cases, disease was advanced at diagnosis: 31% had metastases and 39% had extrahepatic tumor extension and/or vascular invasion. More than 50% of patients had multifocal tumors; 39% of tumors were associated with hepatic cirrhosis. All, but two patients, received preoperative chemotherapy (PLADO-cisplatin and doxorubicin). Outcome, response to treatment, and prognostic factors were analyzed using the SAS statistical package. Results. Overall survival (OS) at 5 years is 28% and EFS is 17% at median follow-up of 75 months (49-90). Partial response to chemotherapy was observed in 18 of 37 cases evaluated (49%). Complete tumor resection was achieved in 14 of the 39 patients (36%). Twenty (51%) never became operable. Multifocality of the tumor, presence of metastases, and PRETEXT grouping adversely influenced OS. A large number of "de novo" HCC cases, fairly high response rate to preoperative chemotherapy (49%) and 54% survival after complete resection constitute a significant difference in comparison with adult HCC series. Conclusions. Survival for pediatric HCC patients is below 30%. Radical tumor resection remains the only chance for survival. New multi-center prospective studies in children with HCC are required to better results and to allow further study of differences between adult and pediatric HCC should they exist.

TGF-beta (transforming growth factor-beta) in chronic inflammatory conditions - a new diagnostic and prognostic marker?

Abstract: TGF-beta is a cytokine with varied properties and pleiotropic activity. It is released in an inactive form. To exhibit its biological activity, it requires binding to extracellular matrix proteins and, after that, proteolytic elimination of LAP (Latent Associated Protein) and LTBP (Latent TGF-beta Binding Protein). The process involves, among others, tissue transglutaminase, thrombin and plasmin. By stimulation of specific receptors, it influences transcription of some genes and translation of formed mRNA. Locally, it demonstrates proinflammatory properties whereas systemically, it has primarily a potent immunosuppressive effect. TGF-beta, by affecting proliferation, differentiation and migration of cells, as well as stimulation of extracellular matrix protein production, plays an important role in tissue regeneration and remodeling, but also in fibrosis. TGF-beta is also indispensable to maintain immune homeostasis of the organism. Reduced TGF-beta activity is considered to be responsible for development of autoimmune disorders in the course of several pathologic conditions. This cytokine plays an important role in the pathogenesis of chronic inflammatory processes taking place, among others, in inflammatory bowel diseases (IBD) and chronic hepatitis B and C. The paper presents a review of literature concerning diagnostic and prognostic value of TGF-beta level determinations in blood and tissue bioptates of patients with chronic non-specific enteritis and chronic hepatitis B and C.

Decortication in chronic pleural empyema — effect on lung function

Abstract: Objective: The aim of the present study is to evaluate the lung function before and after the lung decortication in patients with chronic pleural empyema (CPE). Methods: Twenty-six patients with diagnosis of CPE were evaluated in a prospective manner by lung perfusion scintigraphy, blood gas analysis and spirometry before and 35 weeks (^17) after the lung decortication. Results: Preoperative scintigraphy showed reduction of lung perfusion on the affected side to 24.5% (^12.6%) in 11 right side empyemas (predicted value 55%) and to 18% (^8%) in 15 left side empyemas (predicted value 45%). The postoperative measurements showed improvement in perfusion to 45.2% (^7.7%) in patients with right side empyema and 34.1% (^8.5%) with the left side affection. The preoperative vital capacity (VC) was reduced to 62.3% (^13.8%) of the predicted value and forced expiratory volume in 1 s (FEV1) to 50% (^15.5%) of the predicted value. Postoperatively, slight improvement was achieved to 79.8 % (^12.9%) for VC and 69.2% (^12.7%) for FEV1 . Blood gas analysis showed decreased values in majority of the patients before operation and significant improvement in postoperative evaluation. Conclusions: Perfusion and spirometry improves significantly in patients with CPE after the lung decortication but function of the affected lung remains impaired. There was no influence of the age, gender, side of the disease, bacteriology or duration of the empyema before operation on lung function. q 2002 Elsevier Science B.V. All rights reserved.

Frequency, consequences and pharmacological treatment of gastroesophageal reflux in children with cystic fibrosis.

Abstract: Background Gastroesophageal reflux (GER) may aggravate chronic bronchopulmonary diseases. The study evaluated GER frequency and characteristics in children with Cystic Fibrosis (CF) as well as its consequences and pharmacological treatment. Material/methods 40 CF children aged 1.3 to 20 years were examined. The study methodology involved: medical files analysis, anamnesis, physical examination, growth status estimation, esophageal pH-metry and upper gastrointestinal tract endoscopy with histological examination of esophageal biopsies. Results Based on pH-metry results, the diagnosis of GER was established in 22 children (55%). Mild GER (Index Reflux - IR 5-10%) was found in 12 children (54.5%), moderate GER (IR 10-20%) in 7 (31.8%) and severe GER (IR>20%) in 3 (13.6%). Ten patients with moderate or severe GER underwent endoscopy, which revealed GER-related esophagitis in 8 cases. There was no statistical difference of GER frequency and degree according to: age, sex, growth status, presence of type DF508 mutation in CFTR genome and typical GERD symptoms. According to the ESPGAN proposition, cisapride or cisapride with ranitidine medication was instituted. Treatment analysis was performed in 19 cases after successful follow-up examinations carried out three months later, indicating a significant decrease in reflux index, the longest episode duration and the number of episodes longer than 5 minutes. Improvement of endoscopic picture was noticed after treatment. Conclusions High frequency of gastroesophageal reflux and its consequences among children with cystic fibrosis, as well as the possibility of well-tolerated and efficient treatment of GER, indicate that diagnostics of GER among children with CF should be obligatory.

Comparison of the Ames test and a newly developed assay for detection of mutagenic pollution of marine environments.

Abstract: A new assay for detection of mutagenic pollution of marine environments, based on the use of a series of genetically modified Vibrio harveyi strains, was developed recently. Here, we compared this assay with a commonly used Ames test, employing mutants of Salmonella enterica serovar Typhimurium. We found that survival of S. enterica serovar Typhimurium in artificial marine water and in different samples of marine water is dramatically reduced relative to that of V. harveyi strains. This indicates that V. harveyi strains are significantly more useful in testing samples of marine water. Moreover, sensitivity of both assays was compared. We found that using the V. harveyi assay it is possible to detect significantly (from a few to several times) lower concentrations of typical chemical mutagens than employing the Ames test. Although the higher sensitivity of the V. harveyi test relative to the Ames assay may be of minor importance when testing mutagenicity of certain chemicals in their pure form under laboratory conditions, this feature is very important in testing samples of marine water. Therefore, we assume that the V. harveyi assay may be an adequate test for detection of mutagenic pollution of marine environments.

Relationship between acute and late normal tissue injury after postoperative radiotherapy in endometrial cancer.

Abstract: Purpose: To evaluate the relationship between acute and late normal tissue reactions in 317 consecutive endometrial cancer patients treated with surgery and adjuvant radiotherapy (RT). Methods: The data of 317 patients (staging according to the International Federation of Gynecology and Obstetrics) treated with postoperative RT were analyzed. Both low-dose-rate brachytherapy and external beam RT were applied in 247 patients (78%); brachytherapy only in 49 (15%) and external beam irradiation only in 21 (7%). The median follow-up was 7.3 years (range 4–21). The European Organization for Research and Treatment of Cancer Radiation Therapy Oncology Group system with elements of the late effects of normal tissue subjective objective management analytic (LENT/SOMA) scale was used to score the RT reactions. The correlation between the occurrence and severity of acute and late bowel and bladder toxicity as well as the relationship between the severity of acute effects and time to occurrence of late reactions were assessed using linear and logistic regression analyses. Results: Of the 317 patients 268 (85%) experienced acute RT reactions of any grade. Severe acute bowel reactions were observed in 15 patients (5%) urinary bladder complications in 1 patient (0.5%) cutaneous in 1 patient (0.5%) and vaginal in 1 patient (0.5%). Severe acute hematologic toxicity was seen in 3 patients (1%). A total of 158 patients (51%) experienced late RT reactions of any grade. Severe late bowel reactions were observed in 19 patients (6%) urinary bladder in 5 (2%) vaginal in 3 (1%) and bone in 10 (4%). When all toxic events were considered there was a highly significant correlation between the acute and late bowel reactions (p <0.001) but the acute and late urinary bladder reactions did not correlate (p = 0.64). The grade of acute toxicity was found to predict the grade of late toxicity for the bowel but not for the bladder (p <0.001 and p = 0.47 respectively). The severity of acute bowel and bladder toxicity did not correlate with the time to occurrence of late toxicity in these locations (p = 0.34 and p = 0.47 respectively). Conclusion: Patients with increased acute bowel toxicity during postoperative RT for endometrial cancer have an increased risk of late bowel injury. A higher grade of acute bowel complications correlated with more severe late events but was not predictive for its latency time. These findings suggest the possibility of an early indication of patients with an increased risk of late toxicity in whom preventive measures might be attempted. (authors)

Effect of Aluminum on Acetyl‐CoA and Acetylcholine Metabolism in Nerve Terminals

Abstract: The potential ability of Al to affect cholinergic transmission was studied on synaptosomal fractions of rat brain incubated with pyruvate in depolarizing medium containing 30 mM K+. Addition of 1 mM Ca caused a 266% increase in the acetylcholine (ACh) release despite decreased pyruvate oxidation. Under these conditions, 0.25 mM Al did not affect pyruvate oxidation but raised mitochondrial and decreased synaptoplasmic acetyl-CoA. Simultaneously, a 61% inhibition of Ca-evoked ACh release was observed. Verapamil (0.1 and 0.5 mM) decreased the acetyl-CoA concentration in synaptoplasm and inhibited ACh release. Al (0.012 mM) partially reversed these inhibitory effects. Omission of Pi from the medium abolished suppressive effects of Al on acetyl-CoA content and Ca-evoked transmitter release. We conclude that the Al(PO4)OH− complex may be the active form of Al, which, by interaction with the verapamil binding sites of Ca channels, is likely to restrict the Ca influx to the synaptoplasm. This may inhibit the provision of acetyl-CoA to the synaptoplasm as well as the Ca-evoked ACh release. One may suppose that excessive accumulation of Al in some encephalopathic brains may, by this mechanism, suppress still-surviving cholinergic neurons and exacerbate cognitive deficits caused by already-existing structural losses in the cholinergic system.

Renoprotective effect of small doses of losartan and enalapril in patients with primary glomerulonephritis. Short-term observation.

Abstract: Background: The renin-angiotensin system is thought to be involved in progression of chronic renal diseases of both diabetic and nondiabetic origin. It is confirmed that angiotensin