Agricultural exposures and DNA damage in PBMC of female farmers measured using the alkaline comet assay.

OBJECTIVE: Several studies investigated the link between agricultural occupational exposures and DNA damage, in an attempt to bring elements of biological plausibility to the increased cancer risk associated with them. However, only a few of these studies focused on females. METHODS: The comet assay was performed on PBMC (Peripheral Blood Mononuclear Cells) samples from 245 females working in open field farming and cattle raising, located in the Normandy area of France. Individual questionnaires on tasks performed were administered at the time of sampling to directly assess exposures. Environmental exposures were issued from a questionnaire assessing the farm productions. Linear regression analyses were done using the DNA damage scores. RESULTS: Regarding direct exposures, several tasks associated with exposure to potentially harmful chemicals were not associated with DNA damage, but a longer duration of use of herbicide on meadows (p = 0.05) or of cleaning and upkeep of agricultural equipment (p = 0.06) revealed higher DNA damage levels, although the number of exposed women was low. Several indirect and/or environmental exposures were associated with DNA damage in multivariate analyses: a larger surface of meadows (p = 0.006) or the presence of poultry (p = 0.03) was associated with less DNA damage, while the presence of swine (p = 0.01) was associated with higher DNA damage. Smokers and former smokers had less DNA damage than non-smokers (p = 0.0008 and p = 0.03). CONCLUSIONS: We report modified levels of DNA damage for those environmentally exposed to meadows, poultry and pig farming, underlining the need for a better knowledge of the potential health risks experienced by females in this setting.

Effect of single-unit transfusion in patients treated for haematological disease including acute leukemia: A multicenter randomized controlled clinical trial.

BACKGROUND: Retrospective studies in hematological unit have suggested that single red blood cell (1-RBC) unit transfusion policy may reduce the number of RBC used without negative clinical impact. METHOD: Acute leukemia patients requiring intensive chemotherapy or patients receiving autologous or allogeneic transplantation were randomly assigned to receive either single RBC (1-RBC arm) or double RBC (2-RBC arm) per transfusion with a hemoglobin trigger of 8 g/dL. The primary composite endpoint was the percentage of patients experiencing serious complications, such as a non-hematological adverse event grade ≥ 3 or intensive care admission or death. FINDINGS: A total of 981 and 592 RBC transfusions were required in the 1-RBC arm (n = 125) and the 2-RBC arm (n = 120), respectively. The mean pre-transfusion hemoglobin levels were 7.49 ± 0.83 g/dL in the 1-RBC arm and 7.46 ± 0.67 g/dL in the 2-RBC arm (p = 0.275). The predefined non-inferiority criteria was achieved with 28/125 patients reaching the primary endpoint in the 1-RBC arm (22.4 %) and 28/120 patients in the 2-RBC arm (23.3 %) (Risk difference 0.009; 95 %, Confidence interval [-0.0791 to 0.0978], p = 0.021). The median (IQR) of RBC units transfused per patient was 7 (4-12) in the 1-RBC arm and 8 (4-12) in 2-RBC arm. Hemoglobin levels at discharge were also comparable in both arms. INTERPRETATION: The results of this trial indicate that a single RBC transfusion policy is not inferior to a double RBC transfusion policy for patients receiving a bone marrow transplant or intensive chemotherapy in a hematological intensive care unit. However, the single RBC transfusion policy did not reduce the number of RBC units transfused per stay. FUNDING: This trial was funded by a grant from the French Ministry of Health.

Low dose Rituximab for pre-emptive treatment of Epstein Barr virus reactivation after allogenic hematopoietic stem cell transplantation.

INTRODUCTION: The most used preemptive therapy for Epstein Barr virus reactivation post allogeneic hematopoietic stem cell (HSCT) transplant is Rituximab, 375 mg/m2, once weekly until EBV viremia negativity. There is no data suggesting such a high dose. OBJECTIVE: We hypothesized that a lower dose of Rituximab would be as efficient with less toxicity. PATIENTS: In a retrospective, monocentric study, we analyzed 16 consecutive patients treated preemptively with low dose Rituximab for EBV reactivation post HSCT. Patients were treated with low Rituximab dose of 100 mg/m² weekly. Success was defined by a decrease of EBV viremia of 1 log10 and below 1000 UI/ml, and the absence of post-transplant lymphoproliferative disorder (PTLD). RESULTS: Success rate was 93.4% (15/16). One (1/16, 6%) PTLD was diagnosed after preemptive therapy, despite a negative viremia. CONCLUSION: A low dose of Rituximab of 100 mg/m² per injection for pre-emptive therapy of EBV reactivation post HSCT is safe and effective for preventing PTLD. Prospective, randomized, multicentric trials with larger number of patient are needed to determine the best rituximab dose.

Reduced-intensity and non-myeloablative allogeneic stem cell transplantation from alternative HLA-mismatched donors for Hodgkin lymphoma: a study by the French Society of Bone Marrow Transplantation and Cellular Therapy.

Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N=34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N=31, 91%) or a RIC (N=3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR)=2.02, P=0.03 and HR=2.43, P=0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with post-transplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting.

Rituximab salvage therapy in adults with immune thrombocytopenia: retrospective study on efficacy and safety profiles.

Splenectomy remains the preferred treatment for chronic immune thrombocytopenia (ITP) after corticosteroid failure, despite the risks of despite surgical complications and infection. The aim of this study was to assess the efficacy of and tolerance to rituximab through a retrospective analysis of 35 refractory/relapsing ITP patients treated from 2004 to 2013. The median age of subjects was 46 years (14-80). Rituximab was given at a weekly dose of 375 mg/m(2) for 4 weeks. Median time from diagnosis to first infusion was 17 months (1-362) and follow-up was 47 months (2-133). The overall response rates at 1 and 2 years after the first infusion were 47 and 38 %, with complete response rates of 24 and 25 %, respectively. Median duration of response was 38 months (1-123), with 37 % of patients maintaining a durable response (>1 year). Twenty-nine percent of patients had undergone splenectomy. A durable response after rituximab was more frequently observed in patients undergoing second-line therapy than those in third or later (83 versus 35 %, P = 0.01). Forty-four percent of patients experienced mild hypogammaglobulinaemia after rituximab, and no clinical infection occurred. To conclude, rituximab should be considered as an alternative treatment to splenectomy. Its efficacy and safety profile should lead us to choose this medical option therapy before surgery for ITP patients.

Nature and decomposition degree of cover crops influence pesticide sorption: quantification and modelling.

This study quantifies and models the influence of the type and the degree of decomposition of cover crops (CC) on three pesticides sorption: epoxiconazole (EPX), S-metolachlor (SMOC) and glyphosate (GLY). Residues of four cover crop species were incubated for 0, 6, 28 or 56 d in controlled conditions. For each incubation time, adsorption of pesticides on CC residues was measured in batch experiments. Additionally, the biochemical and elemental composition (Van Soest fractionation, C:N, (13)C NMR spectroscopy) of CC was characterized. Mineralization of CC residues was monitored at all incubation times using CO2 trapping. Results showed that the adsorption of pesticides differed significantly according to (i) the type of molecule, (ii) the type of CC, (iii) the degree of CC decomposition and the interaction CC×decomposition time. EPX and GLY were the most (Kd ranging from 188 to 267 L kg(-1)) and the least (Kd ranging from 18 to 28 L kg(-1)) sorbed pesticides respectively. With increasing decomposition of the CC residue, sorption increased by 1.6- to 4.7-fold according to the type of pesticide and cover crop. It was significantly correlated with the net cumulative mineralization (ρ>0.7) and other indicators of biochemical composition such as C:N ratio (ρ<-0.7), the Van Soest neutral detergent soluble fraction (ρ>0.5) and the alkyl/O-alkyl C ratio determined by NMR. An innovative model based on net cumulative mineralization of CC residues is proposed to describe the pesticide sorption and appears to be a promising approach to account for the effects of decaying plant residues on the environmental fate of pesticides.

Adrenal rest tumor of the liver causing Cushing's syndrome: treatment with ketoconazole preceding an apparent surgical cure.

Ketoconazole, an imidazole derivative known to inhibit cytochrome P450-dependent adrenal enzymes was given to a patient with a functioning adrenal rest tumor of the liver in preparation for surgery. The drug was administered in a stepwise manner for 42 days starting with 400 mg and reaching 1 g the last 4 weeks of the trial. Clear clinical improvement was evident early in the trial and was associated with evidence of amelioration of her hypercortisolism and striking changes in serum and urinary levels of steroid hormones and metabolites. Sex steroids in serum and urine fell dramatically from the first day to the end of the trial. Urinary 17-ketosteroid excretion fell from a basal average of 139 mg/24 h to near normal levels within a week of therapy; serum testosterone fell from a basal level of 2.4 to 0.18 ng/ml; serum 17 beta-estradiol fell likewise from 1096 to 150 pg/ml. In contrast, cortisol levels in serum and urine increased in the first 2 weeks of the trial and subsequently fell to values below the basal levels. Similarly, serum 17 alpha-OH-progesterone levels increased 63% above the basal levels by day 6 of the trial and declined afterwards. Nine months after successful tumor resection the patient is apparently cured as judged by steroid hormone levels and physical appearance. We conclude that ketoconazole was effective in blocking tumoral steroidogenesis which resulted in clinical benefit.

[Technical problems associated with the cold chain]. / Problèmes techniques liés à la chaîne du froid.

After having covered the current status of the cold chain in France, the author highlights the economic impact of refrigerated storage and processing involving refrigeration. Lose reduction is such that the return on investments is estimated as being roughly 3 years. In years to come, progress will be achieved in the field of plant design. Some information on design trends is provided. Operators in general, and carriers in particular, are faced with an increasingly complex regulatory framework leading to a competition imbalance. The current cold chain developmental trend is characterized by complex computer management of logistics: the flow of goods is modulated in order to meet the production to the distribution needs as cost effectively as possible. This logistic strategy enables management of downstream to upstream interfaces involving various operators. Finally, the author indicates the main causes of non-compliance with the cold chain, generally at retail and consumer levels.

[Cold chain --the concept of traceability-- practical applications]. / Chaîne du froid--concept de traçabilité--applications pratiques.

Traceability makes it possible to monitor the properties of a foodstuff in general and its safety in particular. Based on the "refrigerated trio" concept developed by André Monvoisin, cold chain implementation conditions are examinated, with emphasis on the following three aspects, a safe product and early and continuous application of refrigeration. The TTT and PPP theories are presented. Following an overview of the French Academy of Medicine and the National Consumer Centre's recommendations, non compliance with the cold chain at household refrigerator level is discussed along with control equipment for refrigerators and products. Various indicators and integrators are presented and their described. Time-temperature integrators are examined in depth. In the conclusion, the authors stress the need to restore consumer confidence following recent foof-safety scares.

Feasibility of the fludarabine busulfan 3 days and ATG 2 days reduced toxicity conditioning in 51 allogeneic hematopoietic stem cell transplantation: a single-center experience.

In reduced-toxicity conditioning hematopoietic stem cell transplantation, several studies failed to demonstrate the superiority of one conditioning over another. This study described 51 patients (median age of 58 years) allografted with the new FB3-ATG2 conditioning regimen for myeloid (66%) or lymphoid disease (33%). Comorbidity index ≥3 was noted in 23.5% of patients. Toxicities were close to those observed with RIC. One-year cumulative incidence of acute and chronic GVHD was 18.9% and 39.2%. The 2-year-NRM, DFS and OS were 25%, 57.5% and 66%. The FB3-ATG2 regimen is safe and efficient in both lymphoid and myeloid disorders. However, prospective comparative studies are needed.

Predictive factors for a single successful cytapheresis session during the first mobilisation.

To avoid repeated apheresis, the objective of this study was to analyse the predictive factors for a single successful cytapheresis during the first mobilisation. The pre-collection characteristics of 170 lymphoma and 95 myeloma patients were analysed. Among 60 lymphoma patients who had less than 30 CD34 cells/mm(3) the day before the first apheresis, an increase in the CD34 cell count between Day -1 and Day 1 was predictive of first stem cell mobilisation success, with a sensitivity of 100% if the Day 1 was higher than 30/mm(3) (10/60 patients). Success rate of obtaining an appropriate number of stem cells in one apheresis was 120 among 170 patients.

New development on materials and techniques used in the heraldic designs of illuminated Manueline foral charters by multi-analytical methods.

In the illuminated foral charters commissioned by D. Manuel I, King of Portugal (1495-1521), heraldry played a prominent role. In this work, royal emblems corresponding to the third heraldic design, applied to the Charter of Couto de Teixedo, are studied by means of EDXRF, SEM-EDS, micro-Raman, micro-FTIR and HPLC-DAD to characterize the materials and techniques used to produce this masterpiece of Portuguese Renaissance. By comparing this data with the results previously obtained in other three charters, this research allows for the first time an accurate insight into the reformed manuscripts production, especially since the illuminated charters under consideration were all investigated on the basis of similar micro-spectroscopic techniques. Inks, metal coatings, pigments, organic dyes, fillers or extenders, and binding media are discussed, and their use enlightened by the politic and legal messages the foral charters had to convey. Parchment analysis allowed us to identify the animal species, and all undertaken processes along its preparation. HPLC-DAD allowed us to differentiate the gums used. CaSO4 was observed in the parchment as a degradation product of CaCO3 used in parchment production in the presence of metal sulfates coming from the ink. Pigments used in the different colors as well as some specific phases for some colors were identified. Silvering and gilding processes, metal caratage and silver oxidation compounds were also objects of the present study.

Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE-/-) and wild-type (APOE+/+) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE-/--challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge.

[Evolution of antibiotic resistance and serogroups of Streptococcus pneumoniae over the 1997-2003 period in Brittany]. / Evolution de la résistance aux antibiotiques et des sérogroupes de Streptococcus pneumoniae en Bretagne entre 1997 et 2003.

At this time, many antibiotics have decreased activity against Streptococcus pneumoniae, a major agent of infectious disease. In this study, we evaluated antibiotic susceptibility and serogroups of strains isolated from bacteraemia, meningitis and acute otitis media in adults and children over the 1997-2003 period in Brittany, France. In 2003, 62% of the isolates were not susceptible to penicillin and 11% were fully resistant. The prevalence of erythromycin resistance was 63%. Resistance rates were higher among isolates recovered from children than adults. Serogroups 19 and 14 were the most frequently isolated, especially the 19 one among children. The emergence of this serogroup might be a consequence of the use of heptavalent conjugate vaccine introduced in 2001 in France. Future surveillance after vaccination will be needed to detect emerging serogroups and resistance among S. pneumoniae.

[Primary hyperparathyroidism caused by a mediastinal adenoma with intermittent hypercalcemia and severe bone disease]. / Hiperparatiroidismo primario por adenoma mediastínico, con hipercalcemia intermitente y enfermedad ósea acentuada.

We report the case of a 33-year-old woman who was operated on with the diagnosis of primary hyperparathyroidism (PHP) in 1986. She had bone disease and slight hypercalcemia. Two parathyroid glands were removed with a lack of clinical improvement. Subsequently, the serum calcium levels were normal with occasional slight increases. Depressed phosphorus values and elevated alkaline phosphatases and PTH levels were also present, associated with severe bone involvement and muscular weakness. A second cervical exploration performed in 1989 disclosed only a normal parathyroid gland, which was not removed. In 1990, a thoracic CT scan showed the presence of a 1 cm mediastinal nodule close to the great vessels. A thoracotomy was performed to remove this nodule, which proved to be a parathyroid adenoma. After surgery, the patient presented with a "hungry bone" syndrome, characterized by very low levels of calcium, phosphorus and magnesium, which required enteral and parenteral calcium and magnesium supplements, plus dihydroxyvitamin D. The association of normocalcemia and intermittent hypercalcemia with severe bone disease is very rare, as is the presence of a mediastinal adenoma. This could explain the difficulty in the diagnosis in this case.

[Thyroid nodule in Basedow-Graves disease and thyroid cancer: experience in 6 patients]. / Nódulo tiroideo en enfermedad de Basedow Graves y cáncer tiroideo: experiencia en 6 pacientes.

Traditionally, Basedow-Graves disease was considered a protection against thyroid cancer. However, recent reports suggest that cancer occurs with a higher frequency than expected and is more aggressive in this disease. We report six patients with hyperthyroidism due to a Basedow Graves disease that presented a palpable thyroid nodule, which was cold in the scintiscan and solid in the ultrasound examination. Fine needle cytology disclosed cancer in five cases (two with cytological features of greater aggressiveness) and a nodular hyperplasia in one. The diagnosis was confirmed in the surgical piece in all patients. We conclude that Basedow-Graves disease and thyroid cancer, which can have an increased aggressiveness, may coexist.