Synthetic MRI is not yet ready for morphologic and functional assessment of patellar cartilage at 1.5Tesla.

PURPOSE: The purpose of this study was to compare morphologic assessment and relaxometry of patellar hyaline cartilage between conventional sequences (fast spin-echo [FSE] T2-weighted fat-saturated and T2-mapping) and synthetic T2 short-TI inversion recovery (STIR) and T2 maps at 1.5T magnetic resonance imaging (MRI). METHOD: The MRI examinations of the knee obtained at 1.5T in 49 consecutive patients were retrospectively studied. There were 21 men and 28 women with a mean age of 45±17.7 (SD) years (range: 18-88 years). Conventional and synthetic acquisitions were performed, including T2-weighted fat-saturated and T2-mapping sequences. Two radiologists independently compared patellar cartilage T2-relaxation time on conventional T2-mapping and synthetic T2-mapping images. A third radiologist evaluated the patellar cartilage morphology on conventional and synthetic T2-weighted images. The presence of artifacts was also assessed. Interobserver agreement for quantitative variables was assessed using intraclass correlation coefficient (ICC). RESULTS: In vitro, conventional and synthetic T2 maps yielded similar mean T2 values 58.5±2.3 (SD) ms and 58.8±2.6 (SD) ms, respectively (P=0.414) and 6% lower than the expected experimental values (P=0.038). Synthetic images allowed for a 15% reduction in examination time compared to conventional images. On conventional sequences, patellar chondropathy was identified in 35 patients (35/49; 71%) with a mean chondropathy grade of 4.8±4.8 (SD). On synthetic images, 28 patients (28/49; 57%) were diagnosed with patellar chondropathy, with a significant 14% difference (P=0.009) and lower chondropathy scores (3.7±4.9 [SD]) compared to conventional images. Motion artifacts were more frequently observed on synthetic images (18%) than on conventional ones (6%). The interobserver agreement was excellent for both conventional and synthetic T2 maps (ICC>0.83). Mean cartilage T2 values were significantly greater on synthetic images (36.2±3.8 [SD] ms; range: 29-46ms) relative to conventional T2 maps (31.8±4.1 [SD] ms; range: 26-49ms) (P<0.0001). CONCLUSION: Despite a decrease in examination duration, synthetic images convey lower diagnostic performance for chondropathy, greater prevalence of motion artifacts, and an overestimation of T2 values compared to conventional MRI sequences.

3D reconstructions, 4D imaging and postprocessing with CT in musculoskeletal disorders: Past, present and future.

Three-dimensional (3D) imaging and post processing are common tasks used daily in many disciplines. The purpose of this article is to review the new postprocessing tools available. Although 3D imaging can be applied to all anatomical regions and used with all imaging techniques, its most varied and relevant applications are found with computed tomography (CT) data in musculoskeletal imaging. These new applications include global illumination rendering (GIR), unfolded rib reformations, subtracted CT angiography for bone analysis, dynamic studies, temporal subtraction and image fusion. In all of these tasks, registration and segmentation are two basic processes that affect the quality of the results. GIR simulates the complete interaction of photons with the scanned object, providing photorealistic volume rendering. Reformations to unfold the rib cage allow more accurate and faster diagnosis of rib lesions. Dynamic CT can be applied to cinematic joint evaluations a well as to perfusion and angiographic studies. Finally, more traditional techniques, such as minimum intensity projection, might find new applications for bone evaluation with the advent of ultra-high-resolution CT scanners. These tools can be used synergistically to provide morphologic, topographic and functional information and increase the versatility of CT.

Imaging appearance and prevalence of the anteromedial meniscofemoral ligament: A potential pitfall to anterior cruciate ligament analysis on MRI.

PURPOSE: To describe the aspect of the anteromedial meniscofemoral ligament on MRI and to assess its prevalence. METHOD: One thousand five hundred sixty knee MRI studies were retrospectively evaluated for the presence of an anteromedial meniscofemoral ligament. In addition to these studies, nine full MRI studies from our department's image archive were also analysed. The anteromedial meniscofemoral ligament length, thickness, and angle with respect to the tibial plateau were evaluated independently by two radiologists. For comparison purposes, the anterior cruciate ligament was assessed in the same manner. RESULTS: There was a 0.77% prevalence of the anteromedial meniscofemoral ligament in the study population. Compared to the anterior cruciate ligament, the anteromedial meniscofemoral ligament was 80.6%-83.8% thinner according to both observers (P =  0.0002), with a mean thickness of 1.53 ±â€¯0.47 mm and 1.80 ±â€¯0.66 mm determined by observers 1 and 2, respectively. The anteromedial meniscofemoral ligament angles were 15%-17.7% lower than the anterior cruciate ligament angles (P <  0.003). Interobserver reproducibility was considered excellent for the length and angle measurements (ICCs varying from 0.85-0.97) and good for the thickness measurements (ICCs 0.66-0.77). CONCLUSIONS: The anteromedial meniscofemoral ligament is a rare structure that can be differentiated from the anterior cruciate ligament based on morphologic criteria.

Detecting abnormal thyroid cartilages on CT using deep learning.

PURPOSE: The purpose of this study was to evaluate the performance of a deep learning algorithm in detecting abnormalities of thyroid cartilage from computed tomography (CT) examination. MATERIALS AND METHODS: A database of 515 harmonized thyroid CT examinations was used, of which information regarding cartilage abnormality was provided for 326. The process consisted of determining image abnormality and, from these preprocessed images, finding the best learning algorithm to appropriately characterize thyroid cartilage as normal or abnormal. CT images were cropped to be centered around the cartilage in order to focus on the relevant area. New images were generated from the originals by applying simple transformations in order to augment the database. Characterizations of cartilage abnormalities were made using transfer learning, by using the architecture of a pre-trained neural network called VGG16 and adapting the final layers to a binary classification problem. RESULTS: The best algorithm yielded an area under the receiving operator characteristic curve (AUC) of 0.72 on a sample of 82 thyroid test images. The sensitivity and specificity of the abnormality detection were 83% and 64% at the best threshold, respectively. Applying the model on another independent sample of 189 new thyroid images resulted in an AUC of 0.70. CONCLUSION: This study demonstrates the feasibility of using a deep learning-based abnormality detection system to evaluate thyroid cartilage from CT examinations. However, although promising results, the model is not yet able to match an expert's diagnosis.

Tomosynthesis in musculoskeletal pathology.

Tomosynthesis is an imaging technique that uses standard X-ray equipment with digital flat panel detectors to create tomographic images from very low-dose projections obtained at different angles. These images are parallel to the plane of the detector. Filtered back-projection or iterative reconstruction algorithms can be used to produce them. Iterative reconstruction used with a metal artifact reduction algorithm reduces metal artifacts, and therefore, improve image quality and in-depth spatial resolution. The radiation dose is lower compared to that of computed tomography and is two to three times the dose of a standard radiography. Tomosynthesis is intended for the analysis of high-contrast structures and especially for bones. It is superior to projection radiography when bone superimpositions are important or when metal structures hide regions of interest. The high in-plane resolution and its ability to perform exams in weight-bearing positioning are some of the main advantages of this technique. The impossible production of perpendicular multiplanar reconstruction and a limited contrast resolution are its main limitations. Tomosynthesis must be considered as an extension or an addition to standard radiography, as it can be performed in the same diagnostic step. The purpose of this article was to describe the principles, advantages and limitations, and current and future applications in musculoskeletal pathology of tomosynthesis.

[Magnesium sulfate in the prophylaxis of eclampsia: a retrospective study]. / Évaluation de l'utilisation du sulfate de magnésium dans la prévention secondaire de l'éclampsie: étude rétrospective sur 39 cas.

INTRODUCTION: The use of magnesium sulfate (MgSO(4)) has been advocated since 2000 in France in the management of eclampsia. The aim of this study was to determine the frequency of use of this treatment for eclampsia in a French department. PATIENTS AND METHODS: All patients obstetrical patients admitted to Critical Care Units of Seine-Maritime for eclampsia over a period of 7 years (2002-2008) were included. Obstetric data, the treatment used for eclampsia and pre-eclampsia and maternofetal complications were collected. The primary outcome parameter was the use of MgSO(4) in the secondary prevention of eclampsia. RESULTS: Thirty-nine patients were included. Nineteen patients (48%) had eclampsia in prepartum, three (8%) in per-partum and 17 (44%) in post-partum periods. The use of MgSO(4) in the secondary prevention of eclampsia was observed in 92% of cases (36/39). Primary prevention was seen in 8% of cases. The duration of treatment was 2 days (1-7 days). The maternal and perinatal mortality was respectively 2.5 and 11%. CONCLUSION: In this study, the use of MgSO(4) in the secondary prevention is frequent. This result emphasizes the importance of the recommendations of learned societies in the homogenization of the management of rare but serious conditions such as eclampsia.

[Amniotic fluid embolism during curettage for a pregnancy arrest. Case report]. / Embolie amniotique lors d'un curetage pour une grossesse arrêtée. A propos d'un cas.

Amniotic fluid embolism is always a serious complication during the peripartum period. We report the case of an amniotic fluid embolism during curettage for a pregnancy arrest at 13 weeks. The diagnosis was confirmed by the presence of epithelial cells into the maternal blood.

Emerging views on tmRNA-mediated protein tagging and ribosome rescue.

Transfer-messenger RNA (tmRNA), also known as SsrA or 10Sa RNA, is a bacterial ribonucleic acid that recycles 70S ribosomes stalled on problematic messenger RNAs (mRNAs) and also contributes to the degradation of incompletely synthesized peptides. tmRNA acts initially as transfer RNA (tRNA), being aminoacylated at its 3'-end by alanyl-tRNA synthetase, to add alanine to the stalled polypeptide chain. Resumption of translation ensues not on the mRNA on which the ribosomes were stalled but at an internal position in tmRNA. Termination soon occurs, tmRNA recruiting the appropriate termination factors allowing the release of the tagged protein that is subsequently recognized and degraded by specific cytoplasmic and periplasmic proteases, and permits ribosome recycling. Recent data suggest that tmRNA tags bacterial proteins in three other instances; when ribosomes stall at internal sites; during 'readthrough' of canonical termination codons; and when ribosomes are at the termination codon of intact messages. The importance of bacterial tmRNAs for survival, growth under stress, and pathogenesis is also discussed. Recent in vivo and in vitro studies have identified novel ligands of tmRNA. Based on the available experimental evidences, an updated model of tmRNA mediated protein tagging and ribosome rescue in bacteria is presented.

[Limits to arterial embolization treatment of severe postpartum hemorrhage]. / Facteurs d'échec de l'embolisation artérielle dans le traitement des hémorragies graves du post-partum.

OBJECTIVE: To assess the limits of arterial embolization in the management of serious postpartum haemorrhage (PPH). STUDY DESIGN: Retrospective study. PATIENTS AND METHODS: We examined the cases of 29 patients admitted to intensive care units of Rouen University Hospital for PPH between January 1994 and August 1999. Demographic, obstetrical and biological data, the required treatment and eventual side effects were collected and analysed using the appropriate parametric and non parametric tests. RESULTS: Arterial embolization was carried out on 15 patients (52%) with a success rate of 73%. Of the 14 other patients, 11 underwent conservative or radical surgery without further complications, three received medical treatment. No maternal death occurred; however, one patient transferred from a local hospital and already presenting haemodynamic instability suffered cardiac arrest before embolization. Arterial embolization was unsuccessful in four cases, two of which were cases of placenta accreta. These patients were older (p < 0.05) and all had a past history of curettage and/or caesarean section for preceding deliveries (p < 0.01). CONCLUSIONS: Emergency arterial embolization is a valuable therapy in case of PPH but can only be carried out in specialised units. Obstetrical antecedents would appear to constitute a major risk factor and transfer increases the morbidity rate.

Transfer RNA(Ala) recognizes transfer-messenger RNA with specificity; a functional complex prior to entering the ribosome?

tmRNA (SsrA or 10Sa RNA) functions as both a transfer RNA and a messenger RNA, rescues stalled ribosomes and clears the cell of incomplete polypeptides. We report that native Escherichia coli tmRNA interacts specifically with native or synthetic E.coli tRNA alanine (tRNA(Ala)) in vitro, alanine being the first codon of the tmRNA internal open reading frame. Aminoacylatable RNA microhelices also bind tmRNA. Complex formation was monitored by gel retardation assays combined with structural probes. Nucleotides from the acceptor stem of tRNA(Ala) are essential for complex formation with tmRNA. tRNA(Ala) isoacceptors recognize tmRNA with different affinities, with an important contribution from tRNA(Ala) post-transcriptional modifications. The most abundant tRNA(Ala) isoacceptor in vivo binds tmRNA with the highest affinity. A complex between tRNA(Ala) and tmRNA might involve up to 140 tmRNA molecules out of 500 present per E.coli cell. Our data suggest that tmRNA interacts with the tRNA that decodes the resume codon prior to entering the ribosome. Biological implications of promoting specific complexes between tmRNA and aminoacylatable RNAs are discussed, with emphasis on primitive versions of the translation apparatus.

Hepatic expression of SV40 small-T antigen blocks the in vivo CD95-mediated apoptosis.

We have previously demonstrated that CD95-mediated apoptosis of hepatocytes is blocked in a murine model of hepatocarcinogenesis due to the expression of SV40 early sequences encoding the large-T and small-t antigens. In this study, we set out to pinpoint the sequences involved in this apoptosis-resistant phenotype, and tested several mutants of the SV40 early region for their ability to confer protection against CD95-induced apoptosis in transgenic mice. We show that resistance to apoptosis is independent of the transforming character of the mutants and demonstrate that the expression of the small-t antigen alone in transgenic mice is sufficient to confer this resistance. Our data also reveal an increased level of activated Akt kinase in these transgenic mice, and this could account for this hitherto unknown function of the SV40 small-t antigen.

The consequence of p53 overexpression for liver tumor development and the response of transformed murine hepatocytes to genotoxic agents.

To analyse the effect of p53 on liver tumor development, we generated transgenic mice overexpressing wild-type p53 in the liver and crossed them with transgenic mice in which the expression of the SV40 large T antigen (TAg) induces hepatic tumors. Remarkably, whereas preneoplastic TAg liver exhibited anisocaryosis and anisocytosis, TAg/p53 liver never presented any dysplastic cells. Moreover, whereas expression of p53 did not affect hepatic development, its constitutive expression in tumorigenic livers resulted in a significantly enhanced apoptosis once nodules had appeared. In contrast, p53 overexpression did not modify the elevated proliferation of TAg-transformed hepatocytes and had no effect on hepatocarcinoma progression. In vitro analysis of primary hepatocytes exposed to various genotoxic agents showed that p53 failed to sensitize normal or TAg-transformed hepatocytes to apoptosis, except when high doses of doxorubicin, UV-B and UV-C radiation were used. Our results confirmed that the hepatocyte cell type is very resistant to genotoxic agents and showed that constitutive expression of p53 failed to improve their responsiveness. In addition, our results showed that suppression of dysplastic cells, probably by restoring normal cytokinesis and karyokinesis, and enhancement of apoptosis by means of p53 overexpression were insufficient to counteract or delay the TAg-induced liver tumoral progression. Oncogene (2000) 19, 3498 - 3507

Annexin 1 expression and phosphorylation are upregulated during liver regeneration and transformation in antithrombin III SV40 T large antigen transgenic mice.

We have used a transgenic animal model, which constitutively develops hepatocarcinoma (Antithrombin III SV40 T large Antigen: ASV), to study the involvement of Annexin 1 (ANX1) in liver regeneration and malignant transformation. Primary hepatocytes isolated from normal mice did not express ANX1. In contrast, ANX1 was strongly expressed in hepatocytes of transgenic mice during constitutive development of hepatocarcinoma. In ASV transgenic mice, an elevated ANX1 level preceded the appearance of the tumor, indicating that it could be a good marker in the diagnosis of cancer. One-third hepatectomy in normal mice resulted in stimulation of ANX1 synthesis and phosphorylation. This upregulation correlated with increased synthesis of EGF and consequently with increased phosphorylation of the EGF receptor (EGF-R). Stable transfection of a hepatocyte cell line derived from ASV transgenic mice (mhAT2) with antisense complementary DNA for ANX1 reduced the proliferation rate as well as cytosolic phospholipase A(2) (cPLA(2)) activity. Thus, ANX1 expression and phosphorylation could be a factor implicated in liver regeneration and tumorigenesis, either through modulation of cPLA(2) activity or EGF-R function.

Two distinct modes of oncoprotein expression during apoptosis resistance in vincristine and daunorubicin multidrug-resistant HL60 cells.

Apoptosis is a genetically regulated cell death process which results in a variety of morphological changes like chromatin condensation and DNA fragmentation. The decision between survival or death in response to an apoptotic stimulus is determined and regulated in part by oncoproteins which include proteins of the Bcl-2 family (bcl-2, bax, bcl-xL) and bcr-abl. We investigated the effect of these proteins on the induction of this phenomenon in human promyelocytic leukemic HL60 cells and two multidrug resistant homologues selected respectively with vincristine (HL60/VCR) and daunorubicin (HL60R/DNR). We show that sensitive cells at 1 micron and HL60/VCR cells at DNR IC50 were able to undergo apoptosis while HL60R/DNR did not even at much higher concentration of DNR. However, treatment with synthetic C2-ceramide did not sensitize HL60/DNR cells to apoptosis. Cell death through apoptosis or necrosis was accompanied by acidification of the cytosol without mitochondrial membrane depolarization. Western blotting analysis shows that bax is expressed at slightly elevated level in HL60S/VCR in comparison with the other cells lines. Bcl-2 is overexpressed in HL60/VCR but not in HL60R/DNR. However, this cell line displayed a higher expression of bcl-xL. Interestingly, bcr-abl, a dysregulated tyrosine kinase was detected only in HL60R/DNR cells. DNR at the IC50, has no effect on expression of the oncoproteins. These data suggest that in addition of the multidrug resistance phenotype, bcr-abl translocation and bcl-xL overexpression could also account for the development of resistance to cell death induced by anthracyclines in leukemic cells.

Evidence of the role of protein kinase C during aclacinomycin induction of erythroid differentiation in K562 cells.

At subtoxic concentrations, aclacinomycin is effective in controlling erythroid differentiation of K562, a human erythroleukemic cell line. To better understand early events implicated in this process, we have used bisindolylmaleimide (GF109203X), an inhibitor with a high selectivity for protein kinase C (PKC). Our data show that GF109203X inhibits aclacinomycin effects on K562, evidenced by a strong reduction of hemoglobinized cells and a marked decrease of mRNA rates of erythroid genes. To establish firmly PKC involvement, we also verified that aclacinomycin stimulates its rapid translocation, from the cytosolic to the membrane compartment. By Western blot analysis, we also show that after short induction times, PKCalpha was the most implicated.

[Differentiating the activity of anticancer drugs: the role of transcription factors]. / Activité différenciante des médicaments anticancéreux: rôle des facteurs de transcription.

The understanding of the mechanisms responsible for the emergence and evolution of cancers has been in constant progress due to advances in molecular biology. Today it allows to conceive therapeutic alternatives to conventional cytotoxic chemotherapy. Among these, differentiation strategy, which aims at reinducing tumour cells towards a normal phenotype, has known a first clinical application with the use of retinoic acid in acute promyelocytic leukemias. Anthracyclines, traditionally employed in cytotoxic chemotherapy, present also a high potential of differentiation. Their mode of action takes place via the activation of transcription factors, which are proteins that are able to modulate the expression of genes by fixing to regulatory sequences of DNA. These observations therefore allow us to foresee a new pharmacology based on transcription factors for the treatment of cancers.

Piperazine derivatives of butyric acid as differentiating agents in human leukemic cells.

Butyric acid is a potent antineoplastic agent with a well-documented differentiation activity on a wide variety of tumor cells. However, its clinical development is strongly limited by its very short metabolic half-life. In this study we report on the in vitro effects of new original piperazine derivatives of butyric acid on the induction of differentiation and the growth inhibition of human erythroleukemia K562 cells and myeloid leukemia HL60 cells. 1-(2-hydroxyethyl) 4-(1-oxobutyl)-piperazine (HEPB) and [1-(2-hydroxyethyl) 4-(1-oxobutyl)-piperazine] butyrate (HEPDB) were efficient in acting on the differentiation and proliferation of both cell lines, whereas 1-phenyl 4-(1-oxobutyl)-piperazine (PPB) and 1-(3,4-methylene dioxybenzyl) 4-(1-oxobutyl)-piperazine (POB) acted only on proliferation rates. Such derivatives did not induce significant toxicity in mice. These preliminary results should enable, by the development of new series of piperazine derivatives, a better understanding of the mechanisms of action of butyric acid and its analogues on the coupling of growth and differentiation of neoplastic cells.

Automatic time delay optimization between the pump and seed pulses of a broadly tunable femtosecond optical parametric amplifier.

We propose a scheme for optimizing the time delay between the pump and seed pulses of an optical parametric amplifier (OPA) over a large spectral range. The efficiency of this method is demonstrated for a femtosecond BBO parametric amplifier seeded with a white-light continuum pulse. The error signal used for intensity stabilization results from a modulation of the temporal delay between the pump and the continuum pulses and phase-sensitive detection of the amplified signal. It allows us to lock the delay to the position that maximizes the OPA gain.

Anthracyclines as tumor cell differentiating agents: effects on the regulation of erythroid gene expression.

Tumor cells, and particularly leukemic cells, can be considered as maturation-arrested cells which have escaped some normal control and continue to proliferate. This maturation arrest can be reversed by differentiation agents such as antitumor drugs currently used in conventional cytotoxic chemotherapy. In this respect, anthracyclines have been shown to trigger the differentiation of leukemic and solid tumor cells, but the molecular mechanisms by which such drugs lead to the differentiating phenotype are still poorly understood. Using human leukemic multipotent K562 cells, we have demonstrated that subtoxic concentrations of aclacinomycin (ACLA) and doxorubicin (DOX) preferentially stimulate the hemoglobinic pathway (globins and heme synthesis) and the expression of mRNAs of globins and of porphobilinogen deaminase (PBGD). However, our results indicate that both drugs exert this differentiating effect along distinct regulatory pathways. Indeed, only ACLA and not DOX induces the expression of erythropoietin receptor (EpoR) mRNAs and of membrane EpoR, as well as an overexpression of the erythroid transcription factors GATA-1 and NF-E2 known to play a central role in erythroid gene regulation. Similarly, using transfection assays, ACLA but not DOX activates the regulatory regions (promoters and enhancers) of GATA-1, EpoR, PBGD, epsilon- and gamma-globin genes. Finally, results of run-on assays indicate that ACLA induces an enhancement of the transcription rate of these erythroid genes whereas DOX preferentially increases stability of GATA-1, NF-E2 and PBGD mRNAs. In conclusion, ACLA mainly acts at the transcriptional level via specific activation of erythroid regulatory regions whereas DOX rather acts at the posttranscriptional level by increasing the half-lives of erythroid mRNAs.