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Ionizing radiation is the most thoroughly investigated exogenous noxa. Since the early 20th century it is well known that using ionizing radiation in diagnostic procedures causes cancer - physicians themselves frequently being struck by this disease in those early days of radiology. Radiation protection therefore plays an important role. Below doses of 100 Millisievert (mSv) however much research has to be accomplished yet because not only malignant tumors, but cardiovascular diseases, malformations and genetic sequelae attributable to low dose radiation have been described. Unborns, children and adolescents are highly vulnerable. Dose response correlations are subject to continuing discussions because data stem mostly from calculations studying Japanese atomic bomb survivors. Radiation exposure is not exactly known, and it is unknown, if observations of radiation induced diseases in this ethnicity can be generalized. Nowadays the main source of low dose ionizing radiation from medical diagnostics is due to computertomography (CT). Large recent clinical studies from the UK and Australia investigating cancer incidence after exposition to CT in childhood and adolescence confirm that low doses in the range of 5 mSv already significantly increase the risk of malignant diseases during follow up. Imaging techniques as ultrasound and magnetic resonance tomography therefore should be preferred whenever appropriate.

PEG-modified proteins have numerous advantages over their unmodified counterparts (increased half life, reduced antigenicity, improved solubility), but almost without exception, they show a modest to marked reduction in biological or enzymatic activity. However, while investigating a new protocol for the preparation of PEG-proteins, we compared PEG-modified and unmodified GM-CSF with respect to their polymorphonuclear neutrophil granulocyte (PMN) priming activities. PEG-GM-CSF was unexpectedly more active than GM-CSF in its ability to prime neutrophils to respond to the synthetic peptide n-formyl-methionyl-leucyl-phenylalanine (FMLP) with an oxidative burst (assessed both by nitroblue tetrazolium reduction and ferricytochrome c reduction). These results were in contrast to the findings for colony stimulating activity and with GM-CSF induced thymidine uptake, where the biological activity was unchanged or reduced. The enhanced neutrophil priming activity of PEG-GM-CSF was confirmed using FPLC fractionated PEG-modified GM-CSF. This showed changes in the bioactivity profile consistent with both the shift in protein elution profile and enhanced activity of the PEG-modified material (reflected in the increased area under the bioactivity curve). We also excluded a neutrophil priming action for PEG-modified fetal calf serum proteins, carrier proteins and 'irrelevant' cytokine, erythropoietin. The dissociation of the two bioactivities was confirmed using individual FPLC fractions. These results suggest the presence of differences in either binding, receptor/ligand processing or signal transduction for neutrophils versus progenitors, that are differentially affected by PEG-modification of GM-CSF. The demonstration that PEG-modification can partially dissociate two biological activities suggests the feasibility of using PEG-modification to produce proteins with subtly altered spectra of biological activity and hence new ranges of clinical applications.

This study reports on biological response modification induced by prolonged continuous subcutaneous (s.c.) infusion of recombinant interferon-gamma (rIFN-gamma) with particular attention to changes of soluble CD14. This glycoprotein with an unknown function is derived from myeloid cells carrying membrane CD14, which is the receptor for lipopolysaccharide (LPS)-LPS-binding protein (LBP) complexes. Fifteen metastatic cancer patients received weekly escalating doses of rIFN-gamma starting at either 50 or 100 micrograms/24 h and increasing up to 400 micrograms/24 h for a median duration of 6 weeks. The maximum tolerated dose was higher (200 micrograms/24 h) with the lower (50 micrograms/24 h) starting dose. Biological activity of rIFN-gamma was evaluated by weekly measurements of CD14, neopterin, and beta 2-microglobulin concentrations in serum as well as monocyte HLA class I and II antigen expression and tumor cytotoxicity. Serum IFN-gamma concentrations increased 20-fold within 4 weeks of therapy. The levels were correlated to the mean dose (r = 0.95, p less than 0.05). Among the biological markers, two patterns were observed. First, serum CD14 concentration and expression of monocyte HLA class II antigens increased significantly during the first week, and marker expression correlated with serum IFN-gamma levels (p less than 0.05); CD14 and HLA class II antigens thereafter returned to pretreatment levels within 4 weeks of therapy despite persistently elevated serum IFN-gamma concentrations. Second, serum neopterin and beta 2-microglobulin concentrations as well as monocyte HLA class I expression also increased significantly within the first week, but remained elevated thereafter without any further dose relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

A 48 year old Caucasian man with cutaneous T-cell lymphoma, stage IVB is described. Initially he presented with an ichthyosis-like dermatosis and developed lymphadenopathy, hypercalcaemia, hepatosplenomegaly and lymphomatoid papulosis over a period of 7 years. Following splenectomy he developed a leukemic phase which was refractory to polychemotherapy. Therapy with cyclosporin A initially caused deterioration of the skin infiltrations and the peripheral blood T-helper lymphocytosis. However after 3 weeks an improvement of the patient's general condition was noted including decreased skin involvement, reduction of hepatomegaly and a sustained decrease of the absolute lymphocytosis, which lasted for ten months. Lymphomatoid papulosis was not significantly affected by cyclosporin A. In conclusion, this case and several case reports from the literature suggest that cyclosporin A may be valuable in the palliative treatment of selected patients with advanced cutaneous T-cell lymphoma.

Local recurrences of intraperitoneal malignancies are mainly localized at the primary tumor site and the peritoneal surface. Surgical procedures alone are neither able to further reduce the development of local recurrence nor to treat the already established recurrent disease. In this situation intraperitoneal chemotherapy as an "adjuvant" treatment modality could be thought helpful. Experimental and clinical trials have shown that high doses of cytotoxic agents can be applied to the abdominal cavity with less systemic side effects. While the recent published data are not promising for gastrointestinal malignancies, they seem to be more encouraging for ovarian cancer.

Morphology, frequency and significance of capillary sclerosis (CS) in the ureter and electron microscopic findings in early papillary necrosis are described. CS of the urinary tract is characterized by a thickening of the basement membrane of capillaries lying just underneath the urothelium. The basement membrane changes can be demonstrated by PAS, Sudan stain and autofluorescence with equal reliability. By electron microscopy the thickened basement membranes exhibit a tree ring like pattern permeated by lipid vacuoles. CS is most often present in the renal pelvis and the ureter and only in particularly severe cases also in the urinary bladder. The most severe CS is found in the proximal and middle third of the ureter. In a prospective autopsy study CS was found in 3.5% of autopsies of adults and in 83% of clinically recognized phenacetin abusers. Since there is no association with other renal or metabolic diseases, CS can be considered as specific for phenacetin abuse. This finding is further substantiated by a significant correlation between the degree of severity of capillary sclerosis and the daily dose of phenacetin in grams. In about half of the patients with known analgesic abuse but without CS, possible causes for the lack of CS can be identified, of which the most important is regression of CS after stopping the abuse. Electron microscopic studies of early papillary necrosis show the same BM changes as in the ureter in peritubular capillaries, loops of Henle and similar BM alterations in the collecting ducts. The morphologic findings in the ureter and in the renal papilla suggest that CS in papillary necrosis are the consequence of a toxic damage of endothelial and in the kidney of endothelial and epithelial cells.

The costs chemotherapy for eight patients with different diagnoses treated between 1983 and 1985 were analyzed, based on case histories and invoices submitted to medical insurance companies. Total monthly costs of therapy included drug costs, diagnostic costs, fees and hospital charges. The total monthly chemotherapy costs ranged between SFr. 379.- and SFr. 6065.- and between SFr. 874.- and SFr. 3476.- for 5 outpatients and two inpatients respectively. Total monthly drug costs ranged between SFr. 103.- (Fluorouracil) and SFr. 1744.- (Adriamycin) for palliative therapies, and between SFr. 620.- (MOPP-ABVD) and SFr. 2490.- (Cis-Platin, Velbe, Bleomycin) for curative therapies. The drug costs (Methotrexate) of a third inpatient exceeded the flat rate paid by insurance, the remaining costs being covered by the state. About 50% of cancer chemotherapy costs are due to drug costs. Drug costs of curative therapies seem to be higher than those of palliative therapies. A reduction of total costs by more than 30% is possible if hospitalisation is avoided, which might be inacceptable for some patients. Our method gives an incomplete picture of total chemotherapy-related costs because it does not consider loss of earnings and costs borne by the state to cover the deficit. Possibilities to reduce chemotherapy costs in tumor patients are discussed.

In a group of 31 patients a port-a-cath-system for intraperitoneal chemotherapy was installed. From 23 evaluable patients 9 showed a tumor remission, but only 1 was a patient with gastrointestinal carcinoma. All others were patients with ovarial carcinoma. The median survival rate of all patients was 9 months after implantation of the intraperitoneal catheter. 50% of all patients with gastrointestinal carcinoma died within the first 6 months, only 1 of 11 patients with ovarial carcinoma died in this period.

In 442 inhabitants of Basel 451 malignant tumors of the lower urinary tract were found at autopsy or biopsy from 1963 to 1977. 69/442 patients were abusers of phenacetin containing analgesics. Carcinomas and sarcomas of the lower urinary tract were nearly 13 times as frequent in abusers as in non-abusers. Carcinomas of the renal pelvis were 77 times, carcinomas of the ureter 89 times and those of the urinary bladder 7 times as frequent among abusers. The differences in incidence of malignant tumors are statistically highly significant for all localizations and for multiple carcinomas as well, even if smokers are excluded. "Phenacetin tumors" occurred in younger patients and were more common in women than in non-abusers. They were ofen, though not always, accompanied by analgesic nephropathy. Comparison with other etiological factors such as aromatic amines or thorotrast demonstrated that phenacetin abuse is of greatest importance. The significance of smoking cannot be established unequivocally. Because of the occurrence of a large number of malignant tumors in phenacetin abusers it is very important to prohibit by legislation the use of phenacetin or paracetamol containing analgesics without medical prescription. In addition, these drugs should be replaced by other analgesic compounds.