[Intervention of psychological and ethical professionals of human science in obstetrical morbidity and mortality conferences]. / L'intervention des sciences humaines en psychologie et en éthique dans les revues de morbi-mortalité en obstétrique.

OBJECTIVE: To identify the defence mechanisms manifested by medical staff which could disturb the decision making, revealed by professionals of human science (PHS) in morbidity and mortality conferences (MMC). MATERIALS AND METHODS: Application of two methods of psychological intervention in MMC, conducted between March 1st, 2009 and November 30, 2010, in 20 randomized maternity among five perinatal networks: the method of inter-active problem solving targeted at the functioning of the teams and the method for developing professional practice centred on individual. The data collection was realized during analyse of case in MMC, with note-taking by two pair PHS. The oral expressions of RMM' participant were secondarily re-written, analyzed and classed by theme. RESULTS: Fifty-four MMC were performed. The mechanisms of defence have been identified by PHS intervention in MMC: denial of situation, pact of denegation, rift and overprotection. They were be identified by two PHS intervention methods, this consolidates these results. This intervention began staff medical to transformation at different level, in particular to improve the capacity of cooperation. CONCLUSION: The identification of the mechanisms of defence in MMC enables staff medical to improve communication and quality relationship between healthcare professionals. This could constitute an actual factor of practices improvement. However, complementary studies must be performed to confirm this hypothesis.

The distribution of tritium in the terrestrial and aquatic environments of the Creys-Malville nuclear power plant (2002-2005).

The Creys-Malville nuclear plant, located on the left bank of the Rhône, was shut down in 1998. The facilities are currently in their initial stage of dismantling. In order to establish a baseline for tritium in the vicinity of the site prior to the main dismantling phase, we carried out a monitoring program between 2002 and 2005 in the main terrestrial and aquatic compartments of the local environment. Tritium levels in the groundwaters and in the Rhône waters correspond to the regional tritium concentration in precipitation. The data obtained for the terrestrial environment are also in good agreement with the regional background and do not show any specific signature linked to the nuclear plant. The various aquatic compartments of the Rhône (fish, plant, sediment) are significantly enriched in tritium both upstream and downstream of the power plant: although Tissue-Free Water Tritium concentrations are in equilibrium with the river water, the non-exchangeable fraction of organic bound tritium in plants and fishes shows values which outpace the river water background by one to two orders of magnitude, and up to four to five orders of magnitude in the sediments. This tritium anomaly is not related to the nuclear plant, as it is already present at the Swiss border 100km upstream of the site. Although fine particles of tritiated polystyrene entering the composition of the luminous paints used by the clock industry have been suspected on several occasions, the exact nature and the origin of this tritium source remain unknown and require further investigations.

Chromosomal abnormalities in women with breast cancer after autologous stem cell transplantation are infrequent and may not predict development of therapy-related leukemia or myelodysplastic syndrome.

We determined prospectively the incidence of chromosomal abnormalities in patients with high-risk breast cancer (HRBC) after high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT), and correlated the cytogenetic abnormalities with the development of post-transplant myelodysplastic syndrome or acute myeloid leukemia (MDS/AML). From 1990 to 1999, 229 women with HRBC underwent ASCT. Cytogenetic analysis of bone marrow (BM) cells was performed 12-59 months after ASCT in 60 consecutive women uniformly treated with six courses of FAC/FEC followed by HDCT and ASCT. With a median follow-up of 36 months after ASCT, there were no cases of MDS/AML among the 229 patients. In the selected cohort of 60 patients, three (5%) showed clonal chromosomal abnormalities (two single trisomy X and one t(1;6)), whereas two additional patients showed non-clonal reciprocal translocations. Two of the patients with clonal aberrations had blood cytopenias as well as subtle dysplastic pictures in BM which were not classifiable as MDS according to the FAB criteria. Similar dysplastic features were also observed in four patients with normal karyotypes. All cytogenetic aberrations were transient and disappeared, except a +X detected by FISH in a residual cell population in one of the patients. Retrospective cytogenetic and FISH studies of samples obtained after six cycles of FAC/FEC and before transplant demonstrated no chromosomal abnormalities in any of the five patients with post-ASCT karyotypic changes. Early changes in karyotype detected in breast cancer patients following ASCT are transient and do not correlate with or predict development of MDS/AML. As these aberrations were not present before ASCT, they may be related to the HDCT regimen or transplant procedure rather than to the prior adjuvant therapy. Our results suggest that ASCT may be less likely to cause MDS or AML in breast cancer patients as compared to other malignancies. Bone Marrow Transplantation (2000) 25, 1203-1208.

Choroidal readaptation to gravity in rats after spaceflight and head-down tilt.

To determine when choroidal structures were restored after readaptation to Earth gravity or orthostatic position, fine structure and protein distribution were studied in rat choroid plexus dissected either 6 h [Space Life Sciences-2 (SLS-2) experiments] or 2 days [National Institutes of Health-Rodent 1 (NIH-R1) experiments] after a spaceflight, or 6 h after head-down tilt (HDT) experiments. Apical alterations were noted in choroidal cells from SLS-2 and HDT animals, confirming that weightlessness impaired choroidal structures and functions. However, the presence of small apical microvilli and kinocilia and the absence of vesicle accumulations showed that the apical organization began to be restored rapidly after landing. Very enlarged apical microvilli appeared after 2 days on Earth, suggesting increased choroidal activity. However, as distributions of ezrin and carbonic anhydrase II remained altered in both flight and suspended animals after readaptation to Earth gravity, it was concluded that choroidal structures and functions were not completely restored, even after 2 days in Earth's gravity.

Changes in apical organization of choroidal cells in rats adapted to spaceflight or head-down tilt.

Structural changes observed in choroid plexuses from rats dissected aboard a space shuttle, on day 13 of an orbital flight (NASA STS-58 mission, SLS-2 Experiments) demonstrated that choroidal epithelial cells display a modified organization in a microgravitational environment. Results were compared with ultrastructural observations of choroid plexus from rats maintained under anti-orthostatic restraint (head-down tilt) for 14 days. In both experiment types, the main alterations observed by transmission electron microscopy, at the level of choroidal epithelial cells from the third and fourth ventricles, concerned the formation and the organization of apical microvilli, whereas pseudopod-like structures appeared. Immunocytochemical distribution of ezrin, a cytoskeletal protein involved in apical cell differentiation in choroid plexus, confirmed the structural alteration of microvilli in head-down tilted rats, Kinocilia tended to disappear from the apical surface, suggesting a partial loss of cell polarization. In addition, large amounts of clear vesicles were gathered in the apical cytoplasm of choroidal epithelial cells. Disorganization of apical microvilli accumulations of apical vesicles and partial loss of cell polarity showed that long-stays in weightlessness induced alterations in the fine structure of choroid plexus, consistent with a marked reduction of cerebrospinal fluid production.

Choroidal responses in microgravity. (SLS-1, SLS-2 and hindlimb-suspension experiments).

Fluid and electrolyte shifts occurring during human spaceflight have been reported and investigated at the level of blood, cardiovascular and renal responses. Very few data were available concerning the cerebral fluid and electrolyte adaptation to microgravity, even in animal models. It is the reason why we developed several studies focused on the effects of spaceflight (SLS-1 and SLS-2 programs, carried on NASA STS 40 and 56 missions, which were 9- and 14-day flights, respectively), on structural and functional features of choroid plexuses, organs which secrete 70-90% of cerebrospinal fluid (CSF) and which are involved in brain homeostasis. Rats flown aboard space shuttles were sacrificed either in space (SLS-2 experiment, on flight day 13) or 4-8 hours after landing (SLS-1 and SLS-2 experiments). Quantitative autoradiography performed by microdensitometry and image analysis, showed that lateral and third ventricle choroid plexuses from rats flown for SLS-1 experiment demonstrated an increased number (about x 2) of binding sites to natriuretic peptides (which are known to be involved in mechanisms regulating CSF production). Using electron microscopy and immunocytochemistry, we studied the cellular response of choroid plexuses, which produce cerebrospinal fluid (CSF) in brain lateral, third and fourth ventricles. We demonstrated that spaceflight (SLS-2 experiment, inflight samples) induces changes in the choroidal cell structure (apical microvilli, kinocilia organization, vesicle accumulation) and protein distribution or expression (carbonic anhydrase II, water channels,...). These observations suggested a loss of choroidal cell polarity and a decrease in CSF secretion. Hindlimb-suspended rats displayed similar choroidal changes. All together, these results support the hypothesis of a modified CSF production in rats during long-term (9, 13 or 14 days) adaptations to microgravity.

[Randomized trial of initial chemotherapy with cisplatin alone or in combination in 241 advanced carcinomas of the upper respiratory and digestive tract]. / Essai randomisé de chimiothérapie initiale par cisplatine seul ou associé dans 241 carcinomes étendus des voies aéro-digestives supérieures.

Two hundred and forty-one patients, with advanced squamous cell carcinoma of head and neck, were randomized to receive three courses of induction chemotherapy. The chemotherapy regimens were delivered every 3 weeks, and consisted in 1) cisplatin, 80 mg/m2 given alone (CDDP regimen), or 2) in combination with vincristine, 1 mg, d 1, methotrexate 10 mg/m2 d 1, 2, 3, and bleomycin 10 mg/m2, d 1, 2, and 3 (MOB-P). Tolerance was significantly better with the CDDP regimen (p less than 0.05); severe side effects, affecting mainly digestive tract, and bone marrow, were encountered in 7% of the patients in the CDDP group, vs 15% in the MOB-P group, without death related to pancytopenia. Short-term results were better for patients treated by the MOB-P regimen, with a 42% response rate (including 9 complete responses) vs 22% with the CDDP regimen (p = 0.01). A superiority of combination chemotherapy was more significant for primary sites than regional lymph nodes. The relapse-free survival was not statistically different in the 2 groups, as well as the 2 years overall survival. Among responders, the survival was found highly correlated with a good initial general status (p less than 0.01), and with the highest total doses of cisplatin (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

[A randomized study comparing cisplatin alone or combined in the palliative treatment of carcinoma of the head and neck. Analysis of a series of 209 patients]. / Etude randomisée comparant le cisplatine seul ou associé dans le traitement palliatif de carcinomes des voies aéro-digestives supérieures. Analyse d'une série de 209 patients.

Two hundred and nine patients, with locoregional or metastatic recurrences of head and neck epidermoid carcinoma, were randomized to receive a palliative chemotherapy. The chemotherapy regimens were delivered every 3 weeks, and consisted in (1) cisplatin, 80 mg/m2 given alone (CDDP regimen), or (2) in combination with vincristine, 1 mg, methotrexate 10 mg/m2 d 1, 2, 3, and bleomycin 10 mg/m2, d 1, 2 and 3 (1040 regimen). Short-term results were better for patients treated by the 1040 regimen, with a 30% response rate (including 4 complete responses) vs 15% with the CDDP regimen (P = 0.01). A superiority of combination chemotherapy was found for all tumoral sites, but was particularly significant for pulmonary and cutaneous metastases, in previously un irradiated areas (P = 0.001). Tolerance was significantly better with the CDDP regimen (P = 0.001); severe side effects, affecting mainly general status, digestive tract and bone marrow were encountered in 5% of the patients in the CDDP group, vs 21% in the 1040 group, with one death related to pancytopenia. The median duration of remissions was not statistically different in the 2 groups, as well as the 2 years overall survival. Among responders, the survival was slightly better in those treated with CDDP alone; moreover, the quality of long term results was found highly correlated with a good initial general status, and with low levels of side effects. Those results confirm recent data of the literature, and lead to the following conclusions: (1) combination chemotherapy with CDDP give a better response rate than CDDP alone, (2) response rate doesn't influence overall duration of survival, (3) tolerance to treatment is crucial to preserve quality of life, and thus, (4) palliative chemotherapy in head and neck cancer should be efficient but also as short of intensity as possible.

[Metastatic malignant thymoma]. / Thymomes malins métastatiques.

Three cases of metastatic malignant thymoma are reported. In all three cases the tumour was invasive and excision was only partial or impossible. Histologically, these tumours were of epithelial origin with a variable lymphocytic component. Metastases were initially present in one case and in the other two developed within the first year. Partial remission was obtained with different drug combinations in only one case, and it was of short duration. The authors emphasize the increased frequency and poor prognosis of these tumours and the need for multiple chemotherapy and loco-regional treatment in the management of invasive thymomas.

[Treatment of hypercalcemia in osteolytic metastases with oral amino-hydroxypropylidene-diphosphonate]. / Traitement des hypercalcémies des métastases ostéolytiques par l'amino-hydroxypropylidène-diphosphonate par voie orale.

Twelve patients with malignant hypercalcemia were treated with amino-hydroxypropylidene-diphosphonate (APD), a potent inhibitor of osteoclast-mediated bone resorption. The mean serum calcium levels fell from 3,48 +/- 0,27 mmol/l before treatment to 2,66 +/- 0,31 after 10 days of oral APD (10 to 15 mg/kg/d) as the sole agent (p less than 0,001). The molar calcium/creatine ratio in the 24-h urine was significantly reduced from 2,11 +/- 0,73 to 0,70 +/- 0,52 after ten days of treatment (p less than 0,001). Serum phosphorus and urine hydroxyproline did not change significantly. Tolerance was good except for two patients with hiatal hernia who developed oesophagitis. Ours results confirm that oral APD is an effective and simple treatment of malignant hypercalcemia.

[Acute lymphoblastic leukemia secondary to Ewing's sarcoma treated by a combination of surgery-radiotherapy-chemotherapy]. / Leucémie aiguë lymphoblastique secondaire à un sarcome d'Ewing traité par association chirurgie-radiothérapie-chimiothérapie.

An acute lymphocytic leukaemia develops in a fourteen years old boy, treated five and a half years earlier for an Ewing's sarcoma of the right fibula, by an association of surgery, radiotherapy and chemotherapy. The Ewing's sarcoma is still in remission. Chemotherapy induces easily a complete remission. The authors discuss the links between the two malignancies and their treatment.

Cancer treatment by methotrexate: rational use following pharmacokinetic study.

We used the test-dose method to calculate the dose of methotrexate to administer to the patients to reach the therapeutic but non-toxic blood concentration of 10(-5) mol/L. Methotrexate was tested with a radioimmunoassay technique and in 19 out of 20 patients we obtained the desired plateau during 24-h infusion.

[Place of hormone receptor determination in the therapeutic strategy of breast cancer]. / Place de la détermination des récepteurs hormonaux dans la stratégie thérapeutique des cancers du sein.

Up to the discovery of hormonal receptors it was somewhat uncertain to prescribe hormonotherapy for the treatment of a breast cancer. The presence of estrogen receptors (ER) and progesterone receptors (PR) allows the estimation of the probability of hormone-dependence. The response to endocrine therapy will be expected with a rate of: 80% of the tumors PR +; 30% of the tumors ER+ but PR-; 10% of the tumors ER - and PR -. The response to chemotherapy is no accurately correlated with the concentration of receptors. The planning of therapy will be founded on the following principles. ER -: less favourable prognosis and unlikely response to endocrine therapy, therefore chemotherapy if the other prognostic factors are bad. ER +: endocrine therapy is required, especially if PR +. The role of chemotherapy ought to be discussed with respect to the other prognostic factors. All these factors are reviewed and a decision-tree of the treatment of advanced breast cancers is put forward. In short, it is obvious that the receptors assays have to be carried out as for as possible.

[Cardiac risks of adriamycin. Early detection of high-risk patients by isotopic cardiac function study]. / Risque cardiaque de l'adriamycine. Repérage précoce des sujets á haut risque par l'étude fonctionnelle cardiaque isotopique.

Adriamycin is known to be effective in the treatment of breast cancer. Serial radionuclide determinations of the left ejection fraction can provide advanced warning of adriamycin cardiotoxicity, prior to clinical signs of the left ventricular dysfunction. Patients at high risk of congestive heart failure can be detected. Depending on the results of the second course of chemotherapy, guidelines and criteria can be laid down to predict the appropriate time for drug discontinuation.

[Proposal for a surgical evaluation index card for ovarian cancers]. / Proposition d'une "fiche de bilan chirurgical" des cancers de l'ovaire.

The authors propose a computer card for registering the main information required in the management of ovarian cancers. The data include a detailed description of the lesions noted at operation, the surgical procedure, and postoperative lesions. They concern both the initial laparotomy and any second-look operations.

[Complications of antitumor and antileukemia chemotherapy. 3 (conclusion)]. / Accidents de la chimiothérapie antitumorale et antileucémique. Troisième partie (fin).

Among the neurological side-effects, peripheral neuropathy is a result of therapy with vindesine and above all vincristine. Although in most cases it is responsible only for paresthesias, it may cause extensive paralysis and requires that the drug be discontinued. These drugs may also affect the neurovegetative system. Ototoxicity may be seen with cis-platinum and vigilance disturbances with L-asparaginase. Genetic consequences are mainly due to alkylating agents. These agents almost constantly impair male and female fertility but recovery is possible. Libido is also affected with the attendant psychological consequences. The offspring of patients previously treated by chemotherapeutic agents are normal. Development of secondary carcinoma or leukemia is currently a major concern. Secondary malignant disease may develop after the treatment of any cancer, especially if radiotherapy was associated with alkylating agents. Leukemias are of the acute myeloid type and usually follow a preleukemic phase. A table summarizes the main toxicities of the most usual drugs.

[Complications of antitumor and antileukemic chemotherapy. 1]. / Accidents de la chimiothérapie antitumorale et antileucémique. Première partie.

The recent development of chemotherapy in the treatment of cancer and leukemia requires that all practitioners involved have a thorough knowledge of the sometimes life-threatening side-effects of chemotherapeutic agents. All these agents, whether used alone or in a combination, carry a risk because of their lack of specificity which make active on normal cells, especially those with a rapid turn-over such as the hematopoietic cells or the cells of the digestive tract. Prior to the prescription of a chemotherapeutic regimen, the acceptable risk must always be clearly defined, according to the seriousness of the disease and to the patient's age, physical condition and psychological status. During the course continuous monitoring adjusted to the specific toxicity of the agents used is requisite. More or less prominent asthenia and weight loss are common, as the result of various physiopathological mechanisms. Digestive disorders may consist only of nausea and emesis or include mucosal lesions with diarrhea as the main feature. Vincristine and vindesine are responsible for constipation. Hepatic toxicity, which is less common, is usually due to L-asparaginase. Transient hair loss is the most frequent cutaneous side-effect. Hyperpigmentation, photosensitivity, nail lesions, cellulitis and ulcerations may occur, as well as specific lesions with bleomycin. High fever during injection often occurs with this last agent.

[Adverse effects of antitumor and antileukemic chemotherapy. 2]. / Accidents de la chimiothérapie antitumorale et antileucémique. Deuxième partie.

Aplastic anemia is the most severe hematologic side-effect. All chemotherapeutic agents, with the exception of bleomycin and L-asparaginase, may induce aplasia, but the degree of hematotoxicity varies according to the drug. With the exception of acute leukemia in which drug-induced aplasia is part of the treatment, aplasia must be prevented through perfect knowledge of the posology and injection schedules for each drug, as well as by adjusting doses to the patient's hematological status. If aplasia develops, intensive hematological care is requisite. The most common cardiac side-effect is toxic cardiomyopathy caused by anthracyclines, which must be diagnosed early by EKG recordings before each injection and repeated ultrasonography or dynamic cardiac scintigraphy. The risk of toxic cardiomyopathy makes it requisite not to exceed the maximal doses set for each drug. Pulmonary side-effects include acute hypersensitivity pneumopathy and chronic diffuse interstitial fibrosis, the latter being more common and mainly caused by bleomycin. The risk of chronic fibrosis demands that patients be closely monitored and that the total dose be kept under 300 mg. Renal toxicity usually results in acute transient renal failure, as with cisplatinum, and requires a thorough biological study before each injection. Vesical hemorrhage, which is threatening in some instances, may occur with cyclophosphamide. VM26 and VP16 may induce anaphylactic shock. Allergic symptoms are possible with L-asparaginase and bleomycin.