Indigenous food ingredients for complementary food formulations to combat infant malnutrition in Benin: a review.

This paper reviews indigenous Beninese food resources as potential ingredients for complementary infant foods with the aim to develop affordable formulations for low-income households in each agro-ecological zone of the country. Potential ingredients were selected on their documented nutritional value. The selected foods encompass 347 food resources, namely 297 plant products from home gardens or collected from natural vegetation and 50 animals, either domesticated or from the wild. The compiled data reveal that the distribution of the available food resources was unbalanced between agro-ecological zones. Only a few animal ingredients are obtainable in northern Benin. Most resources are seasonal, but their availability may be extended. A high variation was observed in energy and nutrient contents. Antinutritional factors were identified in some resources, but processing techniques were reported to reduce their presence in meals. In general, ingredients from local tree foods (Adansonia digitata, Parkia biglobosa) were adequate as sources of nutrients for complementary infant foods. Based on this review, local foods for the development of complementary food formulas for Beninese infants and children may be selected for each agro-ecological zone. The approach used is exemplary for other sub-Saharan African countries in need of complementary infant foods. © 2017 Society of Chemical Industry.

Structure-driven nonlinear instability as the origin of the explosive reconnection dynamics in resistive double tearing modes.

The onset of abrupt magnetic reconnection events, observed in the nonlinear evolution of double tearing modes (DTM), is investigated via reduced resistive magnetohydrodynamic simulations. We have identified the critical threshold for the parameters characterizing the linear DTM stability leading to the bifurcation to the explosive dynamics. A new type of secondary instability is discovered that is excited once the magnetic islands on each rational surface reach a critical structure characterized here by the width and the angle rating their triangularization. This new instability is an island structure-driven nonlinear instability, identified as the trigger of the subsequent nonlinear dynamics which couples flow and flux perturbations. This instability only weakly depends on resistivity.

Therapy-related acute promyelocytic leukemia: a report on 16 cases.

PURPOSE: To analyze the type of prior tumor and treatment in therapy-related acute promyelocytic leukemia (tAPL) that occurs after chemotherapy and/or radiotherapy (RT), and the hematologic characteristics and outcome of tAPL. PATIENTS AND METHODS: Sixteen patients with tAPL who were gathered during a 10-year period (1982 to 1991) in seven hematologic centers were analyzed retrospectively. RESULTS: There were 13 women and three men. The median age was 46 years (range, 12 to 82). Prior tumor was breast carcinoma in 10 cases, another solid tumor in three cases, and lymphoma in three cases. Two patients had received RT alone, and 14 had received chemotherapy (with RT in 11 cases). Prior chemotherapeutic agents generally included a combination of cyclophosphamide (used for limited periods), fluorouracil (5-FU), vinca alkaloids, and doxorubicin, mitoxantrone, or etoposide (VP16). By contrast, alkylating agents other than cyclophosphamide had been used in only two patients. Median interval between onset of treatment for the prior tumor and diagnosis of APL was 25 months. No patient had a known preleukemic phase. Hematologic and cytogenetic characteristics of the cases of tAPL were identical to those of the usual de novo APL, which included the presence of t(15; 17) in nine of the 10 patients tested. Two patients had early death. Seven patients were treated with intensive chemotherapy, and six achieved complete remission (CR). Three of them subsequently relapsed. Seven patients were treated with all-trans-retinoic acid (ATRA), and four achieved CR through the differentiation of blasts into mature granulocytes. None has relapsed so far. CONCLUSIONS: Our findings suggest that tAPL is not exceptional, and usually has several features in common with other types of therapy-related AML with specific karyotype (ie, t(8;21),t(9;11), inv(16)): solid tumor rather than hematologic malignancy as primary tumor, short interval of development, absence of known preleukemic phase, prior chemotherapy with a combination of several drugs that often included an agent that targets topoisomerase II (doxorubicin or mitoxantrone, but less often VP16). Hematologic characteristics and response to therapy (intensive chemotherapy or ATRA) in tAPL do not seem to differ from those of de novo APL.

High-dose sequential chemotherapy with recombinant granulocyte colony-stimulating factor and repeated stem-cell support for inflammatory breast cancer patients: does impact on quality of life jeopardize feasibility and acceptability of treatment?

PURPOSE: This study was designed to investigate the quality of life (QOL) of patients enrolled onto the High-Dose Chemotherapy for Breast Cancer Study Group trial (PEGASE 02), a French pilot multicenter trial of the treatment of inflammatory breast cancer (IBC) aimed at evaluating (1) toxicity and feasibility of sequential high-dose chemotherapy (HDC) with recombinant human granulocyte colony-stimulating factor (filgrastim) and stem-cell support and (2) response to HDC in terms of pathologic response and survival. PATIENTS AND METHODS: QOL measures were performed at inclusion and four times subsequently up to 1 year using an ad hoc side-effect questionnaire (19 physical symptoms) and the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30). RESULTS: Of the 95 patients entered, the overall QOL questionnaire completion compliance was 75.6%. During cycle 3 of HDC, the number of symptoms was high (mean +/- SD QOL score, 10 +/- 3), with fatigue, hair loss, appetite loss, nausea, change in taste, vomiting, fever, and weight loss reported by more than 60% of patients. Toxicity and distress associated with HDC were reflected in the decline of four EORTC QLQ-C30 scores: global QOL (P =.001), and physical, role, and social functioning (P <.001 for all statistics). However, QOL deterioration disappeared after treatment completion, except for physical functioning (P =.025). One year after inclusion, most QOL scores returned to baseline, and both emotional functioning and global QOL scores were even higher than baseline (P =.030 and P =.009, respectively). CONCLUSION: If it is confirmed that improvements in pathologic response rates with HDC effectively translate into increased probabilities of survival for IBC patients, adoption of such treatment as PEGASE 02 will not involve crucial choices between length of life and QOL and should not be delayed for QOL arguments.

Randomized, controlled, dose-range study of Ro 25-8315 given before and after a high-dose combination chemotherapy regimen in patients with metastatic or recurrent breast cancer patients.

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25-8315) on progenitor cell mobilization and hematologic recovery in cancer patients. PATIENTS AND METHODS: Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part II) chemotherapy either a single-dose injection of Ro 25-8315 (20 microg/kg, n = 9; 60 microg/kg, n = 9; 100 microg/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 microg/kg/d; part II, 5 microg/kg/d) (control group, n = 8). RESULTS: Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 microg/kg. The peak of circulating CD34(+) cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 x 10(9)/L by day +15. In part II, high levels of circulating CD34(+) cells (> 20 cells/microL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 x 10(9)/L) was similar in the four groups. Ro 25-8315 100 microg/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 x 10(9)/L on day +12 after chemotherapy. CONCLUSION: A single injection of Ro 25-8315 100 microg/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 microg/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 25-8315 should be determined according to the planned chemotherapy regimen.

Tamoxifen adjuvant treatment duration in early breast cancer: initial results of a randomized study comparing short-term treatment with long-term treatment. Fédération Nationale des Centres de Lutte Contre le Cancer Breast Group.

PURPOSE: In 1986, The Fédération Nationale desCentres de Lutte Contre le Cancer Breast Group initiated a multicenter randomized trial to assess the usefulness of long-term adjuvant tamoxifen treatment. Short-term adjuvant tamoxifen treatment was to be compared with life long adjuvant tamoxifen treatment. PATIENTS AND METHODS: Patients who were disease-free after 2 to 3 years of adjuvant tamoxifen treatment were eligible for the trial. From September 1986 to May 1995, 3,793 patients were randomized from France, Belgium, and Argentina. A total of 1,882 patients stopped tamoxifen (short-term group), and 1,911 patients were to continue tamoxifen for life (long-term group) at the same dose as previously prescribed. The protocol was modified in February 1997, limiting tamoxifen treatment to 10 years after randomization, thus giving a comparison between a 2- to 3-year treatment and a 12- to 13-year treatment. To date, the median duration of tamoxifen treatment is 30 months in the short-term group, and 70 months in the long-term group. RESULTS: Overall, longer tamoxifen treatment induced a 23% reduction in relapse rates, leading to a 7-year disease-free survival rate of 78%, compared with 72% in the shorter-treatment group. In contrast, overall survival did not differ between the two groups, with a 79% overall survival rate in both groups. This improvement in disease-free survival could be observed in node-positive patients (P: =.001); however, it was not found in node-negative patients. Prolonged tamoxifen treatment corresponded to a significant increase in disease-free survival in estrogen receptor-positive patients (P: =.03) as well as in estrogen receptor-negative patients (P: =.05). Furthermore, longer treatment reduced contralateral breast cancers and did not increase the number of endometrial cancers. CONCLUSION: Although no survival advantage was noted, patients did benefit from longer tamoxifen treatment over 3 years and had significantly better disease-free survival compared with patients who stopped hormonal treatment. Long-term follow-up is needed to assess these results. Most patients in the long-term group are still receiving treatment. Comparison of results as time passes will enable conclusions to be made on the value of long-term treatment over 5 years compared with 2 to 3 years.

A prospective study of autologous bone marrow or peripheral blood stem cell transplantation after intensive chemotherapy in myelodysplastic syndromes. Groupe Français des Myélodysplasies. Group Ouest-Est d'étude des Leucémies aiguës myéloïdes.

We prospectively assessed autologous stem cell transplantation for consolidation treatment in a trial of intensive chemotherapy in high risk myelodysplastic syndromes (MDS). In this trial, patients aged 55 years or less with no HLA-identical sibling and achieving CR were scheduled to receive unmanipulated autologous bone marrow transplantation (ABMT) preceded by a consolidation chemotherapy course. Forty-two of the 83 patients aged 55 years or less included in the trial (51%) achieved CR. Three were allografted in CR. Twenty-four of the remaining 39 patients who achieved CR (62%) received ABMT (16 patients) or autologous peripheral blood stem cell transplantation (APSCT) (eight patients). Indeed, as bone marrow harvest was often insufficient, APSCT was subsequently proposed after mobilization by consolidation chemotherapy followed by G-CSF. The conditioning regimen combined cyclophosphamide and busulfan. ABMT and APSCT were performed 1-7 months (median 3) after CR achievement. Hematological reconstitution occurred in all patients and tended to be faster after APSCT than ABMT although not significantly. Three patients died from the procedure, nine relapsed after 2-26 months and 12 (50%) were still in CR after 8-55 months. In autografted patients, median Kaplan-Meier disease-free survival and survival were 29 and 33 months from the autograft, respectively. Thus, ABMT or APSCT can be performed in almost two-thirds of MDS patients who achieve CR with intensive chemotherapy. PBSC collection may yield higher numbers of stem cells than marrow collection in some cases, and could improve the percentage of MDS patients autografted in CR. Longer follow-up is required to determine if autograft will prolong CR duration in at least some patients.

Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study.

Mantle cell lymphoma (MCL) is a distinct clinico-pathological entity with a poor prognosis. We have conducted a prospective study in patients with MCL to evaluate a therapeutic strategy in which CHOP polychemotherapy was followed by DHAP if CHOP failed to induce complete remission. Responding patients then proceeded to an intensification therapy with autologous peripheral blood stem cell transplantation (APBSCT). Twenty-eight consecutive patients with newly diagnosed aggressive MCL were included. After four cycles of CHOP regimen, two complete responses (CR) were obtained (7%) and 14 (50%), five (18%) and seven (25%) patients achieved partial (PR), minor (MR) and no response, respectively (one patient died from septic complications during CHOP induction). The two patients in CR after CHOP underwent intensification with TBI, high-dose cyclophosphamide-etoposide and APBSCT. The other twenty-five patients received DHAP and in this group a response rate of 92% (21 CR (84%), two PR (8%)) was observed. Two patients had progressive disease. The twenty-three responding patients received high-dose therapy (TAM8 regimen: TBI-cytarabine-melphalan) followed by APBSCT. One of the two partial responding patients achieved CR after TAM8. After a median follow-up of 47.6 months (range, 14-70), seven patients have relapsed. Our data confirm that: (1) CHOP regimen induces a low CR rate in MCL; (2) CHOP plus DHAP appears to be much more efficient and allows a large proportion of patients to proceed to high-dose therapy in CR; (3) consolidation therapy including TBI and high-dose Arac-C followed by APBSCT may improve event-free survival.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) to increase efficacy of intensive sequential chemotherapy with etoposide, mitoxantrone and cytarabine (EMA) in previously treated acute myeloid leukemia: a multicenter randomized placebo-controlled trial (EMA91 Trial).

The EMA86 study showed efficacy of intensive sequential chemotherapy with mitoxantrone, 12 mg/m2 day on days 1-3, etoposide, 200 mg/m2/day as a continuous infusion on days 8-10 and cytarabine (araC), 500 mg/m2/day as continuous infusion on days 1-3 and 8-10 (EMA regimen) in previously treated patients with AML. The goal of the EMA91 study was to determine whether administration of GM-CSF between the two sequences of EMA chemotherapy and during the second sequence could increase therapeutic efficacy by potentially increasing leukemic cell recruitment into the S phase of cell cycle before the second sequence. One hundred and ninety-two patients aged less than 65 years with previously treated AML received GM-CSF, 5 microg/kg/day or placebo from day 4 to day 8 of EMA chemotherapy. One hundred and twenty were refractory and 72 were in first relapse after a complete remission (CR) of more than 6 months duration. CR rates after one course of chemotherapy were 65% in the GM-CSF group (refractory: 51%; first relapse: 89%), not significantly different from the 59% CR rate (refractory: 46%; first relapse: 81%) in the placebo group. Median time to recovery of neutrophils was 38 and 37 days and median time to last platelet transfusion 32 and 32 days respectively in the GM-CSF and placebo groups. WHO grade > or = 3 non-hematologic toxicities were mainly sepsis (45% and 51%, respectively) and mucositis (34% and 31%) and did not differ between the two groups. Toxic death rate was 5% and 8%, respectively, in the GM-CSF and placebo groups. Patients achieving CR were scheduled to receive six courses of maintenance with reduced-dose EMA. Time to progression tended to be longer in the GM-CSF group (median 154 vs 115 days, progression-free rate at 18 months 33% vs 19%, P = 0.08), particularly in refractory patients (P = 0.06). However, at the current follow-up, this did not translate into a significantly longer disease-free survival and survival. Cell cycle studies showed increased recruitment of cells in the S phase between day 4 and day 8 in the GM-CSF group compared to placebo (P = 0.006). However, this did not significantly relate to prognosis in this cohort of patients. GM-CSF might marginally increase efficacy of sequential chemotherapy without increasing its toxicity in the absence of any detected relationship between this effect and observed leukemic cell recruitment into the cell cycle.

Autologous hematopoietic stem cell transplantation in elderly patients (≥ 70 years) with non-Hodgkin's lymphoma: A French Society of Bone Marrow Transplantation and Cellular Therapy retrospective study.

INTRODUCTION: Limited data is available on the feasibility of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) in elderly patients over 70 years of age with non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: In the setting of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) group, we retrospectively analyzed 81 consecutive patients with NHL over 70 years of age who received AHSCT. RESULTS: The median age at AHSCT was 72.3 years [70-80]. Patients' were diagnosed with diffuse large B-cell lymphoma (n=40), follicular lymphoma (n=16), mantle cell lymphoma (n=15), T-cell lymphoma (n=5), and other (n=5). Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) was 0 in 73% of patients. Main conditionings were BEAM (Carmustine-Etoposide-Cytarabine-Melphalan, n=61) and melphalan alone (n=14). Median delays to reach 0.5×109/L neutrophils and 20 × 10(9)/L platelets were of 12 [9-76] days and 12 [0-143] days, respectively. One hundred day and one year cumulative incidence of NRM was 5.4% and 8.5%, respectively. The main cause of death remains relapse. CONCLUSION: In conclusion, this study revealed that AHSCT seemed to be acceptable in patients over 70 years of age with NHL. Patient age is not a limiting factor if clinical condition is adequate.

Purification and properties of methanol dehydrogenase from Methylophaga marina.

Purification of methanol dehydrogenase from Methylophaga marina, in order to avoid the instability observed in crude extracts, was achieved initially by a rapid procedure using mainly an aqueous two-phase partition system composed of polyethylene glycol 1000 (50%, v/v) and potassium phosphate (50%, w/v). The purified enzyme gave a single band of protein after SDS-polyacrylamide gel electrophoresis. Antiserum raised against purified methanol dehydrogenase was used to detect possible protein contaminants in the enzyme preparation. The enzyme is an NAD-independent dehydrogenase containing pyrrolquinoline quinone (PQQ) as a prosthetic group. It is made of two apparently identical subunits giving a total MW of 145,000 for the native enzyme. The isoelectric point is 6.4. In addition to methanol and formaldehyde, multicarbon primary alcohols and aldehydes as well as secondary alcohols can be used as substrates. Except for ammonium chloride, which is a necessary activator in vitro, no effector was found which could modify the rate of enzyme activity under standard conditions of the assay. Although the main properties of this methanol dehydrogenase are similar to those already described in the literature, it does not belong in any of the five categories described by Anthony.

The genus Methylophaga, a new line of descent within phylogenetic branch gamma of Proteobacteria.

The genus Methylophaga with two species, M. marina and M. thalassica, comprises halophilic methylotrophic bacteria. These organisms utilise C1 compounds through the ribulose monophosphate pathway and are unable to grow on methane. Nearly complete 16S rRNA sequences were obtained for both Methylophaga species by directly sequencing the amplified 16S rRNA gene. These sequences were compared with published 16S rRNA sequences of methylotrophic strains and a large number of marine bacterial strains including several members of the alpha, beta and gamma subclasses of Proteobacteria. Phylogenetic trees were inferred using both parsimony and distance matrix methods. Each topology was analysed by bootstrap. The genus Methylophaga was found to be clearly separated from other methylotrophic bacteria and formed a distinct branch within the gamma subclass of Proteobacteria.

Successful cryopreservation of purified autologous CD34+ cells: influence of freezing parameters on cell recovery and engraftment.

Conventional hematopoietic stem cell cryopreservation methods use a DMSO concentration of 10%. However, cells manipulated ex vivo may require more refined freezing protocols adapted to the specific cell suspension. In this retrospective study, we evaluated the results obtained with CD34+ cells purified from peripheral blood of 39 patients on the CEPRATE SC System and frozen in 7.5% DMSO with a view to transplantation. The post-freezing recovery of progenitor cells was 89.4 +/- 27.87% for CD34+ cells, 59.13 +/- 36.93% for CFU-GM, and 53.49 +/- 40.71 for BFU-E. Neither the purity of the suspension nor the nucleated cell density during freezing was predictive of cell recovery. No difference was observed between cells stored in vials and bags. Thirty-seven patients transplanted with the concentrated CD34+ fraction received 4.46 x 10(6) CD34+ cells/kg and 33.04 x 10(4) CFU-GM/kg. The median time to granulocyte (>0.5 x 10(9)/l) and platelet (>50 x 10(9)/l) engraftment was 11 and 13 days, respectively. Only cell density and the infused number of CD34+ cells and CFU-GM were significantly related to hematological recovery. Our data suggest that purified CD34+ cells can be successfully cryopreserved in 7.5% DMSO and may represent a first step in establishing freezing parameters for selected CD34+ cells.

Cyclophosphamide/mitoxantrone/melphalan (CMA) regimen prior to autologous bone marrow transplantation (ABMT) in metastatic breast cancer.

Dose-intensive treatment followed by ABMT is currently used in different approaches to treat breast cancer patients. An active non cross-resistant regimen combining cyclophosphamide (C), mitoxantrone (M) and melphalan (A) (CMA), was developed as the conditioning regimen before ABMT. The purpose of this phase II study was to evaluate this protocol and the duration of its effect in metastatic patients, who responded to chemotherapy. Criteria for inclusion included histologically documented breast cancer, age < 55 years and the first detection of measurable metastatic lesions. Following first-line chemotherapy in responding patients, histologically negative bone marrow was collected and cryopreserved. Then, intensification with cyclophosphamide (120 mg/kg), mitoxantrone (60 mg/m2), and melphalan (140 mg/m2) was followed by ABMT. Sixty-one metastatic breast cancer patients with a mean age of 40 years were included. Sites of measurable metastases included: liver 24, lung 14, central nervous system four, pleura three, skin six, and chest wall six, nodes eight and bone marrow one. Nineteen patients had lesions in two or more sites, and 22 had bone involvement. The response of 60 patients could be evaluated: before ABMT 31 were in clinical complete response (CR), 22 in partial response > 50% (PR), and seven had new progression. After ABMT, 36 patients were in CR, 16 in PR, one progressed and one was stable. Seven (11.5%) toxic deaths occurred. Mean time for hematological recovery was 32.5 days, without hematopoietic growth factors. Median survival was 33 +/- 9.4 months from the start of therapy, and 25.7 +/- 4.6 months from the date of ABMT. Median event-free survival was 20 months from the start of therapy, and 13 +/- 2 months from ABMT. With a median follow-up of 51 months, probability of actuarial survival, measured from the beginning of initial chemotherapy, was 36%, and event-free survival was 18%. In metastatic breast cancer responding to chemotherapy, high-dose consolidation with CMA and ABMT resulted in a median survival of 33 months. These results lay the ground work for evaluation in a randomized trial in metastatic breast cancer.

Quinine improves results of intensive chemotherapy (IC) in myelodysplastic syndromes (MDS) expressing P-glycoprotein (PGP). Updated results of a randomized study. Groupe Français des Myélodysplasies (GFM) and Groupe GOELAMS.

We designed a randomized trial of IC with or without quinine, an agent capable of reverting the multidrug resistance (mdr) phenotype, in patients aged < or = 65 years with high risk MDS. Patients were randomized to receive Mitoxantrone 12 mg/m2/d d2-5 + AraC 1 g/m2/12 h d1-5, with (Q+) or without (Q-) quinine (30 mg/kg/day). 131 patients were included. PGP expression analysis was successfully made in 91 patients and 42 patients (46%) had positive PGP expression. In PGP positive cases, 13 of the 25 (52%) patients who received quinine achieved CR, as compared to 3 of the 17 (18%) patients treated with chemotherapy alone (p = 0.02). In PGP negative cases, the CR rate was 35% and 49%, respectively in patients who received quinine or chemotherapy alone (difference not significant). In the 42 PGP positive patients, median Kaplan-Meier (KM) survival was 13 months in patients allocated to the quinine group, and 8 months in patients treated with chemotherapy alone (p = 0.01). In PGP negative patients, median KM survival was 14 months in patients allocated to the quinine group, and 14 months in patients treated with chemotherapy alone. Side effects of quinine mainly included vertigo and tinnitus that generally disappeared with dose reduction. Mucositis was significantly more frequently observed in the quinine group. No life threatening cardiac toxicity was observed. In conclusion, results of this randomized study show that quinine increases the CR rate and survival in PGP positive MDS cases treated with IC. The fact that quinine had no effect on the response rate and survival of PGP negative MDS suggests a specific effect on PGP mediated drug resistance rather than, for instance, a simple effect on the metabolism of Mitoxantrone and/or AraC.

[Mitomycin-vinorelbine combination as second-line chemotherapy in metastatic cancer of the breast]. / Association mitomycine-vinorelbine en deuxième ligne chimiothérapique dans le cancer du sein métastatique.

Fourty-six patients (41 evaluable) were treated in second line chemotherapy of metastatic breast cancer (MBC) by an association of mitomycin (M), vinorelbine (V) (M 8 mg/m2 D1, V 25 mg/m2 D1 and DI 8 every 4 weeks). Median age was 58 years (36-78), median performance status 1 (0-3). Thirty-seven per cent of the tumors were estrogen receptors positive and 17% progesterone receptors positive. Seventeen patients received an adjuvant chemotherapy and 39 a first line chemotherapy with anthracycline (A). The median number of metastatic sites was 2 (1-4) and 27 patients (67%) had visceral metastases. Twelve patients were refractory to anthracyclines and 5 resistant. No toxic death nor hemolytic uremic syndrome were observed. Seven (3.7%) febrile neutropenias happened responsible for 4 hospitalizations. A grade 3 or 4 neutropenia was noted in 34% of the cycles but no other clinic toxicity nor grade 3 or 4 thrombopenia. The rate of objective response (OR) was 37.5% with 2 complete responses (CR) and 13 partial responses (PR). Seven patients had stable disease and 18 progressed. The rate of hepatic OR was 31%. Five (40%) A-refractory patients responded but no resistant patient. Median OR time was 10 weeks (8-12) and median OR duration was 5 months (3-6). Median survival was 11.5 months. MV association is well tolerated and effective in second line chemotherapy for MBC even with hepatic metastasis and in patients refractory to anthracyclines.

[Tamoxifen adjuvant delays early breast cancer. Results of a cooperative randomized trial]. / Tamoxifène adjuvant retardé dans le cancer du sein curable. Résultats d'un essai coopératif randomisé.

Adjuvant tamoxifen (TAM) has been proved to reduce recurrence and mortality in early breast cancer, nevertheless many patients did not receive TAM as adjuvant therapy after local treatment. In order to study the efficacy of delayed TAM therapy in patients who were not given immediate adjuvant hormonal treatment, a multicenter randomized trial has been conducted by the French National Cancer Centers (FNCLCC). According to eligibility criterias all women with breast cancer who received curative local treatment at least 2 years before (surgery +/- radiotherapy) with or without adjuvant chemotherapy but no hormonal treatment could have been included. Between September 1986 and October 1989, 494 women were randomized to receive either TAM 30 mg/day for 5 years or no treatment. Patients' characteristics such as age, tumoral stage, number of positive nodes, receptors status and time from local treatment were equally distributed in the 2 groups. An improvement in the disease free survival in the TAM treated patients can be observed with a significative difference (p = 0.05), nevertheless the overall survival is not improved in the TAM group. In the same way, in nodes positive patients although no significative improvement in the overall survival can be observed, a significative improvement in the disease free survival (p = 0.05) can be noted. In estradiol receptors positive patients tamoxifen gives a significative reduction in the odds of death (p = 0.04) and recurrence (p = 0.03). The disease free improvement seems to be limited to 50 and more years old patients. The first results of this trial lead to prescribe tamoxifen to all postmenopausal women previously treated for an early breast cancer without adjuvant tamoxifen treatment.

[In utero transfer for preterm labor: experience of a regional perinatal hotline providing a 24-hour on call service]. / Evaluation de l'algorithme de prise en charge des appels pour menace d'accouchement prématuré utilisé par la cellule de transfert périnatal de la région Rhône-Alpes.

OBJECTIVE: Preterm labor is one of the major causes of concern for level I and II obstetricians. The purpose of this study was to determine the incidence of in utero transfer performed for preterm labor. We also aimed to evaluate the algorithm we used in case of call for preterm labor. This algorithm allowed us to study the rate of endovaginal sonography use prior to in utero transfer, to calculate its predictive value and to evaluate the risk of delivery during transfer. PATIENTS AND METHOD: We conducted an 8-months prospective study of all calls for preterm labor received at a regional call center in France (EU). All obstetrical data were entered in a computerized anonymous database. Three months after the first call midwives collected data from the receiving hospital. RESULTS: Calls for preterm labor account for 40% of calls for in utero transfer. Two hundred and sixty-five calls have been received for preterm labor; among them 50 cases were associated with a preterm rupture of membrane, a maternal or fetal pathology and 14 cases were lost for follow-up. Those 64 cases were excluded leaving 201 cases for analysis. Twenty-eight had a cervix dilated 4 cm, or more, while 173 had a cervix dilated less than 4 cm. Fifty percent of woman that had a cervical dilatation of 4 cm or more delivered more than 4 h after the call. Among the 173 patients that had a cervix dilated less than 4 cm, 71% had not delivered 7 days after the hotline call and 26% had an endovaginal ultrasonography performed before the transfer. None of the women that had a cervical length longer than 27 mm delivered in the 7 following days. None of the 176 women that were transferred delivered during the transfer. DISCUSSION AND CONCLUSION: In utero transfer for preterm labor is the leading cause of in utero transfer. Endovaginal ultrasonography prior to transfer should be performed in order to avoid unnecessary transfer. Women who have a preterm labor with a cervical dilatation of 4 cm or more are not an absolute contra-indication to in utero transfer. In those cases the transfer indication should be discussed on a case-to-case basis including the actual term and the distance between hospitals.

[Vancomycin in meningitis caused by penicillin G resistant Streptococcus pneumoniae]. / Vancomycine dans les méningites à Streptococcus pneumoniae résistant à la pénicilline G.

We report two cases of penicillin G-resistant pneumococcal meningitis in adults, with clinical and bacteriological failure of amoxicillin and negative or incomplete response to third generation cephalosporins. Meningitis occurred in a man treated for myeloma and in an elderly woman under prolonged intermittent amoxicillin therapy for chronic otitis. Such situations are known as exposing to pneumococcal meningitis and to resistance of the strain involved to penicillin G. Both patients were cured by vancomycin in continuous infusion associated with rifampicin or fosfomycin. Contrary to third generation cephalosporins, which have higher minimal inhibitory concentrations, vancomycin and rifampicin are still fully active against penicillin G-resistant pneumococcal strains. Thus, vancomycin administered in continuous infusion and associated with rifampicin and fosfomycin deserves to be tried as first-line treatment of pneumococcal meningitis in patients at risk of resistance to penicillin G.

[Leukemia and pre-leukemic conditions occurring after treatment of breast cancer]. / Leucémies et états préleucémiques survenus après traitement d'un cancer du sein.

OBJECTIVE: The purpose of this study was to determine the clinical and prognostic features of leukemias and preleukemic states, whatever the mode of development, observed in patients after treatment of breast cancer. PATIENTS AND METHODS: A retrospective multicentric analysis was made of 121 patients treated for breast cancer and who later developed leukemia or a preleukemic state. Initially, 44 patients had undergone mastectomy, 72 had conservative surgery and 119 had locoregional irradiation. At least one chemotherapy session was performed in 90 patients and 48 had received tamoxifen. The risk of relapse of breast cancer was high, moderate or low for 44, 46 and 24 patients respectively (data not available for 7 patients). RESULTS: By class, the hematology diseases found were: myelodysplasia (n = 9), refractory anemia with blast excess (n = 7), acute lymphoblastic leukemia (n = 6), acute myoblastic leukemia (n = 93 including a majority of type 2 and type 4). For acute myeloblastic leukemia, mean delay to onset was 65 and 37 months respectively without and after chemotherapy. The prognosis of these cases of leukemia and preleukemic states was poor with an overall death rate of 86%. CONCLUSION: In light of the recent development of indications for adjuvant chemotherapy even for subgroups of patients at moderate risk, it is important to more precisely assess the absolute benefit in terms of survival compared with the risk of severe complications, particular secondary leukemia. In the future, a systematic registry and a case-control study are required.