[Management of native kidneys in renal transplant recipients with autosomal dominant polycystic kidney]. / Gestion des reins natifs chez les patients transplantés rénaux dans le cadre d'une polykystose rénale autosomique dominante.

Autosomal dominant polycystic kidney disease (ADPKD) is responsible for 10 % of end-stage renal failure cases in Europe and the majority of these patients will have their renal failure treated with kidney transplantation. In this context, native kidneys will have a negligible function but maybe the source of a series of complications, whether due to polycystosis or immunosuppression. These complications include urinary tract infections, renal neoplasms, high blood pressure and abdominal pain and must be managed specifically for this particular context. Native nephrectomy may also be considered to prevent these complications, but it is a serious procedure and the risk-benefit ratio must be carefully assessed. There are still no clear and consensual guidelines on the indications for this nephrectomy or on the ideal timing of it in relation to the transplant procedure. Nevertheless, a review of the various data in the literature allows us to suggest an algorithm to help the therapeutic decision.

La polykystose rénale autosomique dominante (ADPKD) est responsable de 10 % des insuffisances rénales terminales en Europe et la majorité de ces patients verront leur insuffisance rénale traitée par transplantation rénale. Dans ce contexte, les reins natifs auront une fonction négligeable, mais pourront, en revanche, être à l'origine d'une série de complications, que ce soit à la faveur de la polykystose ou de l'immunosuppression. Ces complications comprennent notamment les infections urinaires, les néoplasies rénales, l'hypertension artérielle et les douleurs abdominales. Elles doivent être prises en charge de façon spécifique à ce contexte particulier. Une néphrectomie native peut également être envisagée afin de prévenir ces complications, mais il s'agit d'une intervention lourde dont le rapport risque-bénéfice doit être soigneusement évalué. Il n'existe pas encore de directives claires et consensuelles sur les indications de cette néphrectomie ni sur le «timing¼ idéal de celle-ci par rapport à l'opération de transplantation. Cependant, une revue des différentes données de la littérature permet de proposer un algorithme aidant à la décision thérapeutique.

Exposure to psychosocial work factors in 31 European countries.

BACKGROUND: Although psychosocial work factors are recognized as major occupational risk factors, little information is available regarding the prevalence of exposure to these factors and the differences in exposure between countries. AIMS: To explore the differences in various psychosocial work exposures between 31 European countries. METHODS: The study was based on a sample of 14,881 male and 14,799 female workers from the 2005 European Working Conditions Survey. Eighteen psychosocial work factors were studied: low decision latitude (skill discretion and decision authority), high psychological demands, job strain, low social support, iso-strain, physical violence, sexual harassment, bullying, discrimination, work-family imbalance, long working hours, high effort, job insecurity, low job promotion, low reward and effort-reward imbalance. Covariates were age, number of workers in household, occupation, economic activity, self-employed/employee, public/private sector and part/full time work. Statistical analysis was performed using multilevel logistic regression analysis. RESULTS: Significant differences in all psychosocial work factors were observed between countries. The rank of the countries varied according to the exposure considered. However, some countries, especially Denmark, Netherlands and Norway, displayed a significantly lower prevalence of exposure to four factors or more, while some Southern and Eastern countries, especially Czech Republic, Greece, Lithuania and Turkey, had a higher prevalence. CONCLUSIONS: Differences in psychosocial work exposures were found between countries. This study is the first to compare a large set of psychosocial work exposures between 31 European countries. These findings may be useful to guide prevention policies at European level.

Feasibility of biweekly combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in patients with metastatic solid tumors: results of a two-step phase I trial: XELIRI and XELIRINOX.

BACKGROUND: Biweekly schedule of capecitabine combined with irinotecan (XELIRI), consecutively with irinotecan and oxaliplatin (XELIRINOX), was evaluated in patients with metastatic cancer from any solid tumors. PATIENTS AND METHODS: In this two-step phase I trial, seventeen and eleven patients were enrolled in the XELIRI and XELIRINOX stages, respectively. RESULTS: In XELIRI, a total of 136 chemotherapy cycles were administered with a median number of 8 cycles per patient (2-16). Main dose-limiting toxicities (DLT) were grade 3-4 neutropenia, with one toxicity-related death. Maximum tolerated dose (MTD) for capecitabine combined with 180 mg/m(2) of irinotecan was 3,500 mg/m(2)/day. In XELIRINOX, capecitabine starting dose was 2,500 mg/m(2)/day. Fifty-eight chemotherapy cycles were administered with a median of 4 cycles per patient (1-16). DLT included 3 grade 4 neutropenia, associated with 1 grade 3 diarrhea, and 1 grade 4 pneumopathy leading to patient death. MTD for capecitabine with 180 mg/m(2) of irinotecan and 85 mg/m(2) of oxaliplatin was 3,000 mg/m(2)/day. The recommended doses for capecitabine were 3,000 and 2,500 mg/m(2)/day D1-D7 in combination with 180 mg/m(2) of irinotecan in XELIRI, plus 85 mg/m(2) of oxaliplatin in XELIRINOX (D1 = D14), respectively. CONCLUSION: XELIRI and XELIRINOX regimens are feasible and warrant further investigation in combination with targeted therapy in metastatic colorectal cancer patients.

Contribution of material, occupational, and psychosocial factors in the explanation of social inequalities in health in 28 countries in Europe.

OBJECTIVES: To analyse the associations between socio-economic status (SES), measured using occupation, and self-reported health, and to examine the contribution of various material, occupational and psychosocial factors to social inequalities in health in Europe. METHODS: This study was based on data from the European Quality of Life Survey (EQLS) carried out in 2003. The total sample consisted of 6038 and 6383 working men and women in 28 countries in Europe (response rates: 30.3-91.2%). Each set of potential material, occupational and psychosocial mediators included between eight and 11 variables. Statistical analysis was performed using multilevel logistic regression analysis. RESULTS: Significant social differences were observed for self-reported health, manual workers being more likely to be in poor health (OR=1.89, 95% CI 1.46 to 2.46 for men, OR=2.18, 95% CI 1.71 to 2.77 for women). Strong social gradients were found for almost all potential mediating factors, and almost all displayed significant associations with self-reported health. Social differences in health were substantially reduced after adjustment for material, occupational and psychosocial factors, with material factors playing a major role. The four strongest contributions to reducing these differences were found for material deprivation, social exclusion, financial problems and job reward. Taking all mediators into account led to an explanation of the social differences in health by 78-100% for men and women. CONCLUSION: The association between SES and poor health may be attributed to differential distributions of several dimensions of material, occupational and psychosocial conditions across occupational groups. Interventions targeting different dimensions might result in a reduction in social inequalities in health.

p53 status and response to radiotherapy in rectal cancer: a prospective multilevel analysis.

The aim of this study was to evaluate, in a prospective study, the predictive role of p53 status analysed at four different levels in identifying the response to preoperative radiotherapy in rectal adenocarcinoma. Before treatment, 70 patients were staged and endoscopic forceps biopsies from the tumour area were taken. p53 status was assessed by total cDNA sequencing, allelic loss analysis, immunohistochemistry, and p53 antibodies. Neoadjuvant treatment was based on preoperative radiotherapy or radiochemotherapy. Response to therapy was evaluated after surgery by both pathologic downstaging and histologic tumour regression grade. In all, 35 patients (50.0%) had p53 gene mutations; 44.4% of patients had an allelic loss; nuclear p53 overexpression was observed in 39 patients (55.7%); and p53 antibodies were detected in 11 patients (16.7%). In the multilevel analysis of p53 status, gene mutations correlated with both nuclear protein overexpression (P < 0.0001) and loss of heterozygosity (P = 0.013). In all, 29 patients (41.4%) were downstaged by pathologic analysis, and 19 patients (29.2%) were classified as tumour regression grade 1. Whatever the method of evaluation of treatment response, no correlation between p53 alterations and response to radiotherapy was observed. Our results do not support the use of p53 alterations alone as a predictive marker for response to radiotherapy in rectal carcinoma.

Activation of dopaminergic and cholinergic neurotransmission by tachykinin NK3 receptor stimulation: an in vivo microdialysis approach in guinea pig.

The regulation of dopaminergic and cholinergic function by neurokinin-3 (NK3) receptor activation was examined in vivo in urethane-anaesthetized guinea pigs with microdialysis probes. The local application of the NK3 tachykinin receptor agonist senktide in the region of dopamine cell bodies (pars compacta of the substantia nigra and ventral tegmental area) and in the area of cholinergic cell bodies (septal area) markedly enhanced the extracellular dopamine (DA) and acetylcholine (ACh) concentration throughout their respective target areas, i.e. striatum, nucleus accumbens, prefrontal cortex for dopaminergic systems and hippocampus for cholinergic neurons. The enhancing effect of senktide on neurotransmitter release was dose dependently blocked by the selective non-peptide NK3 receptor antagonist SR142801 (0.1-1 mg/kg, i.p.), whereas its inactive S-enantiomer SR142806 (0.3-1 mg/kg, i.p.) did not exert any antagonistic activity on the effect of intranigral or intraseptal application of senktide. These results demonstrate that NK3 receptors can modulate the activity of central DA and ACh systems.

Effects of fertilizer on insecticides adsorption and biodegradation in crop soils.

Recent organic fertilizer treatments (cow manure, pig slurry, composts, or green manure) simultaneously increase insecticide adsorption onto soil and the insecticide soil persistence, indicating a mechanism of slow release of insecticide into soil by the organic matter. This occurred in sugar beet crops with aldicarb, thiofanox and imidacloprid; also, in leek, cauliflower and brussels sprouts crops with chlorpyrifos and chlorfenvinphos. In contrast, organic fertilizer treatments applied once or repeatedly in the past, have no significant influence on adsorption or persistence of insecticides; the same is observed for the old soil organic matter, when its soil concentrations change in limited ranges

[Laparoscopic surgery versus laparotomy. Comparative analysis of stress markers]. / Coelio-chirurgie comparée à la laparotomie. Analyse comparative des marqueurs du stress.

The place of laparoscopic surgery continues to increase in the field of surgery in our specialty. Although the advantages would seem to be obvious, it seemed to us interesting to quantify, if possible, the parameters of operative stress and compare laparoscopic surgery with conventional surgery. Markers studied are Prolactin, Cortisol, Adrenaline, Nor-Adrenaline, Dopamine and the Beta-Endorphins. The only marker that shows any difference in the two procedures in our study is Beta-Endorphin which is significantly less raised in laparoscopic surgery directly after the operation (p less than 0.01). This was very specific for pain, which is one of the benefits of this technique and shown in this parameter which confirms the clinical impression. The curves of the changes in the different markers have been analysed and discussed.

Spectral and enzymatic properties of human recombinant myeloperoxidase: comparison with the mature enzyme.

Human recombinant myeloperoxidase (recMPO), purified from an engineered Chinese hamster ovary (CHO) cell line, has been characterized and compared to the mature enzyme isolated from polymorphonuclear leukocytes. Both molecules appear essentially similar in physicochemical enzymatic terms according to the following observations. 1. The unprocessed recombinant protein displays the characteristic light absorption spectra of ferric mature MPO and exhibits its typical spectral changes in the presence of dithionite or hydrogen peroxide. 2. The addition of 14C-labeled 5-aminolevulinic acid, a heme precursor, to the culture medium of recombinant CHO cells yields labeled recMPO, indicating the presence of a heme-like structure in the molecule. 3. Like mature MPO, recMPO has a peroxidatic activity and catalyzes the oxidation of chloride ions in the presence of hydrogen peroxide, producing hypochlorous acid as measured by the monochlorodimedon assay. For both enzymes, the chlorinating activity optimally occurs around pH 5.0 at about 100 microM of hydrogen peroxide and is strongly inhibited by methimazole. 4. Diethylpyrocarbonate significantly reduces the enzymatic activity of both molecules, suggesting that histidine residues may be of prime importance in the active site of the enzymes. 5. According to infrared spectroscopy data, both enzymes present a very similar secondary structure organization. In conclusion, the data suggest that the processing of the precursor enzyme (recMPO) into the mature form occurs without major structural and functional consequences.

Self-labeling of human polymorphonuclear leucocyte myeloperoxidase with 125iodine.

In order to obtain a radioimmunoassay (RIA) technique for the measurement of human plasma myeloperoxidase (MPO), we purified the enzyme from polymorphonuclear granulocytes (neutrophils), and compared three methods of labeling it with 125Iodine:chloramine T, lactoperoxidase, and an original technique of 'self labeling' based on the ability of the enzyme to oxidize and bind 125I in the presence of H2O2. The chloramine T technique produced a degraded protein, as well shown by a high non-specific binding of tracer to antibody. The lactoperoxidase technique did not succeed in labeling MPO with an adequate specific activity. In contrast, the self-labeling method gave a stable tracer with a specific activity of 23 microCi/micrograms MPO (85 MBq), a satisfactory level of immunoreactivity, and a low-specific binding (less than or equal to 3%). After labeling, purification of tracer was achieved by gel filtration chromatography in phosphate buffer (0.05 M; pH7) to which 0.1% poly-L-lysine was added. The labeled molecule remained stable for 40 days and could be used for RIA with a polyclonal antibody raised in rabbits.

Fast double antibody radioimmunoassay of human granulocyte myeloperoxidase and its application to plasma.

The haem enzyme myeloperoxidase (MPO) (EC 1.11.1.7) with a spectral A430/A280 ratio greater than 0.7 and a specific activity of 125 U/mg was purified from isolated human neutrophils. To obtain a radioimmunoassay (RIA) for this enzyme, a specific antiserum against human neutrophil MPO was raised in rabbits and used at an initial dilution of 1/10,000. MPO labelled with 125iodine by a technique of self-labelling in the presence of H2O2, had a specific activity of 24 mCi/mg. After incubation at room temperature (2 h) and separation by double antibody precipitation in the presence of polyethylene glycol, the sensitivity of the RIA was 21 ng/ml. The RIA showed good precision and accuracy with intra- and interassay coefficients of variation of less than 7% for MPO concentrations ranging from 100 to 800 ng/ml, and satisfactory recoveries of known amounts of exogenous MPO in plasma. For the measurement of MPO in blood, the best sampling technique was to collect blood into EDTA. Rapid centrifugation (within 20 min) was necessary for blood collected into heparin. Mean MPO values in normal individuals were 340 +/- 98 ng/ml in EDTA plasma (n = 152) and 332 +/- 82 ng/ml in heparinized plasma (n = 34). When MPO was measured 12-6 h after injury in critically ill patients high values (above 1000 ng/ml) were found in 6/15 patients with multiple injuries. In patients with sepsis (n = 22), MPO values were always above 1000 ng/ml.

[Celioscopy with peridural anesthesia. Techniques, indications, results in 220 cases]. / La coelioscopie sous anesthésie péridurale. Techniques, indications, résultats à propos de 220 cas.

The authors used epidural anaesthesia to carry out laparoscopy in 220 patients. The chief indications for the laparoscopies were GIFT (intratubal transfer of gametes) and tubal sterilization. The technique used was slightly different according to the indications for the use but they had to be sure of anaesthetising up to T4. In 90% of cases the patients tolerated the procedure well. No change in ventilation or in metabolic measurements. As far as fertilization was concerned studies carried out in various parameters failed to show any untoward side effects due to the use of local anaesthetics. Finally so long as the anaesthesia is only used for a short length of time this technique seems to be suitable for day cases.

Human myeloperoxidase activity is inhibited in vitro by quercetin. Comparison with three related compounds.

Quercetin is an effective inhibitor of human myeloperoxidase (MPO) activity, both with purified enzyme (IC50 = 3.5 microM) and in a system using stimulated human neutrophils. Quercetin is significantly more potent than three other related compounds (rutin, rutin sulfate and troxerutin) and than methimazole, a previously-known myeloperoxidase inhibitor. The inhibitory activity of quercetin is of the competitive type. Moreover, quercetin is directly able to scavenge hypochlorous acid (HOCl), a chlorinated species generated by the MPO/H2O2/Cl- system.

Ginkgo biloba extract inhibits oxygen species production generated by phorbol myristate acetate stimulated human leukocytes.

A Ginkgo biloba extract (Gbe) containing flavonoids, among other compounds, was tested for the release of activated oxygen species (O-2, H2O2, OH.) during the stimulation of human neutrophils (PMNs) by a soluble agonist. The extract slows down O2 consumption (respiratory burst) of stimulated cells by its inhibitory action on NADPH-oxidase, the enzyme responsible for the reduction of O2 to O-2. Consequently, superoxide anion (O-.2) and hydrogen peroxide (H2O2) production is significantly decreased when the PMNs stimulation is done in the presence of the extract at concentrations of 500, 250 and 125 micrograms/ml. Moreover, the hydroxyl radical generation (OH.) is very much decreased at concentrations as low as 15.6 micrograms Gbe/ml, which indicates that the extract also has free radical scavenging activity. Gbe is able at least to reduce very severely the activity of myeloperoxidase contained in neutrophils. This enzyme, secreted into the intra and extracellular medium, catalyzes the oxidation of chloride (Cl-) by H2O2 to yield strong oxidants (HOCl, chloramines) which are implicated in inflammatory processes.

Stimulation of cyclooxygenase by activated human neutrophils is enhanced by uric acid.

Activated human neutrophils supernatant enhances prostanoids production by bull seminal cyclooxygenase (455% of control). Superoxide anion and hydrogen peroxide are not involved in this stimulation, in these experimental conditions. Myeloperoxidase (by its hemic nature) and HPETEs (by their -OOH function) could trigger cyclooxygenase. In the presence of uric acid (10(-3) M), a potent hydroxyl radical scavenger, the cyclooxygenase stimulation by supernatant is increased until 709% of the control.

Casein and other tumor markers in relation to cancer of the breast.

Five tumor markers can be simultaneously determined in the serum by radioimmunoassay: carcinoembryonal antigen (CEA), alpha-fetoprotein (alpha-FP), human chorionic gonadotropin (HCG), beta-subunit of HCG (beta-HCG) and kappa-casein. In a series of 935 healthy subjects, these antigens remain detectable or are detected within very precise limits. At the start of the clinical evolution of breast cancer, the incidence of pathological concentrations is increased as compared with the highest level observed in normal subjects. This high incidence is mainly due to a concomitant determination of CEA, kappa-casein, HCG and beta-HCG. The alpha-FP test is never positive, while the kappa-casein concentration is particularly high in the first clinical stages of breast cancer and with metastases. The concomitant determination of these tumor markers may be a biological element contributing to the diagnosis of neoplasia, although it is neither an absolute nor a specific criterium. Indeed, a pathological concentration of at least one antigen was observed in 5.5% of the subjects presenting with benign mastopathy. When metastases occur (25 patients), the incidence of pathological concentrations of at least one antigen increases: 88%, the absolute values of these levels increasing simultaneously. The determination of the antigen concentration therefore allows an evaluation of the extension of the disease. Surgical removal reduces the incidence of positivity of these antigens to 34%. Persistence of pathological levels seems to be related to a possibility of relapse or metastatic spreading. Finally, chemotherapy and radiotherapy applied on a tumor which is not excised, does not decrease the incidence of positivity of the tumoral markers, although their levels seem to fluctuate with the clinical evolution.