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Structural and optical properties of InAlAs/GaAlAs quantum dots grown by molecular beam epitaxy are studied using transmission electron microscopy and temperature- and time-resolved photoluminescence. The control of the recombination lifetime (50 ps-1.25 ns) and of the dot density (5.10-8-2.1011 cm-3) strongly suggest that these material systems can find wide applications in opto-electronic devices as focusing non-linear dispersive materials as well as fast saturable absorbers. [ABSTRACT FROM AUTHOR]

Abstract: The incidence of venous thromboembolism in multiple myeloma depends on the disease characteristics that include recent diagnosis, persistent or recurrent multiple myeloma, patient characteristics, and the type of treatment received such as thalidomide or lenalidomide especially in combination with high-dose dexamethasone, or combined chemotherapy. Currently, recommendations could be challenged by the results of the first randomized study evaluating aspirin, low molecular weight heparins and vitamin K antagonists in the antithrombotic prophylaxis. The recent data from the literature show that it is not possible to propose a therapeutic management for venous thromboembolism prophylaxis in multiple myeloma and that the use of antithrombotic prophylaxis may not be mandatory. [Copyright &y& Elsevier]

Summary: Aims of the study: To evaluate post-operative complications and the recurrence rate after repair of large ventral incisional hernia with an open technique using intraperitoneal composite mesh and an associated aponeurotic overlay. Patients and methods: This prospective study included a total of 280 patients who underwent repair of large incisional hernia using Parietex® composite mesh. Results: The post-operative mortality rate was 0.35%. Six patients (2%) developed subcutaneous surgical site infection without infection of the prosthesis. Six other patients (2%) developed a deep-seated infection; in three cases, the mesh had to be removed. Nine patients (3.2%) developed recurrent incisional hernia. Conclusion: Large ventral incisional hernias can be effectively treated by the intraperitoneal placement of Parietex® composite mesh overlaid by an aponeurotic graft; the incidence of complications in this prospective study was very low. [ABSTRACT FROM AUTHOR]

The article reports that fast recovery time is a key parameter for the design of new high transmission rate optical devices, like ultrafast optical switches for telecommunication applications. Optical switches can consist of semiconductor saturable absorbers that regenerate the optical signal by excitonic absorption in a QW-based structure. To reach high transmission capacity, the essential parameter for saturable absorbers is the recovery time after absorption, which is governed by the carrier recombination rate and is typically around a few ns for semiconductors.

A correction to the article "High Density InAlAs/GaAlAs Quantum Dots for Non-linear Optics in Microcavities," by R. Kuszelewicz and colleagues is presented.

Introduction: Therapeutic approaches in Multiple Myeloma (MM) have considerably changed over the last few years, with effective oral chemotherapy and continuous treatment. In this context, the objective of this study was to examine the circuitry of an advanced practitioner nurse (APN)-led intervention that provided supportive care for MM patients treated with oral chemotherapy., Methods: This population-based study was conducted at the hematology department - Institut de Cancérologie Lucien Neuwirth (ICLN, Saint-Priest-en-Jarez), from April 2017 to September 2020. A follow-up program was established with a specialized APN in oncology., Results: All APN interventions were recorded, representing 1240 phone calls and 162 consultations for 42 MM patients. Eighty-two calls were referred to the physician with 45 consultations triggered. Most of the calls were frequent within the few first months, with a high request for information and reassurance, especially for treatment-naive or relapsed patients. In our study, the APN was able to manage multiple side effects through care organization (i.e., hospitalizations, transfusions) and a careful coordination between the primary care team and the hospital., Discussion: In order to respond to the high need for care pathway and safety improvement, especially in elderly population, we have initiated an original follow-up by an APN for MM patients treated with oral chemotherapy. While the role of APN has become prominent in the oncology field in recent years, its holistic approach has to be emphasized in further studies to bring a comprehensive perspective to health care coordination in the future., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

High-dose melphalan (HDM) and transplantation are recommended for eligible patients with multiple myeloma. No other conditioning regimen has proven to be more effective and/or safer. We previously reported in a phase 2 study that bortezomib can safely and effectively be combined with HDM (Bor-HDM), with a 32% complete response (CR) rate after transplantation. These data supported a randomized phase 3 trial. Randomization was stratified according to risk and response to induction: 300 patients were enrolled, and 154 were allocated to the experimental arm (ie, arm A) with bortezomib (1 mg/m2 intravenously [IV]) on days -6, -3, +1, and +4 and melphalan (200 mg/m2 IV) on day -2. The control arm (ie, arm B) consisted of HDM alone (200 mg/m2 IV). There were no differences in stringent CR + CR rates at day 60 posttransplant (primary end point): 22.1% in arm A vs 20.5% in arm B (P = .844). There were also no differences in undetectable minimum residual disease rates: 41.3% vs 39.4% (P = .864). Median progression-free survival was 34.0 months for arm A vs 29.6 months for arm B (adjusted HR, 0.82; 95% CI, 0.61-1.13; P = .244). The estimated 3-year overall survival was 89.5% in both arms (hazard ratio, 1.28; 95% CI, 0.62-2.64; P = .374). Sixty-nine serious adverse events occurred in 18.7% of Bor-HDM-treated patients (vs 13.1% in HDM-treated patients). The proportion of grade 3/4 AEs was similar within the 2 groups (72.0% vs 73.1%), mainly (as expected) blood and gastrointestinal disorders; 4% of patients reported grade 3/4 or painful peripheral neuropathy in arm A (vs 1.5% in arm B). In this randomized phase 3 study, a conditioning regimen with Bor-HDM did not improve efficacy end points or outcomes compared with HDM alone. The original trial was registered at www.clinicaltrials.gov as #NCT02197221., (© 2022 by The American Society of Hematology.)

Purpose: The use of oral cancer drugs (OAD) has increased over the last two decades. The objective of this study was to measure the impact of a nurse-led telephone follow-up in the therapeutic management of patients treated with an OAD regarding toxicity, medication adherence and quality of life., Methods: A randomized, multicenter, controlled trial was conducted. All consecutive over 18-year-old patients, treated in medical oncology, radiotherapy, or hematology departments, receiving OAD for any cancer were invited to participate to the study. A total of 183 patients treated for solid or hematological cancers with an OAD were randomly assigned to receive a nurse-led telephone follow-up or standard care for 24 weeks. Data were collected between 2015 and 2018., Results: Nurse telephone follow-up did not improve the global score toxicity in the intervention group. However, telephone calls directed by trained nurses induced a significant decrease in number of patients with grade 3 adverse events throughout the follow-up [OR 0.45 (IC à 95%) (0.23, 0.9)](P = 0.03). There was no significant difference in quality of life and medication adherence between groups at any follow-up time point., Conclusions: In this first French real-life study, the advice provided by qualified nurses via phone calls improved the management of grade 3 toxicities but failed to demonstrate an improvement of all grades of toxicities. More prospective studies are needed to confirm the impact of telephone calls on the toxicities related to OAD., Trial Registration: Clinical trial registration is NCT02459483. Protection committee SUD-ESTI registration is 2015-A00527-42 on 13 April 2015. National Agency for the Safety of Medicines and Health Products registration is 150619-B on the 27 may 2015.

Background: Acute kidney injury (AKI) is a public health concern. Among the pathological situations leading to AKI, drugs are preventable factors but are still under-notified. We aimed to provide an overview of drug-induced AKI (DIAKI) using pharmacovigilance and medical administrative databases Methods: A query of the PMSI database (French Medical Information System Program) of adult inpatient hospital stays between 1 January 2017 and 31 December 2018 was performed using ICD-10 (International Classification of Diseases 10th revision) codes to identify AKI cases which were reviewed by a nephrologist and a pharmacovigilance expert to identify DIAKI cases. In parallel, DIAKIs notified in the French Pharmacovigilance Database (FPVDB) were collected. A capture-recapture method was performed to estimate the total number of DIAKIs., Results: The estimated total number of DIAKIs was 521 (95%CI 480; 563), representing 20.0% of all AKIs. The notification was at a rate of 12.9% (95%CI 10.0; 15.8). According to the KDIGO classification, 50.2% of the DIAKI cases were stage 1 and 49.8% stage 2 and 3. The mortality rate was 11.1% and 9.6% required hemodialysis., Conclusion: This study showed that drugs are involved in a significant proportion of patients developing AKI during a hospital stay and emphasizes the severity of DIAKI cases.

Purpose: We report a multicenter controlled trial comparing renal recovery and tolerance profile of doublet versus triplet bortezomib-based regimens in patients with initial myeloma cast nephropathy (CN) and acute kidney injury (AKI) without need for dialysis., Methods: After symptomatic measures and high-dose dexamethasone, patients were randomly assigned to receive bortezomib plus dexamethasone (BD), or BD plus cyclophosphamide (C-BD). In patients with < 50% reduction of serum free light chains (sFLCs) after 3 cycles, chemotherapy was reinforced with either cyclophosphamide (BD group) or thalidomide (C-BD group)., Results: Ninety-two patients were enrolled in each group. At random assignment, characteristics of the 2 groups were similar, including median age (68 years) and serum creatinine level (305.5 and 273.5 µmol/L in BD and C-BD group, respectively). At 3 months, renal response rate (primary end point) was not different (41 v 47 responders in the BD and C-BD groups, respectively; relative risk [RR], 0.87; P = .46). Very good partial response (free light chain reduction ≥ 90%) or more was achieved in 36 and 47 patients, respectively (RR, 0.76; P = .10). After 1 cycle of chemotherapy, 69 in the BD group and 67 patients in the C-BD group had achieved sFLC level ≤ 500 mg/L. Serious adverse events were recorded in 30 and 40 patients, respectively. At 12 months, 19 patients had died (9 in the BD group v 10 in the C-BD group), including 10 (6 in the BD group and 4 in the C-BD group) from myeloma progression and 3 (0 in the BD group and 3 in the C-BD group) from infection. Within median follow-up of 27 months, 43 and 42 patients switched to new therapy, respectively. Overall, 50 patients (24 in the BD group and 26 in the C-BD group) had died., Conclusion: This randomized study did not show any benefit of C-BD compared with BD on renal recovery of patients with initial CN not requiring dialysis. Adding cyclophosphamide did not sufficiently improve the efficacy-toxicity balance. Patients with myeloma with AKI are fragile, and indication for doublet or triplet regimen should be adapted to frailty.

Objectives: to prospectively evaluate the incidence and the clinical relevance on hematopoietic reconstitution of HHV-6 infection in autologous hematopoietic stem cell transplantation (ASCT) recipients., Methods: HHV-6 DNA load was measured in whole blood specimens once during the 7 days before stem cell re-infusion and once a week after transplantation until hematopoietic recovery. Active HHV-6 infection was defined by 2 consecutive positive DNA loads., Results: from July 2012 to February 2015, 196 adult patients undergoing ASCT were enrolled. Twenty-two (11.2%) patients developed active HHV-6 infection with a cumulative incidence of 19% at 40 days after transplantation. The onset of active HHV-6 infection occurred with a median of 13 days after stem cell re-infusion. HHV-6 infection was associated with an increased frequency of non-infectious complications (OR = 5.05; 95%CI 1.78-14.32; P < 0.001). Moreover, the severity of these non-infectious complications was higher in recipients exhibiting HHV-6 infection (OR = 4.62; 95%CI 1.32-16.2; p < 0.01). Delayed neutrophils 10 (IQR: 8-14) vs 8 (IQR: 6-11) days and platelets recoveries 15 (IQR: 11.8-18.5) vs 8 (IQR: 4-14) days were observed in patients with active HHV-6 infection compared to non-infected ones., Conclusions: in this study, 11.2% ASCT recipients presented active HHV-6 infection associated with significantly delayed hematologic reconstitution., (Copyright © 2019. Published by Elsevier Ltd.)

Renal impairment is a common complication of multiple myeloma (MM), accounting for 20-30% of MM patients at diagnosis and 40-50% of patients during the course of their disease. This feature is associated with poor prognosis and shorter survival as compared to patients with normal renal function (NRF). Therefore, therapeutic management is challenging as autologous stem cell transplantation (ASCT) is often not considered as a valuable strategy, mainly due to concerns of toxicity. In this retrospective and multicenter study, we included 55 MM patients with dialysis-dependent or independent renal failure who underwent high-dose melphalan-based ASCT in order to assess the efficacy outcomes and toxicities of this strategy. Response to ASCT was at least VGPR (very good PR) in 58% of patients and 96% of patients who also received bortezomib-based induction were at least in PR after ASCT. Median OS was 76 months and median PFS was 55 months, similarly to MM patients with NRF. In multivariate analysis, dose of melphalan (140 mg/m 2 ) was correlated with better PFS (18 months, P = 0.005). Toxicities included febrile neutropenia (75%) and severe mucositis (34%). Overall, this work confirmed that ASCT conditioned by 140 mg/m 2 melphalan is a beneficial procedure for MM patients with renal failure.

Background and Objective: Vitamin D supplementation in preterm infants has been recommended by American Academy of Pediatrics (AAP); however, its efficacy and safety has not been well studied. To study 25-hydroxy vitamin D (25OHD) levels as a marker of vitamin D status of very low birth weight infants while on vitamin D supplementation during neonatal intensive care unit hospitalization., Methods: Retrospective study of preterm infants with birth weight <1500 g admitted to our unit from January 2013 to December 2015 who were on oral vitamin D3 400 IU supplementation. Serum 25OHD level were checked at 4, 8, and 12 weeks of age or before discharge and the levels were stratified as deficient <20 ng/mL, insufficient 20 to 29 ng/mL, normal 30 to 60 ng/mL, high 61 to 100 ng/mL and very high >100 ng/mL., Results: A total of 301 infants were enrolled, 186 very low birth weight (VLBW; 1000-1499 g) infants and 115 extremely low birth weight (ELBW; <1000 g) infants. Approximately 80% of both VLBWs and ELBWs had deficient or insufficient 25OHD levels at 4 weeks of age. On oral vitamin D supplementation, VLBW infants increased their 25OHD levels significantly by 8 and 12 weeks of age, whereas ELBW infants lagged behind at 8 weeks and increased their 25OHD levels by 12 weeks of age., Conclusions: Eighty percent of ELBW and VLBW infants have either deficient or insufficient vitamin D status at 4 weeks of age. Vitamin D supplementation helps in improving the vitamin D levels, VLBW infants significantly more than ELBW infants. AAP recommendation appears to be safe; however, if using higher supplement dosing, 25OHD level should be monitored to avoid high and very high vitamin D levels.

Importance: Cast nephropathy is the main cause of acute kidney injury in multiple myeloma and persistent reduction in kidney function strongly affects prognosis. Strategies to rapidly remove nephrotoxic serum-free light chains combined with novel antimyeloma agents have not been evaluated prospectively., Objective: To compare the hemodialysis independence rate among patients newly diagnosed with myeloma cast nephropathy treated with hemodialysis using a high-cutoff dialyzer (with very large membrane pores and high permeability to immunoglobulin light chains) or a conventional high-flux dialyzer (with small pores and lower permeability)., Design, Setting, and Participants: Randomized clinical trial involving 98 patients with biopsy-proven myeloma cast nephropathy requiring hemodialysis treated at 48 French centers between July 2011 and June 2016; the final date of follow-up was June 29, 2016., Interventions: Intensive hemodialysis (eight 5-hour sessions over 10 days) with either a high-cutoff dialyzer (46 patients) or a conventional high-flux dialyzer (48 patients). All patients received the same chemotherapy regimen of bortezomib and dexamethasone., Main Outcomes and Measures: Primary end point was hemodialysis independence at 3 months; secondary end points: hemodialysis independence rates at 6 and 12 months, hemodialysis- and chemotherapy-related adverse events, and death., Results: Among 98 randomized patients, 94 (96%) (median age, 68.8 years [interquartile range, 61.2-75.3 years]; 45% women) were included in the modified intent-to-treat analysis. The hemodialysis independence rate at 3 months was 41.3% (n = 19) in the high-cutoff hemodialysis group vs 33.3% (n = 16) in the conventional hemodialysis group (between-group difference, 8.0% [95% CI, -12.0% to 27.9%], P = .42); at 6 months, the rate was 56.5% (n = 26) vs 35.4% (n = 17), respectively (between-group difference, 21.1% [95% CI, 0.9% to 41.3%], P = .04); and at 12 months, the rate was 60.9% (n = 28) vs 37.5% (n = 18) (between-group difference, 23.4% [95% CI, 3.2% to 43.5%], P = .02). The incidence of hemodialysis-related adverse events was 43% in the high-cutoff hemodialysis group vs 39% in the conventional hemodialysis group; chemotherapy-related serious adverse events, 39% vs 37%, respectively; and at 12 months, 9 patients vs 10 patients died., Conclusions and Relevance: Among patients with myeloma cast nephropathy treated with a bortezomib-based chemotherapy regimen, the use of high-cutoff hemodialysis compared with conventional hemodialysis did not result in a statistically significant difference in hemodialysis independence at 3 months. However, the study may have been underpowered to identify an early clinically important difference., Trial Registration: clinicaltrials.gov Identifier: NCT01208818.

Colorectal cancers (CRCs) displaying microsatellite instability (MSI) most often result from MLH1 deficiency. The aim of this study was to assess the impact of MLH1 expression per se on tumor evolution after curative surgical resection using a xenograft tumor model. Transplantable tumors established with the human MLH1-deficient HCT116 cell line and its MLH1-complemented isogenic clone, mlh1-3, were implanted onto the caecum of NOD/SCID mice. Curative surgical resection was performed at day 10 in half of the animals. The HCT116-derived tumors were more voluminous compared to the mlh1-3 ones (P = .001). Lymph node metastases and peritoneal carcinomatosis occurred significantly more often in the group of mice grafted with HCT116 (P = .007 and P = .035, respectively). Mlh1-3-grafted mice did not develop peritoneal carcinomatosis or liver metastasis. After surgical resection, lymph node metastases only arose in the group of mice implanted with HCT116 and the rate of cure was significantly lower than in the mlh1-3 group (P = .047). The murine orthotopic xenograft model based on isogenic human CRC cell lines allowed us to reveal the impact of MLH1 expression on tumor evolution in mice who underwent curative surgical resection and in mice whose tumor was left in situ. Our data indicate that the behavior of MLH1-deficient CRC is not only governed by mutations arising in genes harboring microsatellite repeated sequences but also from their defect in MLH1 as such., (© 2017 Wiley Periodicals, Inc.)

Thioacidolysis is a method used to measure the relative content of lignin monomers bound by β-O-4 linkages. Current thioacidolysis methods are low-throughput as they require tedious steps for reaction product concentration prior to analysis using standard GC methods. A quantitative thioacidolysis method that is accessible with general laboratory equipment and uses a non-chlorinated organic solvent and is tailored for higher-throughput analysis is reported. The method utilizes lignin arylglycerol monomer standards for calibration, requires 1-2 mg of biomass per assay and has been quantified using fast-GC techniques including a Low Thermal Mass Modular Accelerated Column Heater (LTM MACH). Cumbersome steps, including standard purification, sample concentrating and drying have been eliminated to help aid in consecutive day-to-day analyses needed to sustain a high sample throughput for large screening experiments without the loss of quantitation accuracy. The method reported in this manuscript has been quantitatively validated against a commonly used thioacidolysis method and across two different research sites with three common biomass varieties to represent hardwoods, softwoods, and grasses., (© 2016 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

It is unknown how often preterm infants in neonatal intensive care units achieve the American Academy of Pediatrics-recommended daily intake of 400 international units of Vitamin D. We studied 378 preterm infants with birth weight 1500 g or less admitted to our neonatal intensive care unit, 151 infants before and 227 infants after daily vitamin D-intake monitoring was introduced. Infants were stratified into 2 groups: extremely low birth weight (<1000 g) and Very low birth weight (1000-1500 g). Monitoring of daily intake coincided with significant improvement in vitamin D intake in both extremely low birth weight and very low birth weight groups.

Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often proposed for patients with comorbidities. To enhance engraftment and limit graft-versus-host disease (GVHD), antithymoglobulin (ATG) is usually used. However, the dose needed remains unclear unlike myeloablative conditioning. In order to clarify this point, we conducted a retrospective study on patients who received a reduced intensity conditioning allo-HSCT based on a 2-day fludarabine and busulfan treatment with either 1 or 2 days of ATG treatment. One hundred and eight patients received 2.5 mg/kg (ATG2.5) and another 60 patients 5 mg/kg (ATG5). The median follow-up was 36 months. The median overall survival was 39 months and the median disease-free survival 45 months. In multivariate analysis, overall nonrelapse mortality (NRM) was independently influenced by the acute GVHD grade III-IV (p < 0.001) and ATG dose (30 vs. 21% for ATG5; p = 0.008). Despite heterogeneity of populations, using proportional-hazard assumptions, we have been able to observe in multivariate analysis a lower NRM in the ATG5 group. This leads to a statistically higher overall survival for the ATG5 group. In conclusion, 2 days of ATG decrease NRM independently without increasing the risk of relapse or infectious disease., (© 2016 S. Karger AG, Basel.)

Bicalutamide (Casodex(®) ) is a non-steroidal pure anti-androgen used in the treatment of localized prostate cancer. It is a racemate drug, and its activity resides in the (R)-enantiomer, with little in the (S)-enantiomer. A major metabolic pathway for bicalutamide is glucuronidation catalysed by UDP-glucuronosyltransferase (UGT) enzymes. While (S)bicalutamide is directly glucuronidated, (R)bicalutamide requires hydroxylation prior to glucuronidation. The contribution of human tissues and UGT isoforms in the metabolism of these enantiomers has not been extensively investigated. In this study, both (R) and/or (S)bicalutamide were converted into glucuronide (-G) derivatives after incubation of pure and racemic solutions with microsomal extracts from human liver and kidney. Intestinal microsomes exhibited only low reactivity with these substrates. Km values of liver and kidney samples for (S)bicalutamide glucuronidation were similar, and lower than values obtained with the (R)-enantiomer. Among the 16 human UGTs tested, UGT1A8 and UGT1A9 were able to form both (S) and (R)bicalutamide-G from pure or racemic substrates. UGT2B7 was also able to form (R)bicalutamide-G. Kinetic parameters of the recombinant UGT2B7, UGT1A8 and UGT1A9 enzymes support a predominant role of the UGT1A9 isoform in bicalutamide metabolism. Accordingly, (S)bicalutamide inhibited the ability of human liver and kidney microsomes to glucuronidate the UGT1A9 probe substrate, propofol. In conclusion, the present study provides the first comprehensive analysis of in vitro bicalutamide glucuronidation by human tissues and UGTs and identifies UGT1A9 as a major contributor for (R) and (S) glucuronidation in the human liver and kidney., (© 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.)

The incidence of venous thromboembolism in multiple myeloma depends on the disease characteristics that include recent diagnosis, persistent or recurrent multiple myeloma, patient characteristics, and the type of treatment received such as thalidomide or lenalidomide especially in combination with high-dose dexamethasone, or combined chemotherapy. Currently, recommendations could be challenged by the results of the first randomized study evaluating aspirin, low molecular weight heparins and vitamin K antagonists in the antithrombotic prophylaxis. The recent data from the literature show that it is not possible to propose a therapeutic management for venous thromboembolism prophylaxis in multiple myeloma and that the use of antithrombotic prophylaxis may not be mandatory., (Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Purpose: HSP90 targeting is a promising therapeutic approach in cancer. 17-AAG is an HSP90 inhibitor with completed Phase I trials in patients with advanced cancer and recently published Phase II trials. The aim of this work was to study the expression of HSP 90 and apoptotic proteins, the effects in culture of 17-AAG on cell survival and apoptosis and to compare Philadelphia-positive (Ph+) ALL to common B cell ALL, in ALL cell lines and in patients' cells collected at ALL diagnosis., Methods: We analysed 2 ALL cell lines and 63 leukaemic samples from patients treated in our institution (44 common B cell ALL and 19 Ph+ ALL). We performed flow cytometry analysis of bone marrow aspiration and cell lines with a combination of anti-HSP90, Bax, Bcl-2 and Bcl-xl antibodies. Apoptosis after cell culture (in presence or not of 17-AAG) was assessed using Annexin V and activated caspase-3 staining., Results: Ph+ ALL cells appeared to be more sensitive to 17-AAG cytotoxicity with a 100 % mortality rate after exposure to 10 μM for 24 h (vs. 62 % for B-common ALL). A high percentage of HSP90-positive cells (in Ph+ ALL samples) was associated with high sensitivity to 17-AAG. 17-AAG induced apoptosis in a dose-dependent manner and was associated with down-regulation of Bcl-2 and Bcl-Xl expression and up-regulation of Bax expression., Conclusion: Considering that Bcr-Abl constitutes HSP 90 substrates, HSP 90 inhibition could be of particular interest for Ph+ ALL disease, even in patients harbouring resistance to tyrosine kinase inhibitor therapy.

Background: Microsatellite instability (MSI) constitutes an important oncogenic molecular pathway in colorectal cancer (CRC), representing approximately 15% of all colorectal malignant tumours. In roughly one third of the cases, the underlying DNA mismatch repair (MMR) defect is inherited through the transmission of a mutation in one of the genes involved in MMR, predominantly MSH2 and MLH1, or less frequently, MSH6 or PMS2. In the overwhelming number of sporadic cases, MSI results from epigenetic MLH1 silencing through hypermethylation of its promoter. MMR deficiency promotes colorectal oncogenesis through the accumulation of numerous mutations in crucial target genes harbouring mononucleotide repeats, notably in those involved in the control of cell proliferation and differentiation, as well as DNA damage signalling and repair., Design: In this review, we describe the molecular aspects of the MMR system and the biological consequences of its defect on the oncogenic process, and we discuss the various experimental systems used to evaluate the efficacy of cytotoxic drugs on MSI colorectal cells lines. There is increasing evidence showing that MSI CRCs differ from all CRCs in terms of prognosis and response to the treatment. We report the clinical studies that have evaluated the prognostic and predictive value of MSI status on clinical outcome in patients treated with various chemotherapy regimens used in the adjuvant setting or for advanced CRCs., Conclusion: In view of this, the opportunity of a systematic MSI phenotyping in the clinical management of patients with CRC is further discussed.

Background: Various surgical procedures have been described in the treatment of small ventral abdominal wall hernias. Mesh repair is becoming popular because of a low recurrence rate., Aim: The aim of this prospective study was to evaluate an open intraperitoneal technique using the Bard Ventralex hernia patch in the treatment of small midline ventral hernias., Methods: 101 patients were operated on (59 male, 42 female) with a mean age of 54.5 years (range 17-85). Mean operative time was 33 min (range 16-65). The median hospital stay was 2 days (range 1-15)., Results: Two patients had a hematoma without wound infection. There were 2 recurrences (2%). Mean postoperative follow-up time was 28.5 months (range 6-55)., Conclusions: Our preliminary results suggest that Ventralex hernia patch repair for ventral hernias can be performed with minimal postoperative morbidity and a low recurrence rate., (Copyright © 2010 S. Karger AG, Basel.)

The increasing frequency of EP and the need for its early diagnosis have focused our interest on the research of biochemical markers. We have established hormonal values in the plasma of 99 spontaneous ongoing pregnancies between the 4th and 10th weeks of amenorrhea, in 21 EPs, and 20 cases of early abortion. We have examined the predictive values of trophoblastic and CL production in pathological pregnancies. The association of low hCG and low active renin appears to be able to discriminate between ectopic and abortive spontaneous gestations.

The neonatal piglet is a satisfactory model for the human neonate requiring total parenteral nutrition (TPN). Bile status and subsequent liver and gallbladder dysfunction have long been documented as serious complications of long-term TPN. The purpose of this study was to determine whether small amounts of enteral formula during TPN will maintain normal bile appearance and composition. Thirty-one Hanford miniswine, 3 to 6 days old underwent surgery for the placement of central venous catheters. Two days postoperatively, the animals were separated into three groups, according to dietary regimens. Group 1 (n = 10), the control group, received pig formula (SPF-lac) orally (200 cal/kg/d); group 2 (n = 11), was maintained on TPN (180 cal/kg/d) with an enteral supplement of SPF-lac (20 cal/kg/d); group 3 (n = 10), was maintained on TPN only (200 cal/kg/d). The TPN formula consisted of 35 g/kg/d of glucose, 10 g/kg/d of protein, and 3 g/kg/d of lipid. The animals were maintained on these diets for 6 weeks. At necropsy, gallbladder with bile was weighed and bile volume and appearance was recorded. Chemical analyses was performed on 26 bile samples. Gallbladder weight was significantly decreased in groups 2 and 3 compared with group 1 (P less than .0003, P less than .033, respectively, using Students t test with Bonferoni adjustment). Volume was significantly decreased only in group 2 (P less than .003). Group differentiation in relation to bile appearance was determined by the presence or absence of either bile sludge or crystals.(ABSTRACT TRUNCATED AT 250 WORDS)

This work is a report on the follow-up of 50 pregnant epileptic women who were looked after in the Gynaecological and Obstetric Service of La Pitié-Salpêtrière in Paris. These patients had a generalised form of the disease. Well controlled patients usually had simple pregnancies. On the other hand half of those who had frequent attacks were worse during the pregnancy. It is rare for complications to occur either in the mothers or the neonates. The element that is most serious is the risk of malformation, which is three times as great whatever treatment is used and it does seem to increase according to the number of attacks occurring during the pregnancy. It therefore seems important that all epileptics should be stabilised before each pregnancy and medication should be given and controlled. It is important all the same that these are at-risk pregnancies that require clinical and ultrasound supervision.