Palliative treatments of cancers of upper respiratory and digestive tracts

Palliative treatment of head and neck cancers needs an initial evaluation based upon clinical symptoms and tumoral behaviour. Local recurrences are the most frequent presentation of tumoral failures. The therapeutic management of these local recurrences requires a mixture of unspecific and specific oncologic procedures. Radiotherapy and chemotherapy are frequently used in those circumstances in order to reduce the tumoral volume and to facilitate the effectiveness of unspecific treatments. Management of metastatic disease is often impaired by the moderate efficiency of chemotherapy while this treatment leads to marked side effects. Basically, the best therapeutic choice depends on the expected positive balance between the improvement of symptoms and the level of treatment-related side effects. However, daily clinical approach is a better way to care these patients than predefined rigid protocols.     

The inhibition of DMBA-induced carcinogenesis by neoxanthin in hamster buccal pouch

Neoxanthin, a major carotenoid pigment of spinach, is found in the Chloroplast membrane and has an unknown function in plants. Neoxanthin inhibited the production of superoxide anions in an artificial xanthine and xanthine oxidase system and depressed DNA synthesis in methylcholanthrene (MCA)-initiated C3H10T1/2 fibroblasts. in two-stage carcinogenesis experiments, neoxanthin at 0.2 micrograms/0.2 ml inhibited the formation of tumors that were induced sequentially by 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) in the buccal pouch of Syrian Golden hamsters. To assess the ongoing process of carcinogenesis, the activity of ornithine decarboxylase (ODC), required for cell proliferation, was analyzed. Neoxanthin inhibited the activity of ODC when animals were treated with neoxanthin one hour before the application of TPA in two-stage carcinogenesis. However, neoxanthin did not inhibit ODC activity when animals were treated with neoxanthin one hour before the application of DMBA in two-stage carcinogenesis, and there was no subsequent tumor formation. In a short-term anti-initiation experiment, neoxanthin inhibited the covalent binding of isotope-labeled DMBA to DNA by 53%. These results indicate that neoxanthin inhibits the initiation stage and the promotion stage in two-stage carcinogenesis. This suggests that neoxanthin may act as a potential chemopreventive agent.     

Endothelin-1 concentrations and optimisation of arterial oxygenation and venous admixture by selective pulmonary artery infusion of prostaglandin E1 during thoracotomy

PURPOSE: To demonstrate a superselective intraarterial chemotherapy as a therapeutic alternative in the treatment of previously treated recurrent lymph node metastases in breast cancer. METHODS: 14 patients with recurrent lymph node metastases in cases of breast cancer were presented to be treated by intraarterial chemotherapy of 25 mg mitoxantrone/m2 over a period of 24 hours. In two patients with superclavicular lymph node involvement an intraarterial therapy could not be carried out because of a vascular connection to the anterior spinal artery. Involved lymph stations could be reached in superselective technique by side branches of the subclavian artery. Heparin coverage was given intravenously. Every patient had had surgery, radiation, systemic chemo- and hormonal therapy before and was now graded as inoperable. Therapy indication was given by local tumour-induced symptoms. RESULTS: In the 12 treated cases complete remission was seen in three, partial remission in 4, a steady state in two and a progressive disease in three. There were no complications or severe side effects. CONCLUSION: Intraarterial chemotherapy is an effective and well tolerated treatment in recurrent lymph node metastases in cases of breast cancer even if conventional therapies can no longer be used.     

Perception of nuclear energy and coal in France and The Netherlands

This study focuses on the perception of large scale application of nuclear energy and coal in the Netherlands and France. The application of these energy-sources and the risks and benefits are judged differently by various group in society. In Europe, France has the highest density of nuclear power plants and the Netherlands has one of the lowest. In both countries scientists and social scientists completed a questionnaire assessing the perception of the large scale application of both energy sources. Furthermore, a number of variables relating to the socio cultural and political circumstances were measured. The results indicate that the French had a higher risk perception and a more negative attitude toward nuclear power than the Dutch. But they also assess the benefits of the use of nuclear power to be higher. Explanations for these differences are discussed.     

High-dose chemotherapy with carboplatin, etoposide and cyclophosphamide followed by a haematopoietic stem cell rescue in patients with high-risk retinoblastoma: a SFOP and SFGM study

This study investigates the role of high-dose chemotherapy with haematopoietic stem cell rescue as consolidation treatment in high-risk retinoblastoma (extraocular disease at diagnosis or relapse or invasion of cut end of optic nerve). 25 patients received high-dose chemotherapy including carboplatin (250 mg/m2/day from day 1 to day 5 for the 6 first patients and 350 mg/m2/day from day 1 to day 5 for the other patients), etoposide (350 mg/m2/day from day 1 to day 5) and cyclophosphamide (1.6 g/m2/day from day 2 to day 5) (CARBOPEC) followed by autologous haematopoietic stem cell rescue. 19 patients received this drug combination for chemosensitive extraocular relapse. The other 6 patients with histological high-risk factors were given this treatment as consolidation after enucleation and conventional chemotherapy. The three year disease-free survival was 67.1%. In 7 of the 9 relapsing patients, the first site of relapse was the central nervous system. All patients with central nervous system disease died except one. The main toxicity was haematological and digestive (mucositis and diarrhoea). 2 of the 13 evaluable patients had grade III and IV ototoxicity. One patient experienced an acute grade I reversible cardiotoxicity. The CARBOPEC regimen seems to be a promising therapeutic strategy in patients with high-risk retinoblastoma, especially those with bone and/or bone marrow involvement. This treatment did not improve the outcome of patients with central nervous system disease.     

The differential regulation and secretion of proteinases from fetal and neonatal fibroblasts by growth factors

Until recently, research on the pathogenesis of glomerulonephritis has been mainly focused on the characterization of humoral immune responses in the initiation of glomerular injury. However, there is a growing recognition that both cellular and humoral immune responses, in varying proportions, are involved in the pathogenesis of immunologically-mediated glomerulonephritis. T lymphocytes are essential cellular elements of cell-mediated immunity. Both in experimental models of immune-mediated renal disease and in histopathological analyses of human nephropathies, the involvement of T cells has been demonstrated in the immunoregulation of nephritogenic immune responses and in the immune injury in the kidney. T cell activation resulting in either delayed-type hypersensitivity, cytolytic reactions, abnormal expression of major histocompatibility complex (MHC) molecules, or B cell activation can result in glomerulonephritis. These different types of responses are exerted by distinct T cell subsets defined by cell surface markers and cytokine profiles. CD4+ T cells in vivo are functionally heterogeneous with respect to cytokine production and the CD45 isoforms that are found on their surface. Like CD4+ T cells, CD8+ T cells may also be heterogeneous at the level of cytokine production. The roles of CD4+ and CD8+ cells and their cytokine profiles in glomerulonephritis have not been extensively investigated yet, but such studies might improve the understanding of the pathogenesis and possibly lead to new therapeutic approaches of human glomerulonephritis. In this review the role of distinct T lymphocyte subsets in experimental and human glomerulonephritis will be discussed.     

A mixed-signal RAM decision-feedback equalizer for disk drives

A mixed-signal RAM decision-feedback equalizer (DFE) that operates at 90 Mb/s is described. In the analog domain, the DFE subtracts intersymbol interference caused by the past four outputs. The equalized signal is fed into a nonuniform flash analog-to-digital converter (ADC) to produce the decision output and error signal used to adapt the RAM contents in the digital domain. With a 5 V supply voltage, the power dissipation is 260 mW during steady-state operation. The active area is 4.5 mm² in a 1 μm CMOS process     

Distribution and connections of inspiratory premotor neurons in the brainstem of the pigeon (Columba livia)

We have recorded extracellular, inspiratory-related (IR) unit activity in the medulla at locations corresponding to those of neurons retrogradely labeled by injections of retrograde tracers in the lower brachial and upper thoracic spinal cord, injections that covered cell bodies and dendrites of motoneurons innervating inspiratory muscles. Bulbospinal neurons were distributed throughout the dorsomedial and ventrolateral medulla, from the spinomedullary junction through about 0.8 mm rostral to the obex. Almost all of the 104 IR units recorded were located in corresponding parts of the ventrolateral medulla, rostral to nucleus retroambigualis, where expiratory related units are found. Injections of biotinylated dextran amine at the recording sites labeled projections both to the spinal cord and to the brainstem. In the lower brachial and upper thoracic spinal cord, bulbospinal axons traveled predominantly in the contralateral dorsolateral funiculus and terminated in close relation to the dendrites of inspiratory motoneurons retrogradely labeled with cholera toxin B-chain. In the brainstem, there were predominantly ipsilateral projections to the nucleus retroambigualis, tracheosyringeal motor nucleus (XIIts), ventrolateral nucleus of the rostral medulla, infraolivary superior nucleus, ventrolateral parabrachial nucleus, and dorsomedial nucleus of the intercollicular complex. In all these nuclei, except XIIts, retrogradely labeled neurons were also found, indicating reciprocity of the connections. These results suggest the possibility of monosynaptic connections between inspiratory premotor neurons and inspiratory motoneurons, which, together with connections of IR neurons with other brainstem respiratory-vocal nuclei, seem likely to mediate the close coordination that exists in birds between the vocal and respiratory systems. The distribution of IR neurons in birds is similar to that of the rostral ventral respiratory group (rVRG) in mammals.