Reference natural radionuclide concentrations in Australian soils and derived terrestrial air kerma rate.

Sediment from drainage catchment outlets has been shown to be a useful means of sampling large land masses for soil composition. Naturally occurring radioactive material concentrations (uranium, thorium and potassium-40) in soil have been collated and converted to activity concentrations using data collected from the National Geochemistry Survey of Australia. Average terrestrial air kerma rate data are derived using the elemental concentration data, and is tabulated for Australia and states for use as baseline reference information.

Terrestrial gamma radiation baseline mapping using ultra low density sampling methods.

Baseline terrestrial gamma radiation maps are indispensable for providing basic reference information that may be used in assessing the impact of a radiation related incident, performing epidemiological studies, remediating land contaminated with radioactive materials, assessment of land use applications and resource prospectivity. For a large land mass, such as Queensland, Australia (over 1.7 million km(2)), it is prohibitively expensive and practically difficult to undertake detailed in-situ radiometric surveys of this scale. It is proposed that an existing, ultra-low density sampling program already undertaken for the purpose of a nationwide soil survey project be utilised to develop a baseline terrestrial gamma radiation map. Geoelement data derived from the National Geochemistry Survey of Australia (NGSA) was used to construct a baseline terrestrial gamma air kerma rate map, delineated by major drainage catchments, for Queensland. Three drainage catchments (sampled at the catchment outlet) spanning low, medium and high radioelement concentrations were selected for validation of the methodology using radiometric techniques including in-situ measurements and soil sampling for high resolution gamma spectrometry, and comparative non-radiometric analysis. A Queensland mean terrestrial air kerma rate, as calculated from the NGSA outlet sediment uranium, thorium and potassium concentrations, of 49 ± 69 nGy h(-1) (n = 311, 3σ 99% confidence level) is proposed as being suitable for use as a generic terrestrial air kerma rate background range. Validation results indicate that catchment outlet measurements are representative of the range of results obtained across the catchment and that the NGSA geoelement data is suitable for calculation and mapping of terrestrial air kerma rate.

A new Certified Reference Material for radionuclides in Irish sea sediment (IAEA-385).

A new Certified Reference Material (CRM) for radionuclides in sediment (IAEA-385) is described and the results of the certification process are presented. Eleven radionuclides ((40)K, (137)Cs, (226)Ra, (228)Ra, (230)Th, (232)Th, (234)U, (238)U, (238)Pu, (239+240)Pu and (241)Am) have been certified and information mass activities with 95% confidence intervals are given for seven other radionuclides ((90)Sr, (210)Pb((210)Po), (235)U, (239)Pu, (240)Pu and (241)Pu). Results for less frequently reported radionuclides ((60)Co, (99)Tc, (134)Cs, (155)Eu, (224)Ra and (239)Np) and information on some activity and mass ratios are also reported. The CRM can be used for quality assurance/quality control of the analysis of radionuclides in sediment samples, for the development and validation of analytical methods and for training purposes.

Efficacy of a toxicity-adjusted topotecan therapy in recurrent small cell lung cancer.

The present prospective multicentre trial investigated whether topotecan, given at a starting dose of 1.25 mg.m(-2) with individual dose adjustment, can improve safety in patients with relapsed/refractory small cell lung cancer without loss of efficacy. Patients received topotecan intravenously on days 1-5, every 21 days, for up to six courses. In the absence of relevant haematotoxicities, topotecan was increased to 1.5 mg.m(-2) and reduced to 1.0 mg.m(-2) in case of severe haematotoxicities. Of 170 recruited patients, 73.2% had stage IV disease and 63.4% had platinum-containing pre-treatment. Patients received a total of 521 courses. In 72.6% of those courses, the dose remained at 1.25 mg.m(-2); in 9.1% it was reduced and in 18.3% it increased. Overall response rate was 14.1% including one complete response; 28.8% had stable disease. Median duration of response was 13.6 weeks and median survival was 23.4 weeks. Clinical benefit was obvious for sensitive as well as for refractory patients. Haematotoxicity of grade 3 or 4 was clearly lower compared with the standard dose of 1.5 mg.m(-2). In conclusion, topotecan at a dose of 1.25 mg.m(-2) appears to be as effective as the dose of 1.5 mg.m(-2), but with reduced toxicity. Since patients with recurrent small cell lung cancer have a poor prognosis, they benefit especially from good tolerability.

Weekly docetaxel in patients with pretreated metastatic breast cancer: a phase II trial.

Docetaxel has consistently demonstrated its high activity as an antineoplastic agent in the treatment of metastatic breast cancer. However, 90% of patients receiving the recommended dose of 100 mg/m2 every 3 weeks will develop grade 3 or 4 neutropenia. Recent data suggest that the safety profile of a weekly docetaxel regimen compared favorably with the standard 3-week schedule. Thus, we initiated a phase II study to assess the efficacy and toxicity of weekly docetaxel in pretreated patients with metastatic breast cancer. Twenty patients with advanced, anthra-cycline-refractory breast cancer were included in this phase II trial. Docetaxel was administered at a starting dose of 40 mg/m2, repeated once a week for 3 consecutive weeks followed by a 1-week rest period (1 cycle). Patients were evaluated for tumor response every 8 weeks (after every other cycle). Therapy was continued for a maximum of six courses in patients showing tumor response or stable disease. Twenty patients received a total of 204 weekly infusions of docetaxel. The mean number of treatments was 10.2 (range 1-18). Eighteen patients were assessable for response. Five patients achieved a partial response and six patients showed either stable disease or a minor response. Seven patients had disease progression. The median survival was 7.8 months. Grade 3/4 leukopenia occurred in two patients. No other grade 3 or 4 hematologic toxicities were observed. The following grade 3/4 non-hematologic toxicities were seen: nausea/vomiting (one patient), infection (one patient), mucositis (two patients) and diarrhea (one patient). Three patients withdrew from the study due to dose-limiting toxicities (one due to severe neutropenia and two due to mucositis). We conclude that administration of docetaxel at a dose of 40 mg/m2 was effective and well tolerated even in heavily pretreated patients with metastatic breast cancer. This regimen is associated with only mild myelosuppression.

Acute transient encephalopathy after paclitaxel infusion: report of three cases.

Paclitaxel (Taxol) is a diterpene plant product and antineoplastic agent that promotes the assembly of microtubules as well as stabilizing their formation by preventing depolymerization. Myelosuppression was found to be dose-limiting, but peripheral neurotoxicity is also a well known side-effect. Central nervous system toxicity is rare, probably because paclitaxel does not cross the blood-brain barrier. We observed three patients who presented with acute encephalopathy within 6 h after infusion of paclitaxel at normal doses. All patients had received prior whole brain irradiation (WBI) and one patient had prior brain metastasectomy. Computer tomography and magnetic resonance imaging showed no evidence of cerebral metastases. An effect from other organ toxicities was excluded in all patients. All recovered spontaneously within 4-6 h. From this we can conclude that paclitaxel can cause severe acute transient encephalopathy, which may occur more frequently after prior WBI and/or surgery due to alteration of small vessel function.

Combined systemic and intraventricular chemotherapy in primary CNS lymphoma: a pilot study.

The objective was to evaluate response rate, response duration, and toxicity after systemic and intraventricular chemotherapy in primary CNS lymphoma (PCNSL). From September 1995 to September 1998, 20 consecutive patients with PCNSL (median age 64, range 27 to 71 years) were enrolled in a pilot study evaluating chemotherapy without radiotherapy. A high dose methotrexate (MTX) (cycles 1, 2, 4, 5) and cytarabine (ara-C) (cycles 3, 6) based systemic therapy (including dexamethasone, vinca alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ara-C. Complete response was achieved in 11 and partial remission in two patients; in one response could not be determined. Four patients showed progressive disease and two (70, 71 years) died from treatment related complications. Observation time was 2 to 59 months (median 31.5 months). Kaplan-Meier estimate for median time to treatment failure (TTF) was 20.5 months, and for median survival 54 months. Systemic toxicity was mainly hematological. Ommaya reservoir infection occurred in four patients and acute transient MTX induced encephalopathy in two (subacute in another). Cognitive dysfunction possibly due to treatment was seen in only one patient after relapse and after a total of 12 cycles (six at relapse). In conclusion, primary chemotherapy based on high dose MTX and ara-C is highly efficient in PCNSL. Toxicity is manageable in patients younger than 70 years.

Augmentation of 17-1A-induced antibody-dependent cellular cytotoxicity by the triple cytokine combination of interferon-alpha, interleukin-2, and interleukin-12.

Previously, interferon-alpha (IFN-alpha), interleukin-2 (IL-2), and interleukin-12 (IL-12) were shown to increase the antibody-dependent cellular cytotoxicity (ADCC) induced by the murine monoclonal antibody 17-1A, which recognizes the tumor-associated antigen EpCAM. In this study, the authors wanted to determine whether the combination of these three cytokines would yield greater cytotoxicity than the single cytokines. For cytotoxicity assessment, a new flow cytometric assay was used that allows the analysis of long-term ADCC exerted by macrophages. Peripheral blood mononuclear cells from healthy donors were used as effector cells against the colorectal carcinoma cell line HT29 at a low effector-to-target ratio of 4.5:1. With this test, the effectiveness of the combinations IL-2 and IFN-alpha, IL-2 and IL-12, and IL-12 and IFN-alpha were compared with each other. The combinations IL-2 plus IL-12 and IFN-alpha plus IL-12 were more potent at the concentrations tested. Furthermore, the triple cytokine combination of IFN-alpha, IL-2, and IL-12 revealed significantly greater ADCC than dual cytokine combinations. Next, CD14+, CD4+, and CD4- cells were isolated by paramagnetic beads and magnetic activated cell sorter (MACS) columns. The CD14+ and CD4- cell populations contained the ADCC effectors. The addition of CD4+ cells to CD14+ or CD4- cells resulted in augmented ADCC, indicating that cooperation between immune cells occurs. These results suggest that multiple cytokine combinations with monoclonal antibodies may be more effective for cancer immunotherapy.

[Therapy-refractory thrombocytopenia in chronic hepatitis C]. / Therapierefraktäre Thrombozytopenie bei chronischer Hepatitis C.

HISTORY AND CLINICAL FINDINGS: A 74-year-old man known to be suffering from a chronic hepatitis C infection was hospitalized because of intestinal hemorrhage, multiple petechiae and suggillations. The patient had received oral anticoagulant medication after replacement of the mitral valve. The intake of oral vitamin K antagonist had been discontinued eight days before admission. EXAMINATION FINDINGS: On admission, the platelet count was 3 G/l, the Quick's test 72%. Colonoscopy revealed diffuse mucosal bleeding in the proximal colon. Bone marrow examination showed moderate hyperplasia of erythropoiesis, as well as a marked increase in megakaryocytes. DIAGNOSIS, THERAPY AND COURSE: The diagnosis was hepatitis C-associated idiopathic thrombocytopenic purpura. The administration of both immunoglobulins and prednisone failed to increase platelets sufficiently. There was also no improvement after administration of Danazol. However, six days after a single application of cyclophosphamide (2,000 mg on day 1), a continuous increase of platelets to 100 G/l was obtained, a level which has remained stable for the last 18 months. CONCLUSION: The differential diagnosis of a hepatitis C-associated autoimmune thrombocytopenia must be considered in patients with chronic hepatitis C infection and severe thrombocytopenia. In cases of refractory disease, treatment with cyclophosphamide may be successful. This is particularly appropriate if, in the case of an insufficient increase in thrombocytes following administration of immunoglobulins, the success of a splenectomy is improbable, or when a splenectomy must be excluded because of relative or absolute contraindications.

Primary central nervous system lymphoma: a clinicopathological study of 28 cases.

A group of 28 consecutive patients (mean age 59 years) with primary central nervous system lymphoma (PCNSL) was treated with different regimens, including steroids only, radiotherapy (RT), chemotherapy or combinations of all. Lymphoma was classified as high grade malignant B-cell non-Hodgkin's lymphoma of the diffuse large cell type in each of these cases. RT alone led to tumour remission in more than 70 per cent, survival could be prolonged with additional chemotherapy. Thirteen patients were treated with chemotherapy alone; nine of them received a novel combined intraventricular and systemic polychemotherapy protocol based on high dose methotrexate (MTX) and high dose cytarabine (ara-C). The response rate was 90 per cent with 80 per cent complete responses. Neurotoxicity, i.e. white matter lesions associated with severe cognitive dysfunction affected both patients surviving RT more than a year and patients treated with combination RT/chemotherapy. Confluent white matter hyperintense lesions were detectable on MRI in three out of 13 patients treated with chemotherapy alone, however, cognitive dysfunction has not been detected in these patients.

Enhancement of antibody dependent cellular cytotoxicity (ADCC) by combination of cytokines.

Monoclonal antibodies (MAb) specific for tumor-associated antigens (TAA) can induce an immunological cellular attack of tumor cells by a process termed antibody dependent cellular cytotoxicity (ADCC). Cytokines may augment ADCC by direct activation of immune cells or by enhancement of TAA on tumor cells. Thus, we investigated whether ADCC by MAb 17-1A and BR55-2, which recognize TAA on colorectal tumor cells, can be augmented by 3-day incubation with different concentrations of IL-2, IL-4, IL-6, IL-12, IFN-alpha, IFN-gamma, GM-CSF, M-CSF, and TNF-alpha. ADCC was assessed by a new flowcytometric cytotoxicity assay (Flieger et al. Immunol Methods 1995; 180:1-13) using PKH-2 labeled HT29 cells as targets and PKH-26 labeled peripheral blood mononuclear cells from three healthy volunteers as effector cells. We found three reaction patterns with the cytokines tested: (a) cytokines, which increase ADCC (IL-2, IL-12, IFN-alpha, and IFN-gamma, which represent Thl cytokines); (b) cytokines with no effect (GM-CSF, M-CSF, and TNF-alpha); and (c) cytokines, which decrease ADCC (IL-4 and IL-6, which represent Th2 cytokines). Then, we tested cytokines that increase ADCC in combination with the other cytokines. We found that the combinations IL-2/IFN-alpha, IL-2/IFN-gamma, IL-2/IL-12, and IL-12/IFN-alpha potentiated ADCC. By contrast, IL-4 reduced the IL-2, IL-12, and IFN-alpha-induced ADCC. Since the Thl response, cooperation of monocytes and CD4 cells is involved, we plan to elucidate by magnetic cell sorting (MACS) separation techniques, which cells are involved in cytokine-induced ADCC. Our results may be useful for finding combinations of cytokines and MAb for the locoregional treatment of colorectal cancer.

I-131-Lipiodol therapy in liver neoplasms.

Twelve patients with liver neoplasms [10 HCC, 1 CCC, 1 multiple breast cancer metastases (BCM)] were treated by transarterial I-131-Lipiodol. Computed tomography (CT) and single photon emission CT (SPECT) showed pronounced I-131-Lipiodol accumulation in the tumor tissue in all cases. In three patients with HCC a reduction of tumor size was achieved after the first treatment. The remaining patients had big tumor masses; 5 of these (4 HCC, 1 CCC) had stable disease after the first treatment, and 2 HCC were progressive. One patient died immediately after therapy due to other reasons. The BCM proved significant reduction in number and size. Eighteen-FDG-PET (positron emission tomography with fluor-18-deoxy-glucose) and CT controls showed in part different results with pretherapeutic PET proving high interindividual variability in tumor activity. Side effects were tolerable. In summary, the therapy procedure with transarterial I-131-Lipiodol is safe and effective in tumors with moderate tumor mass.

Geotrichum capitatum septicaemia in neutropenic patients: case report and review of the literature.

We report a case of systemic infection with Geotrichum capitatum in a patient with acute myeloid leukaemia. Three days before death, the patient developed acute renal failure, probably caused by occlusion of glomerula with hyphae of G. capitatum. Up until now, prophylaxis and treatment of infections caused by Geotrichum capitatum have not been established. However, the prophylactic administration of high-dose itraconazole and the therapeutic use of liposomal amphotericin B are subjects of discussion.

Effect of season and soil treatments on carbohydrate concentrations in Norway spruce (Picea abies) mycorrhizae.

We studied effects of season and soil treatments (watering, acidification, liming and combinations of these treatments) on soluble carbohydrates of mycorrhizal roots of Norway spruce (Picea abies (L.) Karst.). Arabinose, arabitol, fructose, glucose, inositol, lactose, mannitol, pinite, quinate, raffinose, shikimate, stachyose and trehalose were identified by HPLC. Concentrations of inositol, lactose and pinite were constant throughout the year, whereas concentrations of raffinose, stachyose and trehalose were higher in winter than in summer, and concentrations of glucose, fructose and mannitol increased from February to September. Soil acidification and liming had no effect on the annual mean concentrations of fructose, glucose, lactose, pinite, raffinose and stachyose. Liming increased quinate concentrations and decreased arabitol concentrations. Annual mean concentrations of arabinose and mannitol decreased in response to soil acidification. Annual mean concentrations of inositol increased in response to irrigation. None of the soil treatments affected the mean annual concentration of trehalose.

Oral idarubicin, dexamethasone and vincristine (VID) in the treatment of multiple myeloma.

In order to replace the central venous line necessary for continuous infusion of vincristine and doxorubicin with high-dose dexamethasone (VAD) and to avoid hospitalization, we evaluated the efficacy and toxicity of oral idarubicin, vincristine and dexamethasone (VID) in patients with multiple myeloma. Vincristine (1.6 mg/m2, max 2 mg) was given as a bolus injection on day 1. Idarubicin was given in capsules 10 mg/m2/day for days 1-4 with an intraindividual dose escalation, 40 mg dexamethasone were given on days 1-4, 9-12, 17-20. Treatment cycles were repeated every 28 days. At this interim analysis, 53 patients have been entered into the ongoing trial; 46 patients are evaluable for toxicity. The median age was 60 years (interquartile range, 52-65). 46% were primary or secondary refractory, 20% had previously been treated with VAD and 30% had previously untreated disease, 4% had two or more relapses. Four patients died within 2 months from entry and were considered as early deaths (8.7%). 45% of the 42 patients evaluable for efficacy achieved a partial remission and 26% a minor remission. The median reduction of the M-component was 43% (interquartile range, 25-64%). VID is an effective and convenient alternative to VAD even in relapsed or refractory patients.

[Change in the etiology and sequelae of severe eye injuries. A comparison of 197 personal patient admissions with other reports from the literature]. / Veränderte Ursachen und Folgen schwerer Augenverletzungen. Ein Vergleich von 197 eigenen stationär behandelten Patienten mit anderen Literaturberichten.

The spectrum of severe eye-injuries has clearly changed. We have analysed the documents of 197 patients treated in our clinic from 1988-1990. Of 119 (60.4%) contusions and 78 (39.6%) perforating injuries only 25.3% were occupational accidents. A more detailed analysis showed above all an increase of sport- and leisure-injuries and a considerable decrease of traffic-injuries (4.6%). Shocking is in contrast the percentage (10.7%) of severe injuries by brutality. More details concerning the consequences of injuries are presented and compared with older statistics. From this conclusions are drawn for better prophylaxis.

[The effectiveness of intratracheal antibiotic administration. Clinical, microbiologic and pharmacologic results]. / Die Wirksamkeit intratrachealer Antibiotikaapplikation. Klinische, mikrobiologische und pharmakologische Ergebnisse.

In 199 artificially ventilated patients of an internal intensive care unit clinical, bacteriological and pharmacological effects of endotracheally administered gentamicin were investigated. The dose schedule was 2-4 x 40 mg gentamicin/day. The incidence of secondary achieved pneumonia was reduced from 70% to 18%. The endotracheal colonization of pathogenic microorganisms reached 29.6% concerning bacterial microorganisms and 61% concerning fungi, 51.8% of all specimen were sterile. During 4 years of investigation there were found 19 secondary resistances of different bacteria, 12 persisted. Serum concentrations of gentamicin under endotracheal administration of 40 mg in 6-h-intervals didn't reach therapeutic values. In case of renal disorder the dose interval should be prolonged to twelve hours.