CT-guided cervical foraminal injection: Is a direct foraminal approach still necessary?

Purpose: Cervical foraminal injection performed with a direct foraminal approach may induce serious neurologic complications. We describe a technique of CT-guided cervical facet joint (CFJ) injection as an indirect foraminal injection, including feasibility and diffusion pathways of the contrast agent. Methods and materials: Retrospective study included 84 punctures in 65 consecutive patients presenting neck pain and/or radiculopathy related to osteoarthritis or soft disc herniation. CT images were obtained from C2 to T1 in supine position, with a metallic landmark on the skin. CFJ punctures were performed by MSK senior radiologists with a lateral approach. CT control of the CFJ opacification was performed after injections of contrast agent (1 ml), followed by slow-acting corticosteroid (25 mg). CFJ opacification was considered as successful when joint space and/or capsular recess opacification occurred. The diffusion of contrast agent in foraminal and epidural spaces was recorded. We assessed the epidural diffusion both on axial and sagittal images, with a classification in two groups (small diffusion or large diffusion). Results: CFJ opacification was successful in 82% (69/84). An epidural and/or foraminal opacification was obtained in 74% (51/69). A foraminal opacification occurred in 92% (47/51) and an epidural opacification in 63% (32/51), with small diffusion in 47% (15/32) and large diffusion in 53% (17/32). No complication occurred. Conclusion: CT- guided CFJ injection is easy to perform and safe. It is most often successful, with a frequent epidural and/or foraminal diffusion of the contrast agent. This technique could be an interesting and safe alternative to foraminal cervical injection.

No implication of thromboxane-prostanoid receptors in reactive hyperemia of skin skeletal muscle in human forearm

L'hyperhémie réactive, définie comme l'augmentation transitoire du flux sanguin après une courte période d'ischémie, pourrait être influencée par des vasoconstricteurs de la famille des prostanoïdes, telle que la thromboxane. Le terutroban (S18886) est un antagoniste spécifique des récepteurs à la thromboxane. L'étude présentée a cherché à déterminer l'effet du terutroban sur l'hyperhémie réactive dans la peau et le muscle squelettique de l'avant-bras de volontaires sains. Vingt volontaires sains ont été randomisés en aveugle pour recevoir oralement 30mg/j de terutroban ou un placebo pendant 5 jours puis réciproquement pendant une deuxième période de 5 jours, selon un schéma cross-over. L'ischémie transitoire a été provoquée par l'occlusion de l'artère brachiale par une manchette gonflée au dessus de la pression systolique. L'hyperhémie réactive était évaluée dans les tissus de l'avant- bras, en mesurant le flux sanguin, pour la peau par une méthode laser Doppler, et pour le muscle au moyen d'une pléthysmographie par jauge de contrainte durant une occlusion veineuse. Au premier et au dernier jour de chaque période de traitement, l'hyperhémie réactive était mesurée avant et 2 heures après l'ingestion du comprimé. Que ce soit dans la peau ou le muscle, le terutroban n'a pas montré d'effet sur le flux de pic post-occlusion ni sur la réponse globale d'hyperhémie, exprimée en aire sous la courbe. En conclusion, dans la peau et le muscle de sujets sains, l'hypérémie réactive n'est pas influencée par les récepteurs spécifiques à la thromboxane.

Artificial muscle for end-stage heart failure.

We describe a device made of artificial muscle for the treatment of end-stage heart failure as an alternative to current heart assist devices. The key component is a matrix of nitinol wires and aramidic fibers called Biometal muscle (BM). When heated electrically, it produces a motorless, smooth, and lifelike motion. The BM is connected to a carbon fiber scaffold, tightening the heart and providing simultaneous assistance to the left and right ventricles. A pacemaker-like microprocessor drives the contraction of the BM. We tested the device in a dedicated bench model of diseased heart. It generated a systolic pressure of 75 mm Hg and ejected a maximum of 330 ml/min, with an ejection fraction of 12%. The device required a power supply of 6 V, 250 mA. This could be the beginning of an era in which BMs integrate or replace the mechanical function of natural muscles.

Plasmid electrotransfer of eye ciliary muscle: principles and therapeutic efficacy using hTNF-alpha soluble receptor in uveitis.

Due to its small size and particular isolating barriers, the eye is an ideal target for local therapy. Recombinant protein ocular delivery requires invasive and painful repeated injections. Alternatively, a transfected tissue might be used as a local producer of transgene-encoded therapeutic protein. We have developed a nondamaging electrically mediated plasmid delivery technique (electrotransfer) targeted to the ciliary muscle, which is used as a reservoir tissue for the long-lasting expression and secretion of therapeutic proteins. High and long-lasting reporter gene expression was observed, which was restricted to the ciliary muscle. Chimeric TNF-alpha soluble receptor (hTNFR-Is) electrotransfer led to elevated protein secretion in aqueous humor and to drastic inhibition of clinical and histological inflammation scores in rats with endotoxin-induced uveitis. No hTNFR-Is was detected in the serum, demonstrating the local delivery of proteins using this method. Plasmid electrotransfer to the ciliary muscle, as performed in this study, did not induce any ocular pathology or structural damage. Local and sustained therapeutic protein production through ciliary muscle electrotransfer is a promising alternative to repeated intraocular protein administration for a large number of inflammatory, degenerative, or angiogenic diseases.

Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation.

The role of Notch signaling in growth/differentiation control of mammalian epithelial cells is still poorly defined. We show that keratinocyte-specific deletion of the Notch1 gene results in marked epidermal hyperplasia and deregulated expression of multiple differentiation markers. In differentiating primary keratinocytes in vitro endogenous Notch1 is required for induction of p21WAF1/Cip1 expression, and activated Notch1 causes growth suppression by inducing p21WAF1/Cip1 expression. Activated Notch1 also induces expression of 'early' differentiation markers, while suppressing the late markers. Induction of p21WAF1/Cip1 expression and early differentiation markers occur through two different mechanisms. The RBP-Jkappa protein binds directly to the endogenous p21 promoter and p21 expression is induced specifically by activated Notch1 through RBP-Jkappa-dependent transcription. Expression of early differentiation markers is RBP-Jkappa-independent and can be induced by both activated Notch1 and Notch2, as well as the highly conserved ankyrin repeat domain of the Notch1 cytoplasmic region. Thus, Notch signaling triggers two distinct pathways leading to keratinocyte growth arrest and differentiation.

Photodynamic Diagnosis of Non-muscle-invasive Bladder Cancer with Hexaminolevulinate Cystoscopy: A Meta-analysis of Detection and Recurrence Based on Raw Data.

BACKGROUND: Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence. OBJECTIVE: To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence. DESIGN, SETTING, AND PARTICIPANTS: This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non-muscle-invasive bladder cancer (NMIBC). INTERVENTION: A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We studied the detection of NMIBC (intention to treat [ITT]: n=831; six studies) and recurrence (per protocol: n=634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection. RESULTS AND LIMITATIONS: BL cystoscopy detected significantly more Ta tumours (14.7%; p<0.001; odds ratio [OR]: 4.898; 95% CI, 1.937-12.390) and CIS lesions (40.8%; p<0.001; OR: 12.372; 95% CI, 6.343-24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p<0.001), significant also in patients with primary (20.7%; p<0.001) and recurrent cancer (27.7%; p<0.001), and in patients at high risk (27.0%; p<0.001) and intermediate risk (35.7%; p=0.004). In 26.7% of patients, CIS was detected only by BL (p<0.001) and was also significant in patients with primary (28.0%; p<0.001) and recurrent cancer (25.0%; p<0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p=0.006; RR: 0.761 [0.627-0.924]), and lower in patients with T1 or CIS (p=0.052; RR: 0.696 [0.482-1.003]), Ta (p=0.040; RR: 0.804 [0.653-0.991]), and in high-risk (p=0.050) and low-risk (p=0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used. CONCLUSIONS: This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9-12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.

The effect of muscle fatigue on stimulus intensity requirements for central and peripheral fatigue quantification.

PURPOSE: The present study was designed to determine the stimulation intensity necessary for an adequate assessment of central and peripheral components of neuromuscular fatigue of the knee extensors. METHODS: Three different stimulation intensities (100, 120 and 150 % of the lowest intensity evoking a plateau in M-waves and twitch amplitudes, optimal stimulation intensity, OSI) were used to assess voluntary activation level (VAL) as well as M-wave, twitch and doublet amplitudes before, during and after an incremental isometric exercise performed by 14 (8 men) healthy and physically active volunteers. A visual analog scale was used to evaluate the associated discomfort. RESULTS: There was no difference (p > 0.05) in VAL between the three intensities before and after exercise. However, we found that stimulating at 100 % OSI may overestimate the extent of peripheral fatigue during exercise, whereas 150 % OSI stimulations led to greater discomfort associated with doublet stimulations as well as to an increased antagonist co-activation compared to 100 % OSI. CONCLUSION: We recommend using 120 % OSI, as it constitutes a good trade-off between discomfort and reliable measurements.

In vivo gene transfer into the ocular ciliary muscle mediated by ultrasound and microbubbles.

This study aimed to assess application of ultrasound (US) combined with microbubbles (MB) to transfect the ciliary muscle of rat eyes. Reporter DNA plasmids encoding for Gaussia luciferase, β-galactosidase or the green fluorescent protein (GFP), alone or mixed with 50% Artison MB, were injected into the ciliary muscle, with or without US exposure (US set at 1 MHz, 2 W/cm(2), 50% duty cycle for 2 min). Luciferase activity was measured in ocular fluids at 7 and 30 days after sonoporation. At 1 week, the US+MB treatment showed a significant increase in luminescence compared with control eyes, injected with plasmid only, with or without MB (×2.6), and, reporter proteins were localized in the ciliary muscle by histochemical analysis. At 1 month, a significant decrease in luciferase activity was observed in all groups. A rise in lens and ciliary muscle temperature was measured during the procedure but did not result in any observable or microscopic damages at 1 and 8 days. The feasibility to transfer gene into the ciliary muscle by US and MB suggests that sonoporation may allow intraocular production of proteins for the treatment of inflammatory, angiogenic and/or degenerative retinal diseases.

Mediastinal reinforcement after induction therapy and pneumonectomy: comparison of intercostal muscle versus diaphragm flaps.

OBJECTIVE: Prospective non-randomised comparison of full-thickness pedicled diaphragm flap with intercostal muscle flap in terms of morbidity and efficiency for bronchial stump coverage after induction therapy followed by pneumonectomy for non-small cell lung cancer (NSCLC). METHODS: Between 1996 and 1998, a consecutive series of 26 patients underwent pneumonectomy following induction therapy. Half of the patients underwent mediastinal reinforcement by use of a pedicled intercostal muscle flap (IF) and half of the patients by use of a pedicled full-thickness diaphragm muscle flap (DF). Patients in both groups were matched according to age, gender, side of pneumonectomy and stage of NSCLC. Postoperative morbidity and mortality were recorded. Six months follow-up including physical examination and pulmonary function testing was performed to examine the incidence of bronchial stump fistulae, gastro-esophageal disorders or chest wall complaints. RESULTS: There was no 30-day mortality in both groups. Complications were observed in one of 13 patients after IF and five of 13 after DF including pneumonia in two (one IF and one DF), visceral herniations in three (DF) and bronchopleural fistula in one patient (DF). There were no symptoms of gastro-esophageal reflux disease (GERD). Postoperative pulmonary function testing revealed no significant differences between the two groups. CONCLUSIONS: Pedicled intercostal and diaphragmatic muscle flaps are both valuable and effective tools for prophylactic mediastinal reinforcement following induction therapy and pneumonectomy. In our series of patients, IF seemed to be associated with a smaller operation-related morbidity than DF, although the difference was not significant. Pedicled full-thickness diaphragmatic flaps may be indicated after induction therapy and extended pneumonectomy with pericardial resection in order to cover the stump and close the pericardial defect since they do not adversely influence pulmonary function.

Atrovastatin-loaded hydrogel affects the smooth muscle cells of human veins

Les pontages veineux restent actuellement un traitement de choix dans les pathologies vasculaires occlusives. Cependant, plusieurs problèmes sont liés à ce type de revascularisation. Premièrement, l'hyperplasie intimale (HI) qui cause une resténose dans 20 à 50% des pontages, conduisant à un échec de la revascularisation. Ce processus est dû à la prolifération et à la migration des cellules musculaires lisses vasculaires vers l'intima, ainsi qu'à une sécrétion de protéines de la matrice extracellulaire conduisant à un épaississement de l'intima, principalement au niveau des anastomoses. Deuxièmement, bien qu'il existe des substances connues pour inhiber l'HI, leur administration systémique répétée est associée à une augmentation de leurs effets secondaires. Aucun dispositif ne permet actuellement la libération d'une telle substance localement au site d'une anastomose vasculaire. Nous avons donc développé un hydrogel d'acide hyaluronique compatible avec une application locale au niveau des anastomoses vasculaires et pouvant être chargé en atorvastatine (ATV) (inhibiteur de la 3-hydroxy-3-methylglutaryl-CoA réductase), substance connue pour inhiber l'HI, dans le but de diminuer le fléau de la resténose. Nous avons tout d'abord testé l'effet de ce gel chargé en ATV sur la prolifération, la migration et la transmigration de cellules musculaires lisses primaires en culture provenant de veines saphènes humaines. Ensuite, nous avons étudié son effet sur différents gènes impliqués dans l'HI. Ceci a permis de montrer que l'ATV diminue la prolifération, la migration et la transmigration des cellules musculaires lisses humaines de façon similaire qu'elle soit ajoutée directement au milieu de culture ou qu'elle soit libérée par l'hydrogel chargé. De même, l'ATV régule de manière simultanée mais différentielle les gènes, en interférant avec le développement de l'HI. Nos expériences montrent que l'HI peut être diminuée in vitro grâce à cet hydrogel d'acide hyaluronique chargé en ATV. Ceci ouvre la porte au développement de futur dispositif permettant de relâcher des substances antisténotiques de façon continue, sur une durée prolongée, et in vivo.

PGC-1α induces mitochondrial and myokine transcriptional programs and lipid droplet and glycogen accumulation in cultured human skeletal muscle cells

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) is a chief activator of mitochondrial and metabolic programs and protects against atrophy in skeletal muscle (skm). Here we tested whether PGC-1α overexpression could restructure the transcriptome and metabolism of primary cultured human skm cells, which display a phenotype that resembles the atrophic phenotype. An oligonucleotide microarray analysis was used to reveal the effects of PGC-1α on the whole transcriptome. Fifty-three different genes showed altered expression in response to PGC-1α: 42 upregulated and 11 downregulated. The main gene ontologies (GO) associated with the upregulated genes were mitochondrial components and processes and this was linked with an increase in COX activity, an indicator of mitochondrial content. Furthermore, PGC-1α enhanced mitochondrial oxidation of palmitate and lactate to CO2, but not glucose oxidation. The other most significantly associated GOs for the upregulated genes were chemotaxis and cytokine activity, and several cytokines, including IL-8/CXCL8, CXCL6, CCL5 and CCL8, were within the most highly induced genes. Indeed, PGC-1α highly increased IL-8 cell protein content. The most upregulated gene was PVALB, which is related to calcium signaling. Potential metabolic regulators of fatty acid and glucose storage were among mainly regulated genes. The mRNA and protein level of FITM1/FIT1, which enhances the formation of lipid droplets, was raised by PGC-1α, while in oleate-incubated cells PGC-1α increased the number of smaller lipid droplets and modestly triglyceride levels, compared to controls. CALM1, the calcium-modulated δ subunit of phosphorylase kinase, was downregulated by PGC-1α, while glycogen phosphorylase was inactivated and glycogen storage was increased by PGC-1α. In conclusion, of the metabolic transcriptome deficiencies of cultured skm cells, PGC-1α rescued the expression of genes encoding mitochondrial proteins and FITM1. Several myokine genes, including IL-8 and CCL5, which are known to be constitutively expressed in human skm cells, were induced by PGC-1α.

Direct three-dimensional myocardial strain tensor quantification and tracking using zHARP.

Images of myocardial strain can be used to diagnose heart disease, plan and monitor treatment, and to learn about cardiac structure and function. Three-dimensional (3D) strain is typically quantified using many magnetic resonance (MR) images obtained in two or three orthogonal planes. Problems with this approach include long scan times, image misregistration, and through-plane motion. This article presents a novel method for calculating cardiac 3D strain using a stack of two or more images acquired in only one orientation. The zHARP pulse sequence encodes in-plane motion using MR tagging and out-of-plane motion using phase encoding, and has been previously shown to be capable of computing 3D displacement within a single image plane. Here, data from two adjacent image planes are combined to yield a 3D strain tensor at each pixel; stacks of zHARP images can be used to derive stacked arrays of 3D strain tensors without imaging multiple orientations and without numerical interpolation. The performance and accuracy of the method is demonstrated in vitro on a phantom and in vivo in four healthy adult human subjects.

Prothèse totale de la hanche par voie antérieure "mini-invasive" [Total hip arthroplasty through anterior "minimal invasive" approach].

Total hip replacement has seen a tremendous development and has become one of the most successful surgical interventions in orthopaedics. While during the first decades of development of total hip arthroplasty the fixation of the implant into the bone was the main concern, the focus has shifted towards surgical technique and soft tissue handling. In order to avoid permanent soft tissue damage, muscular dysfunction and concerns in regards to cosmetics, minimal invasive and anatomic approaches have been developed. We here provide a short overview on various methods of total hip replacements and we describe our technique through a minimal invasive direct anterior approach. While muscle and nerve damage is minimal, this technique allows for a rapid rehabilitation and is associated with an excellent functional outcome and a minimal risk for dislocation.

BCL9 is an essential component of canonical Wnt signaling that mediates the differentiation of myogenic progenitors during muscle regeneration.

Muscle stem cells and their progeny play a fundamental role in the regeneration of adult skeletal muscle. We have previously shown that activation of the canonical Wnt/beta-catenin signaling pathway in adult myogenic progenitors is required for their transition from rapidly dividing transient amplifying cells to more differentiated progenitors. Whereas Wnt signaling in Drosophila is dependent on the presence of the co-regulator Legless, previous studies of the mammalian ortholog of Legless, BCL9 (and its homolog, BCL9-2), have not revealed an essential role of these proteins in Wnt signaling in specific tissues during development. Using Cre-lox technology to delete BCL9 and BCL9-2 in the myogenic lineage in vivo and RNAi technology to knockdown the protein levels in vitro, we show that BCL9 is required for activation of the Wnt/beta-catenin cascade in adult mammalian myogenic progenitors. We observed that the nuclear localization of beta-catenin and downstream TCF/LEF-mediated transcription, which are normally observed in myogenic progenitors upon addition of exogenous Wnt and during muscle regeneration, were abrogated when BCL9/9-2 levels were reduced. Furthermore, reductions of BCL9/9-2 inhibited the promotion of myogenic differentiation by Wnt and the normal regenerative response of skeletal muscle. These results suggest a critical role of BCL9/9-2 in the Wnt-mediated regulation of adult, as opposed to embryonic, myogenic progenitors.