Genome analysis of Lachnoclostridium phocaeense isolated from a patient after kidney transplantation in Marseille.

Lachnoclostridium phocaeense is a new species in the genus Lachnoclostridium. Lachnoclostridium phocaeense is a Gram-positive anaerobic rod. This strain, Marseille-P3177T (CSUR = P3177) with the below described genome was isolated from the urine sample of a women after kidney transplantation. The strain genome is 3 500 754 bp long with 50.62% G + C content and consists of a single contig (GenBank accession number NZ_LT635479.1).

Varibaculum massiliense sp. nov., a new bacterium isolated from human urine with culturomics.

Varibaculum massiliense sp. nov. strain Marseille-P2802T (= CSUR P2802 = DSM 103074) is a new species within the genus Varibaculum in the phylum Actinobacteria that was isolated from the urine of a 59-year-old man treated with chronic haemodialysis for diabetic nephropathy.

Alloy and composition dependence of hydrogen embrittlement susceptibility in high-strength steel fasteners.

High-strength steel fasteners characterized by tensile strengths above 1100 MPa are often used in critical applications where a failure can have catastrophic consequences. Preventing hydrogen embrittlement (HE) failure is a fundamental concern implicating the entire fastener supply chain. Research is typically conducted under idealized conditions that cannot be translated into know-how prescribed in fastener industry standards and practices. Additionally, inconsistencies and even contradictions in fastener industry standards have led to much confusion and many preventable or misdiagnosed fastener failures. HE susceptibility is a function of the material condition, which is comprehensively described by the metallurgical and mechanical properties. Material strength has a first-order effect on HE susceptibility, which increases significantly above 1200 MPa and is characterized by a ductile--brittle transition. For a given concentration of hydrogen and at equal strength, the critical strength above which the ductile-brittle transition begins can vary due to second-order effects of chemistry, tempering temperature and sub-microstructure. Additionally, non-homogeneity of the metallurgical structure resulting from poorly controlled heat treatment, impurities and non-metallic inclusions can increase HE susceptibility of steel in ways that are measurable but unpredictable. Below 1200 MPa, non-conforming quality is often the root cause of real-life failures.This article is part of the themed issue 'The challenges of hydrogen and metals'.

'Ndongobacter massiliensis' gen. nov., sp. nov., a new bacterial genus isolated from a human urine sample after de novo kidney transplantation.

We report the main characteristics of 'Ndongobacter massiliensis' strain Marseille-P3170T (= CSUR P3170), which was isolated from the urine sample of a 37-year-old man who had just received a kidney transplant for genetic focal segmental glomerulosclerosis.

'Lachnoclostridium urinimassiliense' sp. nov. and 'Lachnoclostridium phocaeense' sp. nov., two new bacterial species isolated from human urine after kidney transplantation.

We describe here the main features of 'Lachnoclostridium urinimassiliense' strain Marseille-P2804T (= CSUR P2804) and 'Lachnoclostridium phocaeense' strain Marseille-P3177T (= CSUR P3177) that were isolated from urine samples after kidney transplantation in two women.

'Actinotignum timonense' sp. nov., a new bacterial species isolated from a human urine sample.

We report here the main characteristics of 'Actinotignum timonense' strain Marseille-P2803T (= CSUR P2803) that was isolated from the urine sample of a 59-year-old man with end-stage renal disease.

'Peptoniphilus urinimassiliensis' sp. nov., a new bacterial species isolated from a human urine sample after de novo kidney transplantation.

We describe here the main features of 'Peptoniphilus urinimassiliensis' strain Marseille-P3195T (= CSUR P3195) that was isolated from the urine sample of a 37-year-old man who had just received a kidney transplant for genetic focal segmental glomerulosclerosis.

"Varibaculum massiliense" sp. nov., a new bacterial species isolated from human urine.

We report the main characteristics of "Varibaculum massiliense" strain Marseille-P2802(T) (=CSUR P2802), which was isolated from urine sample of a 59-year-old man with end-stage renal disease.

Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs.

Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma. Most of the data available on GISTs derive from retrospective studies of patients referred to oncology centers. The MolecGIST study sought to determine and correlate clinicopathological and molecular characteristics of GISTs. Tumor samples and clinical records were prospectively obtained and reviewed for patients diagnosed in France during a 24-month period. Five hundred and ninety-six patients were included, of whom 10% had synchronous metastases. GISTs originated from the stomach, small bowel or other site in 56.4, 30.2 and 13.4% of cases, respectively. The main prognostic markers, tumor localization, size and mitotic index were not independent variables (P < 0.0001). Mutational status was determined in 492 (83%) patients, and 138 different mutations were identified. KIT and PDGFRA mutations were detected in 348 (71%) and 74 (15%) patients, respectively, contrasting with 82.8 and 2.1% in patients with advanced GIST (MetaGIST) (P < 0.0001). Further comparison of localized GISTs in the MolecGIST cohort with advanced GISTs from previous clinical trials showed that the mutations of PDGFRA exon18 (D842V and others) as well as KIT exon11 substitutions (W557R and V559D) were more likely to be seen in patients with localized GISTs (odds ratio 7.9, 3.1, 2.7 and 2.5, respectively), while KIT exon 9 502_503dup and KIT exon 11 557_559del were more frequent in metastatic GISTs (odds ratio of 0.3 and 0.5, respectively). These data suggest that KIT and PDGFRA mutations and standardized mitotic count deserve to be investigated to evaluate the relapse risk of GISTs.

Prognosis and predictive value of KIT exon 11 deletion in GISTs.

BACKGROUND: KIT exon 11 mutations are observed in 60% of gastrointestinal stromal tumours (GIST). Exon 11 codes for residues Tyr568 and Tyr570, which play a major role in signal transduction and degradation of KIT. Our aim was to compare the outcome of patients with deletion of both Tyr568-570 (delTyr) and the most frequent deletion delWK557-558 (delWK). METHODS: Pathology and clinical characteristics of 68 patients with delTyr (n=26) or delWK (n=42) were reviewed and compared. RESULTS: GISTs with delTyr were more frequently extragastric than those with delWK (69 vs 26%, P<0.0005). After curative surgery, median relapse-free survival were 10.8 and 11.1 months for patients with delTyr (n=14) and delWK (n=29), respectively (P=0.92). All patients treated with imatinib for a non-resectable or metastatic GIST had an objective response (n=15) or a stable disease (n=21) as best response, regardless of mutation. Median progression-free survival with imatinib were 21.9 and 18.9 months for patients with GIST with delTyr (n=14) and delWK (n=22), respectively (P=0.43). CONCLUSION: In this large retrospective series, the type of KIT exon 11 mutation was correlated with the origin of GIST, but not with prognosis or response to imatinib.

Mild dehydrated hereditary stomatocytosis revealed by marked hepatosiderosis.

We report a patient in whom hepatosiderosis was diagnosed at the age of 55 years and who has since been treated by regular bleeding. The H63D mutation was found in the heterozygous state in the HFE gene. No mutation was recorded in the SLC11A3 gene (ferroportin). Hepatosiderosis did not seem primary, nevertheless its cause long remained elusive. Only 2 years ago did we find the responsible condition, a very mildly expressed form of dehydrated hereditary stomatocytosis (DHS). This genetic disease is a strongly iron-loading condition. Haemolysis was fully compensated. Kalaemia was slightly elevated, suggesting a pseudohyperkalaemia that may be associated with DHS. Osmotic gradient ektacytometry allowed to assess the diagnosis of DHS. The red cell monovalent Na+ and K+ concentrations were moderately elevated and reduced respectively. The temperature dependence of the ouabain + bumetanide-resistant K+ influx produced a shallow slope, above and parallel to the control curve. These features were consistent with the diagnosis of DHS. The pronounced hepatosiderosis contrasted with the mildly expressed DHS, and with the ferritinaemia that was slightly elevated, if at all, prior to bleeding. Bleeding caused ferritinaemia to decrease and hepatosiderosis to recede. The whole picture accounts for a misleading presentation of DHS, in which the primary condition long remained hidden behind one of its remotest complications, hepatosiderosis.

Comparison of the cytotoxic effects of corticoids on the neoplastic B cells.

Many clinical trials have been engaged to prove the benefits of new drugs in the treatment of hematological tumours. However, no real progress have occurred in diseases such as multiple myeloma, the association of melphalan and prednisone is still the mainstay of the treatment. During all these years, the family of glucocorticoids have not been totally studied. Their efficiency in the cure of lymphoid malignancies has been early recognised, but still to be based on their anti-inflammatory potency for the dosages. Only few works reported the comparison between members of this family. We demonstrate in this work, in vitro, with a cell line of medium sensibility and a B cell of tumoral origin grew up in our laboratory, that exists some differences in the anti-neoplastic potency of the more commonly used corticoids. If the order in which we can class these drugs is not surprising and empirically known, the importance of the differences observed need a special attention. We also found that these drugs might have stimulatory effects, at various degree in function of their concentrations, on the proliferation of the B cell lines. Theses side effects coupled to the efficiency variations of each corticoid present the need of paying more attention to the choice of the molecule implied in the chemotherapy.

[Treatment of polycythemia. II.--Comparison of hydroxyurea with pipobroman in 294 patients less than 65 years of age]. / Traitement des polyglobulies. II.--Comparaison de l'hydroxyurée et du pipobroman chez 294 malades âgés de moins de 65 ans.

AIMS: To compare by a prospective study in low risk polycythemia vera (PV) patients alone two drugs: hydroxyurea and pipobroman. Toxicity, efficiency, and leukemogenic potential were studied. PATIENTS: 294 patients with a documented PV, aged less than 65 years, have been included since 1980 in a prospective study comparing hydroxyurea and pipobroman. Blood cell counts were performed every two months and a clinical evaluation by a specialist was obtained every four or six months. RESULTS: Hematologic toxicity of both drugs was higher than expected, requiring strict surveillance. These drugs were tolerated in some (gastric pain and diarrhea on pipobroman, buccal aphtosis and chronic leg ulcers on hydroxyurea), leading to a change of arm in 10% of the cases. Hydroxyurea did not control the megakaryocitic hyperplasia in 40% of the cases, which probably explains a high rate of progression to myelofibrosis with myeloid metaplasia in this arm. Both drugs were leukemogenic with an actuarial risk of about 15% at the 15th year, not significantly lower than that observed in the 32P treated patients. A significant risk of cutaneous malignancy was observed in the hydroxyurea arm. The mean expectancy of life cannot yet be accurately evaluated, but seems significantly lower than that of the reference population. CONCLUSION: The treatment of PV by hydroxyurea or pipobroman has to account for these results less optimistic than those traditionally well-known to hematologists and internists.

High-dose salvage chemotherapy without bone marrow transplantation for adult patients with refractory Hodgkin's disease.

PURPOSE: For patients with Hodgkin's disease (HD) who do not achieve complete response (CR), who experience a relapse within the first year of CR, and for those who have two or more relapses, the outcome is poor. Salvage chemotherapy regimens at conventional doses produce a CR rate that ranges from 10% to 50% and a 5-year disease-free survival (DFS) between 10% and 25%. On the other hand, high-dose chemotherapy regimens given in combination with bone marrow transplantation (BMT) produce a CR rate that ranges from 40% to 80% and a 3-year DFS of approximately 40%. We report the 5-year results of a prospective study in patients with refractory HD who were treated with three courses of intensive chemotherapy without BMT. PATIENTS AND METHODS: Thirty-nine adult patients with refractory HD were treated with three courses of intensive chemotherapy. Each cycle of chemotherapy comprised vindesine 1 mg/m2/d in continuous intravenous (IV) infusion from day 1 to day 5; Adriamycin (doxorubicin; Roger Bellon Laboratories, Neuilly, France) 40 mg/m2/d in continuous IV infusion from day 1 to day 3; carmustine 140 mg/m2/d at day 3; etoposide 200 mg/m2/d from day 3 to day 5; and methylprednisolone 120 mg/m2/d from day 1 to day 5. After the third cycle of chemotherapy, irradiation (20 Gy) was performed whenever possible and depended on previous irradiation. RESULTS: At the end of the treatment, 31 patients (79%) were in CR. Among these patients, 10 relapsed after a median time of 3 months. The overall 5-year survival rate was 46%. The freedom from progression (FFP) and the freedom from treatment failure (FFTF) rates were 48% and 43%, respectively. The main toxicities were hematologic (neutropenia and thrombocytopenia) and digestive. Four patients died due to treatment-related complications (two from septic shocks, one from respiratory insufficiency, and one from posttransfusional AIDS). CONCLUSION: The results of this study seem to be comparable to those results obtained with high-dose chemotherapies with autologous BMT.