Current clinical issues on mycoses in neutropenic patients

Invasive fungal infections, which are associated with high morbidity and mortality rates, are an increasing challenge for the management of immunocompromised hosts, particularly neutropenic cancer patients. Due to the ageing population, recent progress in cancer therapy and better prognosis of bacterial infections, the numbers of patients at risk of life-threatening mycoses are increasing. The percentage of cancer patients with evidence of an invasive fungal infection ranges from approximately 5% to 30%. The most common opportunistic fungal pathogens are Candida spp. and Aspergillus spp. but recently unusual pathogens including Fusarium, Trichosporon and many others have been increasingly reported. Although some progress has been made in the last decade, several controversial issues need to be addressed by clinicians as well as by medical microbiologists and mycologists involved in the care of patients experiencing fungal infections. A comprehensive clinical strategy, such as that initiated under the auspices of EORTC is a meaningful approach to ensure high quality clinical research in that field in order to define guidelines for more effective diagnosis, prevention and treatment approaches of invasive fungal infections in cancer patients at the European level.     

Syntheses and in vitro evaluation of water-soluble "cationic metalloporphyrin-ellipticine" molecules having a high affinity for DNA

The synthesis of hybrid "cationic metalloporphyrin-intercalator" molecules is reported. These molecules are based on 9-methoxyellipticine as intercalator and tris-(4-N-methylpyridiniumyl)metalloporphyrins having a 4-aminophenyl or a 4-hydroxyphenyl group for the attachment of the linker. The effect of the length of linker (7-13 bonds), the chemical nature of the linking group (with a carboxamido or an ether function), the position of amino group between the two parts of hybrid molecules, the number of intercalator moieties (ellipticinium) covalently attached to the metalloporphyrin, and the nature of the central metal atom (Mn, Fe, Zn) on the biological activity of these hybrid molecules were studied. In addition, these molecules have a high affinity for double-stranded DNA (affinity constant of hybrid molecule 9Mn,Me = 2.3 x 10(9) M-1 for poly[d(A-T)] and 2.8 x 10(8) M-1 for poly[d(G-C)] and are cytotoxic against murine leukemia cells L1210 in vitro (IC50 of 9Mn,Me = 0.8 microM). Their cytotoxicities are dependent on the nature of central atom. Iron derivatives are less active than manganese analogues and the corresponding zinc derivatives are nearly inactive despite their same affinity for nucleic acids. These highly water-soluble hybrid molecules could be considered as efficient bleomycin models based on a cationic metalloporphyrin.     

Effects of tianeptine on spontaneous alternation, simple and concurrent spatial discrimination learning and on alcohol-induced alternation deficits in mice

The effects of systemic administration of tianeptine, a new psychotropic agent with antidepressant properties, were investigated on spontaneous alternation behavior, and on simple and concurrent spatial discrimination, in normal mice of the BALB/c strain. Tianeptine increased rates of spontaneous T-maze alternation, facilitated retention of a T-maze left-right discrimination, and speeded up acquisition of concurrent discrimination in a radial maze. These effects were consistent across successive experiments with a dose of 10mg/kg; lower doses (2.5 and 5.0mg/kg) had less or no effect depending on the task. These results, together with theoretical considerations, led us to investigate the effect of tianeptine on the sequential-specific alternation deficit induced by long-term ethanol administration in the same strain of mice. Results showed that, at the dose of 10mg/kg, the drug completely alleviated the alcohol-induced deficit. Unlike tianeptine, fluoxetine impaired discrimination performance in the radial maze. These data are discussed in light of the effects of tianeptine on serotonergic transmission and of the role of serotonin and acetylcholine in learning and memory processes.     

Malleolar fractures. Predictive factors for secondary osteoarthritis. Retrospective study of 32 cases

The authors report a series of 32 ankle fractures treated by internal fixation and reviewed with a follow-up of more than 15 years. The series includes 12 fibular, 14 bimalleolar and 6 trimalleolar fractures. Following Weber's classification, there were 4 type A, 18 type B and 10 type C fractures. The postoperative x-ray showed 28 anatomy reductions; shortening of the fibula from 3 to 5 mm was noted in 4 cases. Clinical results were evaluated according to Kitaoka's criteria, and radiological results according to Magnusson's criteria. Statistical analysis was made with a Chi-square test. The retrospective review at an average follow-up of 15 years showed 19 painfree ankles, normal mobility in 22 cases, absence of edema in 18. The shoe-wear was normal in 30 cases. Walking had returned to normal in 23 cases but radiography showed narrowing of the tibiotalar joint line in 12 cases and lengthening of the medial malleolus in 16. Narrowing of the tibiotalar joint space was associated with lengthening of the medial malleolus in 10 cases. The objective results were rated as follows: 23 good, 8 fair, and 1 poor. With a follow-up of 15 years, we noted degenerative changes in the ankle in 37% of cases in spite of an anatomic reconstruction which had been perfect in 28. Shortening of the fibula, observed in 4 cases, was associated with subsequent ossification below the medial malleolus corresponding to avulsion of the non sutured medial collateral ligament. Nevertheless, degenerative changes of the ankle were clinically well-tolerated. The long term result of internal fixation of malleolar fractures was good. This was achieved only through perfect restoration of the joint anatomy. Contrary to other series, non-operative repair of the medial collateral ligament was associated with long team degenerative changes and reduced mobility of the joint. We therefore now advocate surgical repair of the medial collateral ligament.     

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.     

Liver transplantation for hepatocellular carcinoma]

Hepatocellular carcinoma (HCC) is the most frequent primitive cancer of the liver. It mostly develops on cirrhotic livers. Orthotopic liver transplantation is the only treatment that definitively addresses both the metachronous occurrence risk of HCC and the underlying disease. Under Milan criteria, i.e. less than 3 nodules of 3 cm max in diameter, or 1 nodule of 5 cm maximum, OLT has been shown effective and provides with survival rates almost equal to those obtained with HCC free cirrhotic patients. In Rennes, 195 patients with early HCC on cirrhotic livers have been transplanted from January 1995 to June 2005. Global and disease free 8 years patient survival rates were 73 and 70%, respectively. These results were significantly altered when the recipient was female, the cirrhosis due to C virus and the patient of B blood group. Despite these excellent results, the principal limit to the application of transplantation for HCC remains the long period of time patients have to wait for a graft. During this period of time, growth of the tumour may drop the patient out of Milan criteria and subsequently from the waiting list. The role of chemoembolisation, liver resection and thermal ablation while the patient is waiting for a graft remains debatable.     

Wear of alumina-on-alumina total hip arthroplasties at a mean 11-year followup

The surface topography of 11 alumina-on-alumina hip arthroplasties retrieved for aseptic loosening at a mean 11-year followup was investigated. Macroscopic wear was assessed using a coordinate measuring machine. Microscopic wear features were evaluated by Talysurf analysis. Scanning electron microscopy was used to look at the alumina microstructure. Components were classified into three groups: (1) low wear with no sign of wear and average arithmetic roughness values below 0.05 microm; (2) stripe wear with a visible oblong worn area on the femoral heads and penetration rates below 10 microm/year; and (3) severe wear with a visible loss of material on both components, showing total roughness values as much as 4 microm and maximum penetrations higher than 150 microm. Alumina quality assessed by grain size measurements and porosity percentages improved progressively from 1977 to 1988. This resulted in a correlated decrease of the microscopic wear magnitude. However, on a macroscopic scale, factors responsible for either a load increase (weight, young age, and male gender) or impairment in the load distribution over the component surfaces (large grain size, nonoptimal initial cup inclination, and cup migration and/or tilting) increased the penetration rates.