Short duration of post-amputation antibiotic therapy in diabetic foot patients with total resection of osteomyelitis.

BACKGROUND: Short duration of post-amputation antibiotic therapy (2-5 days) is recommended in patients with diabetic foot osteomyelitis after total resection of infected bone tissue. OBJECTIVE: To evaluate the long-term effectiveness of short-duration post-amputation antibiotic therapy in diabetic patients with total resection of osteomyelitis assessed by sterile bone bacteriological samples obtained from the resection margin. METHODS: The endpoint was the absence of osteomyelitis relapse at 6 months, defined as recurrence of osteomyelitis with the need for surgical revision and/or new bone antibiotic therapy. RESULTS: Among 15 patients included, 12 (80%) were cured without recurrence of osteomyelitis at 6 months, with a mean duration of antibiotic therapy of 8.3±5.9 days post surgery. This result is comparable to literature data, while all of them reported longer duration of antibiotic therapy and/or shorter follow-up. CONCLUSION: Short duration of post-amputation antibiotic therapy in diabetic patients with sterile bacteriological samples obtained from resection margin seems effective.

3D-shape recognition and size measurement of irregular rough particles using multi-views interferometric out-of-focus imaging.

We realize simplified-tomography experiments on irregular rough particles using interferometric out-of-focus imaging. Using two angles of view, we determine the global 3D-shape, the dimensions, and the 3D-orientation of irregular rough particles whose morphologies belong to families such as sticks, plates, and crosses.

Dual-wavelength digital holography for 3D particle image velocimetry: experimental validation.

A multi-exposure digital in-line hologram of a particle field is recorded by two successive pulses of different wavelengths. During the reconstruction step, each recording can be independently analyzed by selecting a given wavelength. This procedure enables avoiding the superimposition of particle images that may be close to each other.

First application of the Automated QUantitative Analysis (AQUA) technique to quantify PTEN protein expression in ovarian cancer: A correlative study of NCIC CTG OV.16.

BACKGROUND: Platinum resistance is a dominant cause of poor outcomes in advanced ovarian cancer (OC). A mechanism of platinum resistance is the inhibition of apoptosis through phosphatidylinositol 3 kinase (PI3K) pathway activation. The role of phosphatase and tensin homolog (PTEN), a negative regulator of this pathway, as a tumor biomarker is unclear. Quantitative analysis of PTEN expression as an alternative to immunohistochemistry has not been considered. PATIENTS AND METHODS: In 238 patient tumors from the NCIC-CTG trial OV.16, PTEN protein expression was quantified by Automated QUantitative Analysis (AQUA). Cox model was used to study the association between PTEN expression and clinical outcomes using a minimum p-value approach in univariate analysis. Multivariate analysis was used to adjust for clinical and pathological parameters. RESULTS: PTEN scores (range 13.9-192.3) of the 202 samples that passed quality control were analyzed. In univariate analysis, there was a trend suggesting an association between PTEN expression by AQUA as a binary variable (low ≤61 vs high >61) and progression free survival (HR=0.77, p=0.083), and in multivariate analysis, this association approached significance (HR=0.74, p=0.059). The relationship between quantitative PTEN expression and PFS differed (p=0.01 for interaction) by the extent of surgical debulking (residual disease (RD) <1cm or ≥1cm), with a numerically superior PFS in patients with high PTEN (23.5 vs 14.9m) only when RD<1cm (p=0.19). There was no association between PTEN levels and overall survival. CONCLUSIONS: AQUA is a novel method to measure PTEN expression. Further study of PTEN as a biomarker in OC is warranted.

Simultaneous 3D location and size measurement of bubbles and sand particles in a flow using interferometric particle imaging.

We present a system to characterize a triphasic flow in a 3D volume (air bubbles and solid irregular particles in water) using only one CCD sensor. A cylindrical interferometric out-of-focus imaging setup is used to determine simultaneously the 3D position and the size of bubbles and irregular sand particles in a flow. The 3D position of the particles is deduced from the ellipticity of their out-of-focus image. The size of bubbles is deduced from analysis of interference fringes. The characteristics of irregular sand particles are obtained from analysis of their speckle-like pattern. Experiments are confirmed by simulations.

Amplified Ras-MAPK signal states correlate with accelerated EGFR internalization, cytostasis and delayed HER2 tumor onset in Fer-deficient model systems.

The non-receptor tyrosine kinase Fer belongs to a distinct subfamily of F-BAR domain containing kinases implicated in vesicular trafficking and signaling downstream of adhesion and growth factor receptors. Targeted inactivation of the fer gene in a transgenic mouse model of HER2(+), breast cancer was associated with delayed tumor onset and reduced proliferative rates in tumor cells. Fer deficiency was associated with increased rates of epidermal growth factor (EGF)-induced epidermal growth factor receptor (EGFR) internalization and amplified Ras-Raf-Mek-Erk (Ras-MAPK) signaling in primary mammary tumor epithelial cells, as well as increased cytotoxic and anti-proliferative sensitivity to the dual EGFR/HER2 inhibitor Lapatinib (LPN). These observations suggest a model in which accelerated ligand-induced EGFR internalization in Fer-deficient cells hypersensitizes the Ras-MAPK pathway to EGF, resulting in MAPK signal amplification to levels that induce cytostasis, rather than proliferation. Thus, Ras-MAPK cytostatic signaling delays HER2 tumor initiation and increases LPN cytotoxicity in Fer-deficient model systems. Taken together, these data suggest that targeting Fer alone, or in combination with LPN, may be of therapeutic benefit in HER2(+) breast cancer.

Severe acute hepatitis E in an HIV infected patient: Successful treatment with ribavirin.

In industrialized countries, most cases of hepatitis E virus (HEV) infection in humans are autochthonous, mainly through foodborne and zoonotic transmission routes. In Europe, genotype 3 is a cause of acute self-limiting viral hepatitis, but can also be responsible for chronic hepatitis in immunocompromised patients. Ribavirin has been successfully used in the treatment of chronic hepatitis E and in a few cases of severe acute hepatitis E in immunocompetent patients. We report here the case of a 39 year-old man infected with HIV presenting with acute hepatitis E (genotype 3c). Unlike most cases, evolution was severe with a fall of prothrombin time down to 45%. Treatment with ribavirin allowed rapid viral clearance and a gradual normalization of liver function tests.

Long time exposure digital in-line holography for 3-D particle trajectography.

One advantage of digital in-line holography is the ability for a user to know the 3-D location of a moving particle recorded at a given time. When the time exposure is much larger than the time required for grabbing the particle image at a given location, the diffraction pattern is spread along the trajectory of this particle. This can be seen as a convolution between the diffraction pattern and a blurring function resulting from the motion of the particle during the camera exposure. This article shows that the reconstruction of holograms recorded under such conditions exhibit traces that could be processed for extracting 3D trajectories.

Mucinous advanced epithelial ovarian carcinoma: clinical presentation and sensitivity to platinum-paclitaxel-based chemotherapy, the GINECO experience.

BACKGROUND: Advanced mucinous epithelial ovarian carcinoma (mEOC) has been associated with a worse prognosis than the more common serous epithelial ovarian carcinomas (sEOC), but it remains unclear whether this observation reflects a more aggressive clinical presentation and/or chemoresistance. PATIENTS AND METHODS: Data from four randomized phase III and one phase II advanced epithelial ovarian carcinoma (EOC) first-line clinical trials were retrospectively collected, yielding 1118 patients with advanced EOC (International Federation of Gynecology and Obstetrics stages IIB-IV), 85% of whom were treated with paclitaxel (Taxol)-carboplatin-based chemotherapy. RESULTS: Based on 786 patients with sEOC and 54 (5%) with mEOC, peritoneal carcinomatosis were more limited in mEOC, which was more frequently stages IIB-IIIB (32% versus 19%, P = 0.001) and had more frequently macroscopic complete resection after initial surgery (50% of stages II-III versus 30%, P = 0.02). In contrast, visceral metastases (stage IV) were more frequent in mEOC (30% versus 15%, P = 0.004). mEOC had a lower response rate to carboplatin-paclitaxel, and shorter progression-free and overall survival rates, for both stage IV and optimally debulked stages II-III patients. CONCLUSIONS: Advanced mEOC appears to be highly chemoresistant and complete resection of peritoneal metastases is unable to reverse its poor prognosis. New therapeutic options are needed.

Suppression of the Moiré effect in sub-picosecond digital in-line holography.

Digital in-line holography is widely used in flow studies where the 3D position, size and velocity of particles or fibers have to be known at a given time. When holograms are recorded by using a sub-picosecond laser the enlargement of the spectral distribution acts as a spatial low-pass filter over the intensity distribution of the diffraction pattern. This is not a disadvantage as regards to the spatial sampling. Indeed, the Moiré effect, due to the sub-sampling of the fringe pattern is naturally reduced. Experimental results are provided.

Efficacy and tolerability of the ifosfamide-epirubicin combination in relapsed ovarian cancer.

A retrospective study evaluating the efficacy and tolerability of epirubicin-ifosfamide (EI) in patients with relapsed advanced ovarian cancer (ROC) after prior chemotherapy was conducted. A total of 93 patients received epirubicin (50 mg/m(2), day 1), ifosfamide (1500 or 2500 mg/m(2), days 1-3), and mesna monthly. Thirty-five percent had received one line of chemotherapy (platinum 100%, taxanes 8%); 38%, two lines; and 27%, more than two lines. Fifty-three percent received 2500 mg/m(2)/day ifosfamide and 47% received 1500 mg/m(2)/day ifosfamide. Ifosfamide was administered by continuous infusion in 12 patients. Mean number of courses was 4 (1-12). Grade 4 toxicity was 69% neutropenia and 12% thrombocytopenia. Three patients on high-dose ifosfamide as a short infusion had central nervous system dysfunction resulting in death. There were 84 assessable patients: 7 (8%), complete responses; 13 (15%), partial responses; and 20 (24%), stable disease. Median time to progression was 5 months (3 days to 36 months). The EI combination appears to be effective in ROC. However, toxicity with high-dose ifosfamide administered by short infusion is not acceptable. Tolerability can be improved using ifosfamide at 1500 mg/m(2) by continuous infusion. The combination of ifosfamide with newer anthracycline agents such as liposomal doxorubicin may be an alternative and needs further evaluation for use after first-line taxane-based chemotherapy.

Application of the fractional Fourier transformation to digital holography recorded by an elliptical, astigmatic Gaussian beam.

The authors have studied the diffraction pattern produced by a particle field illuminated by an elliptic and astigmatic Gaussian beam. They demonstrate that the bidimensional fractional Fourier transformation is a mathematically suitable tool to analyse the diffraction pattern generated not only by a collimated plane wave [J. Opt. Soc. Am A 19, 1537 (2002)], but also by an elliptic and astigmatic Gaussian beam when two different fractional orders are considered. Simulations and experimental results are presented.

Digital in-line holography: influence of the shadow density on particle field extraction.

We have used a digital in-line holography system with numerical reconstruction for 3D particle field extraction. In this system the diffraction patterns (holograms) are directly recorded on a charge-coupled device (CCD) camera. The numerical reconstruction is based on the wavelet transformation method. A sample volume is reconstructed by computing the wavelet components for different scale parameters. These parameters are related to the axial distance between a particle and the CCD camera. The particle images are identified and localized by analyzing the maximum of the wavelet transform modulus and the equivalent diameter of the particle image. The general process for the 3D particle location and data processing method are presented. As in classical holography we found that the signal to noise ratio depends only on the shadow density. Nevertheless, we show that both the volume depth and the shadow density affect the percentage of extracted particles.

Improved technique for fluorescence in situ hybridisation analysis of isolated nuclei from archival, B5 or formalin fixed, paraffin wax embedded tissue.

Fluorescence in situ hybridisation (FISH) is an effective method to detect chromosomal alterations in a variety of tissue types, including archived paraffin wax embedded specimens fixed in B5 or formalin. However, precipitating fixatives such as B5 have been known to produce unsatisfactory results in comparison with formalin when used for FISH. This study describes an effective nuclear isolation and FISH procedure for B5 and formalin fixed tissue, optimising the nuclear isolation step and nuclei pretreatments using tonsil and mantle cell lymphoma specimens. The protocol presented can be used to isolate nuclei and perform FISH on B5 or formalin fixed, paraffin wax embedded samples from a variety of tissue types.

Characterization of chirped pulses with the fractional-order Fourier transformation.

We show that the fractional-order Fourier transformation (FRT) is a suitable method to describe chirped pulses submitted to group-velocity dispersion in a linear dispersive medium. Amplitudes exhibiting different chirp coefficients are easily separated with the FRT, although they are temporally superposed.

The leukemogenic transcription factor E2a-Pbx1 induces expression of the putative N-myc and p53 target gene NDRG1 in Ba/F3 cells.

The chimeric transcription factor E2a-Pbx1 is expressed as a result of the 1;19 chromosomal translocation in some 5% of cases of pediatric acute lymphoblastic leukemia. We investigated the biological and transcriptional consequences of forced expression of E2a-Pbx1 in the interleukin-3 (IL-3) dependent, bone marrow-derived cell line Ba/F3. We show that forced expression of E2a-Pbx1 induces apoptosis in Ba/F3 cells without apparent effects on cell cycle progression. This pro-apoptotic effect is enhanced on cytokine deprivation. Furthermore, using cDNA representational difference analysis (RDA), we show that these cellular effects are associated with marked induction of the gene NDRG1, which was previously identified as a target of transcriptional repression by N-myc and induction by the tumor suppressor protein p53. We identify a portion of the NDRG1 promoter capable of mediating transcriptional induction by E2a-Pbx1 and show that NDRG1 is also induced on simple IL-3 deprivation of BaF3 cells. Although we show that E2a-Pbx1 induction of NDRG1 is not impaired as a result of targeting p53 using HPV E6, and therefore does not appear to be p53-dependent, our results overall are consistent with the notion that induction of NDRG1 by E2a-Pbx1 may represent part of an apoptotic or cytostatic cellular response to oncogene activation.