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Large skeletal defects of the upper extremity pose a serious clinical problem with potentially deleterious effects on both function and viability of the limb. Recent advances in the microsurgical techniques involved in free vascularized bone transfers for complex limb injuries have dramatically improved limb salvage and musculoskeletal reconstruction. This study evaluates the clinical and radiographic results of 18 patients who underwent reconstruction of large defects of the long bones of the upper extremity with free vascularized fibular bone grafts. Mean patient age was 27 years (7−43 years) and mean follow-up was 4 years (1−10 years). The results confirm the value of vascularized fibular grafts for bridging large bone defects in the upper extremity. © 2011 Wiley-Liss, Inc. Microsurgery 2011.

Massive bony defects of the lower extremity are usually the result of high-energy trauma, tumor resection, or severe sepsis. Vascularized fibular grafts are useful in the reconstruction of large skeletal defects, especially in cases of scarred and avascular recipient sites, or in patients with combined bone and soft-tissue defects. Microvascular free fibula transfer is considered the most suitable autograft for reconstruction of the middle tibia because of its long cylindrical straight shape, mechanical strength, predictable vascular pedicle, and hypertrophy potential. The ability to fold the free fibula into two segments or to combine it with massive allografts is a useful technique for reconstruction of massive bone defects of the femur or proximal tibia. It can also be transferred with skin, fascia, or muscle as a composite flap. Proximal epiphyseal fibula transfer has the potential for longitudinal growth and can be used in the hip joint remodeling procedures. Complications can be minimized by careful preoperative planning of the procedure, meticulous intraoperative microsurgical techniques, and strict postoperative rehabilitation protocols. This literature review highlights the different surgical techniques, indications, results, factors influencing the outcome, and major complications of free vascularized fibular graft for management of skeletal or composite defects of the lower limb.

Congenital deficiency of the thumb greatly compromises hand function, because the normal thumb contributes at least 40% of its usefulness. The method of choice in the treatment of this functional liability is the pollicization of the index finger. This study presents the long term outcome of 21 index finger pollicizations in 18 patients, with a mean follow-up time of 9 years. The thumb deficiency was bilateral in 3 patients, whereas in 7 it was associated with radial club hand. The result was considered excellent in 75%, good in 19%, and poor in 6% of the 21 pollicizations, according to Percival's scoring system. The less rewarding function was obtained in the presence of associated radial club hand in combination with late reconstruction. Index finger pollicization is the method of choice in the treatment of thumb aplasia or severe hypoplasia. The younger patients adapt easier and use the new thumb in a more natural way.

Purpose To examine the afferent pathways of the scapholunate interosseous ligament (SLIL)–generated stimuli and their contribution to the overall carpal proprioception. Methods We examined 5 selected patients with preganglionic global root avulsion, confirmed by previous brachial plexus exploration, during the initial stage of carpal arthrodesis surgery. Despite their anesthetic-flail extremity, both the distal axon and the ganglionic cell were intact and able to transfer afferent stimuli. We placed electrodes subcutaneously over the adjacent areas of the ulnar, median, and radial nerves at the elbow region and performed an intraoperative neurophysiologic study. We studied the homologous sensory action potentials (SAPs) generated at the wrist in relaxation, flexion, extension, radial deviation, and ulnar deviation positions at each nerve and repeated them in 2 stages. The first took place with the SLIL intact and the second with the SLIL lacerated. The noise from the rest of the wrist elements was digitally eliminated. Results After the SLIL laceration, SAP intensities recorded at the median nerve in every wrist position were reduced. The radial and ulnar nerves showed differences of lesser degrees between the recorded SAP intensities before and after the ligament sectioning in every carpal position, with only the radial nerve following a specific pattern. The SAP intensity recorded at the median nerve in every carpal motion after the SLIL laceration was similar to the SAP intensity at relaxation with the SLIL intact, whereas recordings of various intensities were present for the radial and ulnar nerves. Conclusions The SLIL generates proprioceptive stimuli at every wrist position. The main innervation of the whole SLIL derives from the anterior interosseous nerve; a partial contribution of the posterior interosseous nerve focused on the dorsal subregion of the ligament may also be present.

Objectives:We investigated proinflammatory M1 and immunomodulatory M2 activation profiles of circulating monocytes in relapsing experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, and tested whether altered M1/M2 equilibrium promotes CNS inflammation. Results:Approaches of MRI macrophage tracking with USPIO nanoparticles and expression patterns of M1/M2 macrophages and microglia in brain and M1/M2 monocytes in blood samples at various disease stages revealed that M1/M2 equilibrium in blood and CNS favors mild EAE, while imbalance towards M1 promotes relapsing EAE. We consequently investigated whether M2 activated monocyte restoration in peripheral blood could cure acute clinical EAE disease. Administration of ex vivo activated M2 monocytes both suppressed ongoing severe EAE and increased immunomodulatory expression pattern in lesions, confirming their role in the induction of recovery. Conclusion:We conclude that imbalance of monocyte activation profiles and impaired M2 expression, are key factors in development of relapses. Our study opens new perspectives for therapeutic applications in MS.

Only 18 cases of congenital radial pseudarthrosis have been reported in the English literature; of these, 4 have been treated with free vascularized fibular graft. We present a case of a 9-year-old female patient with neurofibromatosis type 1 who underwent gradual distraction through the pseudarthrosis site and subsequent vascularized fibular grafting for isolated congenital pseudarthrosis of her left radius and concomitant longitudinal and angular deformity of the wrist joint. At the last follow-up, 10 years postoperatively, the patient has maintained bony union, with full wrist flexion-extension and forearm pronation-supination.

Carpal tunnel syndrome (CTS) is a well-known clinical entity. Release of the transverse carpal ligament is considered to be the treatment of choice. Both open and endoscopic release of the transverse carpal ligament in CTS has yielded satisfactory results. Although these procedures are very common in surgical practice, inadequate release and intraoperative damage to neural elements are very frustrating complication for both the patient and the surgeon. The purpose of this study was to demonstrate incidental intraoperative findings of variations of the standard median nerve anatomy. We obtained incidental intraoperative identification of median nerve variations in 110 consecutive patients operated with open release of the transverse carpal ligament in CTS. Using the Amadio classification, we found intraoperatively variations of median nerve at the wrist in 11 patients. In three patients, there was an aberrant sensory branch arising from the ulnar side of the median nerve and piercing the ulnar margin of the transverse carpal ligament. Neural variations arising from the ulnar aspect of the median nerve were common and could be a cause of iatrogenic injury during endoscopic or open release. Surgeons should be aware of anomalous branches, which should be recognized and separately decompressed if needed. Clin. Anat. 21:514–518, 2008. © 2008 Wiley-Liss, Inc.

E B 3 is a specification language for information systems. The core of the E B 3 language consists of process algebraic specifications describing the behaviour of the entities in a system, and attribute function definitions describing the entity attributes. The verification of E B 3 specifications against temporal properties is of great interest to users of E B 3 . In this paper, we propose a translation from E B 3 to LOTOS NT (LNT for short), a value-passing concurrent language with classical process algebra features. Our translation ensures the one-to-one correspondence between states and transitions of the labelled transition systems corresponding to the E B 3 and LNT specifications. We automated this translation with the E B 3 2 L N T tool, thus equipping the E B 3 method with the functional verification features available in the CADP toolbox.

A 17-yr-old male patient was admitted with a transverse sharp transection caused by broken glass at the volar aspect of his left wrist. Clinical examination showed loss of sensation at the distribution of the median nerve to the thumb, index, and middle finger and an inability to flex the middle finger. Under regional anesthesia and a high humerus tourniquet, surgical exploration of the wound with binocular loupe magnification showed a bifid median nerve with a persistent thin median artery running between the two nerve trunks. The bifid median nerve was sharply and transversely transected, slightly proximal to the transverse carpal ligament. The palmaris longus tendon and the flexor digitorum superficialis tendon of the middle finger were also cut. The flexor digitorum tendon was sutured with a two-strand technique augmented with a running epitendinous suture. The two trunks of the bifid median nerve were repaired separately using microsurgical technique and 8-0 nylon epineural sutures. Postoperatively, the hand was immobilized in a palmar short-arm splint that was removed at 40 d. A progressive Tinel sign was evident 30 d postoperatively. At 3 mo, the patient experienced light touch sensation at the tip of the index and middle fingers. At the last follow-up, 2.5 yr after his injury, the patient has complete nerve functional recovery without atrophy of the thenar muscles and with strong thumb opposition. © 2016 by Begell House, Inc.

Background The optimum fixation device for the critical size bone defect is not established yet. Objective A reliable, feasible and low-cost fixation device for the long-term maintenance of a critical bone defect. Methods A custom-made plate made of poly-methyl-methacrylate was used for the fixation of a critical defect of rats' femurs. The screws were securely fixing both on the plate and the bone. A three point bending test, aimed to resemble the in vivo loading pattern, a Finite Element Analysis and a 24-week in vivo monitoring of the integrity of the plate fixation were utilized. Results The plate has linear and reproducible behavior. It presents no discontinuities in the stress field of the fixation. Its properties are attributed to the material and the locking principle. It fails beyond the level of magnitude of the normal ambulatory loads. In vivo, 100% of the plates maintained the bone defect intact up to 12 weeks and 85% of them at 24 weeks. Conclusion This novel locking plate shows optimal biomechanical performance and reliability with high long-term in vivo survival rate. It is fully implantable, inexpensive and easily manufactured. It can be qualified for long term critical defect fixation in bone regeneration studies.

In photonic crystals (PCs), strong scattering and destructive wave interference lead to a modification of the photon density of states in particular energy regions and along certain crystallographic directions1,2. The consequences of this range from suppression and enhancement of luminescence3,4,5,6,7 to narrow-band bright reflections useful for colour sensors8,9, displays10 and tuneable filters11,12,13,14. Here we demonstrate large-area films of porous elastomeric photonic crystals (EPCs) that are compressively–decompressively cycled to reversibly shift the position of the photonic band structure over a large wavelength range. Owing to their low compressive threshold, such porous EPCs can be used for imaging that is pressure and time sensitive, for example, to obtain colour fingerprints with high accuracy. Furthermore, by incorporating luminescent PbS quantum dots in the EPCs, the photonic stop-gap can be tuned through the near-infrared (NIR) quantum dot photoluminescence (PL) peak. Thereby we demonstrate a tuneable modification of photonic characteristics, including the suppression and enhancement in emission and dynamic modification of luminescence lifetimes.

The varying degrees of spontaneous reinnervation that occur in untreated obstetrical brachial plexus palsy leave characteristic deformities of the shoulder, elbow, forearm, wrist, and hand. Common sequelae are internal rotation and adduction deformity of the shoulder, elbow flexion contractures, forearm supination deformity, and lack of wrist extension and finger flexion. Early microsurgical reconstruction of the affected plexus leads to a more rewarding overall function of the upper arm, but residual deformities might appear later which are similar, although less serious, than those observed in untreated cases. Secondary procedures of the shoulder, elbow, forearm, and hand will improve the appearance and function of the upper extremity in late cases of obstetrical brachial plexus. Careful preoperative planning is mandatory and a multistage approach should be applied, depending on the type of palsy and the age of the patient.

The brachial plexus is a complex network of nerves which extends from the neck to the axilla and which supplies motor, sensory, and sympathetic fibers to the upper extremity. Generally it is formed by the union of the ventral primary rami of the spinal nerves, C5-C8 and T1, the so-called "roots" of the brachial plexus. The goal here is to examine the neural architecture of the brachial plexus. The most constant arrangement of nerve fibers will be delineated, and then the predominant variations in neural architecture will be defined, particularly the prefixed and postfixed plexus, as well as the microanatomy and anatomy of the major terminal branches of the plexus. Multiple tracts connect many parts of the nervous system, and multiple ascending and descending tracts connect the peripheral nervous system (PNS) and lower spinal centers with the brain. This reflects that the nervous system is able to extract different pieces of sensory information from its surroundings and encode them separately, and that it is able to control specific aspects of motor behavior using different sets of neurons. Examination of the major sensory or motor pathways reveals a highly and tightly organized nervous system. In particular, at each of many levels, we see fairly exact maps of the world within the brain. In an effort to understand the functional neuroanatomy of the brachial plexus, this paper will focus briefly on the nervous connections of the nerves of the upper extremity with the brain. The goal here is to better understand "what the brain sees" after nerve injury and repair.

The purpose of this study was to assess the maximum rapid intraoperative elongation of the rat sciatic nerve with the use of tissue expander, and its possible functional recovery. One hundred and eight rats were divided into five groups, and their right sciatic nerves were expanded with a 10-cc, 12-cc, 14-cc, 16-cc, and 18-cc expander, respectively, for 1 h. The functional recovery of the nerve was assessed at intervals up to 3 months, using the sciatic function index (SFI), neurophysiological indices, and histology. The maximum intraoperative elongation was observed in group IV (16-cc volume of tissue expander), at about 23.83%. SFI decreased between the first and seventh postoperative days, but gradually recovered, reaching preoperative values in all groups according to the formulas of De Medinaceli et al. (Exp. Neurol. 77:634-643, 1982) and Bain et al. (Plast. Reconstr. Surg. 83:129-136, 1989). Latency and motor conduction velocity demonstrated deterioration after expansion, which peaked after surgery. Recovery was gradually completed by the end of the experiment. The histological findings indicated minor aberrations immediately after expansion and maximal demyelination with axonal disruption on day 15. The reparative process started by day 30 and continued until day 90, when almost no histological changes were observed. In conclusion, intraoperative nerve expansion successfully elongates the rat sciatic nerve up to 23.83%. But it causes functional and morphological abnormalities, which are of moderate to severe degree, are of short duration, and are reversible. Intraoperative nerve expansion might be a valuable solution in the treatment of short nerve gaps, but its clinical application still needs to be evaluated. Microsurgery

The aim of this study was to assess the effectiveness of reinnervation using end-to-side neurorrhaphy in the upper extremity of the rabbit. The cut right ulnar nerve was repaired and sutured to the side of the median nerve about 3 cm above the elbow joint. The extent of reinnervation was quantitatively evaluated, as well as the integrity of the intact donor nerve in 36 rabbits randomly treated with fresh or delayed nerve repair with or without perineurotomy. Evaluations included nerve conduction velocity (NCV) of both the ulnar and medial nerves, dry muscle weight, and histologic examination (neurofilament stain and morphometric assessment) at 3 and 6 months postoperatively. NCV recovery rates were 79% and 87% for the ulnar nerve, and 89% and 94% for the median nerve compared to contralateral intact nerves, at 3 and 6 months, respectively. Flexor carpi ulnaris muscle mass measurements revealed a recovery in dry muscle weight of about 81% and 88% at 3 and 6 months, respectively, compared to the intact contralateral flexor carpi ulnaris. Histologic studies with neurofilament staining reveal numerous axonal sprouts at the distal end of the median nerve, indicative of myelinated axonal regeneration. Morphometric analysis demonstrated no difference between fresh and delayed repairs. These results indicate that in the upper extremity of rabbits, end-to-side neurorrhaphy permits axonal regeneration from the intact donor nerve, and is associated with satisfactory recovery. The effect of the procedure on the donor nerve was negligible.

In the past, the attitude toward surgical repair of sciatic and peroneal nerve lesions was excessively pessimistic. Refinements of microsurgical technique, nerve conduction studies, and the establishment of indications and optimal timings for surgical interventions have led to significant improvements in outcomes, making repair worthwhile in most cases. Tendon transfers can augment functional outcomes, and are performed as secondary procedures or (in selected cases) in combination with the initial repair. Developments in the basic sciences, bioengineering, and medical imaging may further improve the results of management of these serious nerve injuries.

This study was designed to quantitatively assess long-term end-to-side neurorrhaphy in rabbits. The cut right ulnar nerve was repaired and sutured to the median nerve, in which a perineurial window was created in an end-to-side fashion 3 cm above the elbow joint. Both the extent of the reinnervation and the integrity of the intact donor nerve were evaluated in 36 rabbits randomly treated with fresh or delayed nerve repair. Evaluations included motor nerve conduction velocity (MNCV), dry muscle weight (DMW), and histological examinations at 9 and 12 months postoperatively. The recovery rates of MNCV were 90.1% and 92.8% for the ulnar nerve, and 95.7% and 96.8% for the median nerve, compared to intact contralateral nerves at 9 and 12 months, respectively. MNCV was not detectable for the ulnar nerve in control animals, while it was normal for the median nerve. Recoveries of flexor carpi ulnaris dry muscle weight of about 90.7% and 94.5% were observed at 9 and 12 months postoperatively, respectively. However, muscle mass measurements revealed a recovery of only 31.3% and 27% for control groups at 9 and 12 months postoperatively. The differences between experimental groups and control groups were statistically significant (P < 0.01). Neurofilament and silver stains showed numerous sprouting axons originating from the median nerve to the ulnar nerve. The results indicate that end-to-side neurorrhaphy could induce axonal sprouting from the main nerve trunk of upper limbs in rabbits, leading to useful functional recovery.

A summary approach in the determination of eigenvalues and eigenvectors of transport of information fields in 2-port cell networks, is presented. The dispersion relation whose nodes constitute the eigenvalues is formed as a sum of diagrams which topologically are mapped 1-1 to the graphs of our paper. We find the matrix representation of these graphs, as an Abelian semigroup of the Boolean matrices formed by all the possible graphs of this kind. We also find the algebra that distinguishes the class of these matrices from the rest of the general Boolean matrices. Generalization of these symmetry properties for n-port cell finite networks is currently being investigated. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Two-stage flexor tendon reconstruction (Hunter) is indicated in children with extensive adhesions in zone 2 of the hand, with some reservations concerning the patient's age and cooperation. Nine children (mean age 6.9 years) were treated with the modified Paneva-Holevich technique, which has advantages over the classic Hunter reconstructions. It involves an intrasynovial graft (FDS of the injured finger) that is anatomically stable and morphologically more appropriate compared with free grafts. The size of the silicone rod is precisely assessed in the first stage, the proximal tenorrhaphy has healed by the time the second stage is performed, and donor site morbidity is minimized. After a mean follow-up of 40.1 months, the mean total active motion was 196 degrees, and eight patients achieved a good or excellent result according to the Buck-Gramcko and the revised Strickland scale. Staged flexor tendon reconstruction is technically feasible even in very young children. Results in children are comparable to those achieved in adults.

Obstetrical brachial plexus palsy invariably involves the upper roots. The natural history of the injury shows that if the condition is left untreated, spontaneous reinnervation that occurs in a variable degree in these patients leaves characteristic deformities of the shoulder and elbow. Common sequelae are the internal rotation and adduction deformity of the shoulder, and elbow flexion contractures. Early microsurgical reconstruction of the affected plexus leads to more rewarding overall function of the shoulder and elbow, but residual deformities might appear again, similar to the ones noticed in untreated cases, that are even less serious. Thus, secondary procedures are mandatory to reanimating the shoulder and elbow, and especially to provide adequate abduction and external rotation of the shoulder and a more neutral appearance of the elbow regarding flexion–extension equilibrium.

Gene expression profiling of tumors allows the establishment of relationships between gene expression profiles and sensitivity to anticancer drugs. In an attempt to study the molecular determinants of the activity of platinum compounds, we explored the publicly available databases of the National Cancer Institute (NCI; http://dtp.nci.nih.gov), which allow access to the gene expression profiles of the 60 cell lines for which drug cytotoxicity patterns already existed. Using this database, we have conducted an in silico research to identify the genes the expression of which was positively or negatively correlated to the sensitivity to four platinum compounds (cisplatin, carboplatin, oxaliplatin and tetraplatin). Important similarities were noticed between cisplatin and carboplatin on one hand, and tetraplatin and oxaliplatin on the other hand. In the restricted panel of 1416 genes and molecular markers, we identified 204 markers, among which 120 corresponded to identified genes, that significantly correlated (P < 0.001) with the cytotoxicity of at least one platinum compound. For example, the functionality of the p53-activated pathway appeared positively correlated with the cytotoxicity of all platinum compounds. More specific are the positive correlations between RAS gene mutations and MYC expression and the cellular sensitivity to oxaliplatin. Among the parameters already known as related to the sensitivity to platinum compounds, we identified, in the complete set of 9400 genes, numerous significant relationships, such as the negative correlations between ERB-B2 and BCL-XL expressions and the cytotoxicity of the platinum compounds. Public databases mining, therefore, appears to be a valuable tool for the identification of determinants of anticancer drug activity in tumors.

Background Among the techniques used to induce and control gene expression, a non-invasive, physical approach based on local heat in combination with a heat-sensitive promoter represents a promising alternative but requires accurate temperature control in vivo. MRI-guided focused ultrasound (MRI-FUS) with real-time feedback control allows automatic execution of a predefined temperature-time trajectory. The purpose of this study was to demonstrate temporal and spatial control of transgene expression based on a well-defined local hyperthermia generated by MRI-FUS. Methods Expression of the green fluorescent protein (GFP) marker gene was used. Two cell lines were derived from C6 glioma cells. The GFP expression of the first one is under the control of the CMV promoter, whereas it is under the control of the HSP70 promoter in the second one and thus inducible by heat. Subcutaneous tumours were generated by injection in immuno-deficient mice and rats. Tumours were subjected to temperatures varying from 42 to 50 °C for 3 to 25 min controlled by MRI-FUS and analyzed 24 h after the heat-shock. Endogenous HSP70 expression and C6 cell distribution were also analyzed. Results The results demonstrate strong expression at 50 °C applied during a short time period (3 min) without affecting cell viability. Induced expression was also clearly shown for temperature in the range 44–48 °C but not at 42 °C. Conclusions Heating with MRI-FUS allows a tight and non-invasive control of transgene expression in a tumour. Copyright © 2002 John Wiley & Sons, Ltd.

Titre de la communication : Enrichment of an in vivo phage display repertoire by subtraction for the easy identification of biomarkers of pathology. Vargas-Sanchez J.K., Vekris A., Mordelet E., Dubourdieu-Cassagno N., Ottones F., Petry K.G and Boiziau C. INSERM U1049, Bordeaux University, Neuroinflammation, Imaging and Therapy of Multiple Sclerosis, 146 rue Leo Saignat, 33 076 Bordeaux cedex, France. Abstract Aim. To develop a method that enriches, after in vivo phage display selection, the repertoire with clones specific for a pathological state. Materials and Methods. In a neuroinflammation model, we performed a subtraction based on DNA hybridization and restriction enzyme digestion of the common clones recovered from the central nervous system (CNS) of healthy and experimental autoimmune encephalomyelitis (EAE) rats. The subtraction efficiency was monitored by massive sequencing and clones were examined for binding specificity onto EAE CNS rat tissues and human blood brain barrier cells (hCMEC/D3) under inflammatory conditions. Results. 95% of the clones common to EAE and HEALTHY repertoires were subtracted, allowing clone enrichment. Conclusion. This physical subtraction discarded from a complex repertoire the non-specific selected ligands. STRATEGY 1) Three rounds of in vivo phage peptide selection in EAE female Lewis rats ("EAE repertoire") vs controls ("HEALTHY repertoire"). 2) DNA subtraction of the most common sequences between «HEALTHY» and «EAE» phage repertoires to obtain a third EAE specific «SUBTRACTION » phage repertoire. 3) Massive sequencing of the three repertoires and bioinformatic analysis to identify the peptides sequences with high EAE specificity. 4) Biological tests of potential EAE specific phage clones with CNS tissues from EAE and Healthy control rats. 5) Biological tests of the EAE specific peptide and phage clones on the BBB in vitro model (hCMEC/D3 cells) under inflammatory conditions (IL-1β stimulation). 6) Target separation and identification by cross-link between the selected phage clones and hMEC/D3 endothelial cells targets under IL-1β stimulation vs controls.

Purpose: The aim of the present study was to present the long-term radiographic results with distraction osteogenesis in traumatic or congenital length discrepancies of long bones of the hand. Methods: The medical records and radiographs of 65 consecutive patients (27 metacarpals and 55 phalanges) with either traumatic or congenital digital length discrepancies were retrospectively reviewed. The mean follow-up was 8.2 years. The mean distraction period was 21 days with a distraction rate of 4 × 0.25 mm/day. Callus consolidation was obtained in all patients. Results: The bones were lengthened by a mean amount of 17.5 mm, with a mean increase in bone length of 68 ± 17.3%. The mean healing index was 28.57 days/cm. Ray reconstruction with callus distraction can be applied effectively in skeletally immature or mature patients with congenital differences of the hand or amputated fingers. Conclusion: A distraction rate of 1 mm/day proved to be a safe rate of lengthening in both metacarpals and phalanges. © 2015 Elsevier Ltd. All rights reserved.

EB-3 is a specification language for information systems. The core of the EB-3 language consists of process algebraic specifications describing the behaviour of entities in a system, and attribute functions that are recursive functions evaluated on the system execution trace describing entity attributes. The verification ofEB-3 specifications against temporal properties is of great interest to users of EB-3. In this thesis, we focus on liveness properties of information systems, which express the eventuality that certain actions take place. The verification of liveness properties can beachieved with model checking. First, we present an operational semantics for EB-3 programs, in which attribute functions are computed during program evolution and their values are stored into program memory. This semantics permits us to define an automatic translation from EB-3 to LNT, a value-passing concurrent language with classical process algebra features. Our translation ensures the one-to-one correspondence between states and transitions of the labelled transition systems corresponding to theEB-3 and LNT specifications. Then, we automate this translation with the EB-3toLNT tool, thus equipping the EB-3 method with the functional verification features available in the model checking toolbox CADP. With the aim of improving the model checking results of this approach, we explore abstraction techniques for information systems specified inEB-3. In particular, we concentrate on a specific family of systems called parametric, whose behaviour is scaled in keeping with the predefined value of a system parameter. Finally, we apply this method on the EB-3 context, EB-3 est un langage de spécification développé pour la spécification des systèmes d'information. Le noyau du langage EB-3comprend des spécifications d'algèbre de processus afin de décrire le comportement des entités du système et des fonctions d'attributs qui sont des fonctions récursives dont l'évaluation se fait sur la trace d'exécution du système décrivant les attributs des entités. La vérification de propriétés temporelles en EB-3 est un sujet de grande importance pour des utilisateurs de EB-3. Dans cette thèse, on se focalise sur les propriétés de vivacité concernant des systèmes d'information exprimant l'éventualité que certaines actions puissent s'exécuter. La vérification des propriétés de vivacité se fait à l'aide de model checking. Dans un premier temps, on présente une sémantique opérationnelle deEB-3, selon laquelle les fonctions d'attributs sont évaluées pendant l'exécution du programme puis stockées. Cette sémantique nous permet de définir une traduction automatique de EB-3 vers LNT, qui est un langage simultané enrichi d'une algèbre de processus. Notre traduction assure la correspondance un à un entre les états et les transitions des systèmes étiquetés de transition correspondent respectivement à des spécifications EB-3 et LNT. Ensuite, on automatise la traduction grâce à l'outil EB3toLNT fournissant aux utilisateurs de EB-3 une tous les outils de vérification fonctionnelle disponible dans CADP. Dans le but d'améliorer les résultats de notre approche concernant le model checking, on explore des techniques d'abstraction dédiées aux systèmes d'information spécifiées en EB-3. En particulier, on se focalise sur une famille spécifique de systèmes qui s'appellent paramétriques dont le comportement varie en fonction de la valeur prédéfinie d'un paramètre du système. Enfin, on applique cette méthode dans le contexte de EB-3

SUMMARY: Reconstruction of elbow function in severe or late brachial plexus injuries represents a challenge to the reconstructive microsurgeons. The current sophisticated techniques of nerve reconstruction in combination with secondary local or free functional muscle transfers, may offer satisfactory outcome. Latissimus dorsi can be transferred as a pedicled or free muscle to restore elbow function. We present our experience with elbow reanimation in late cases of brachial plexus paralysis utilising latissimus dorsi muscle transfer. From 1998 to 2006 we operated 103 patients with brachial plexus paralysis. Amongst these patients, 21 were late cases and underwent latissimus dorsi muscle transfer for elbow reanimation. Ten patients had free latissimus dorsi transfer for elbow flexion. Free latissimus dorsi muscle was neurotised either directly via three intercostals in three patients or with a nerve transfer procedure using the contralateral seventh cervical nerve root in seven patients. Care was taken to maintain the proper tension to the muscle, which must hold the elbow in static flexion of about 120 degrees at the end of the procedure. Powerful elbow flexion (M4-M4+) or extension (M4) was obtained after the first 3 months in all patients who had an ipsilateral pedicled latissimus dorsi transfer. In the group of free muscle transfers, elbow flexion was seen after 6-8 months. After the initiation of muscle contraction, eight of the patients regained elbow flexion of M3-M4+. Latissimus dorsi muscle transfer is a reliable method for elbow reanimation. Appropriate postoperative management is also an important factor to obtain better outcome. Injury-International Journal of the Care of the Injured

Birth brachial plexus injury usually affects the upper roots. In most cases, spontaneous reinnervation occurs in a variable degree. This aberrant reinnervation leaves characteristic deformities of the shoulder, elbow, forearm, wrist, and hand. Common sequelae are the internal rotation and adduction deformity of the shoulder, elbow flexion contractures, forearm supination deformity, and lack of wrist extension and finger flexion. Nowadays, the strategy in the management of obstetrical brachial plexus palsy focuses in close follow-up of the baby up to 3-6 months and if there are no signs of recovery, microsurgical repair is indicated. Nonetheless, palliative surgery consisting of an ensemble of secondary procedures is used to further improve the overall function of the upper extremity in patients who present late or fail to improve after primary management. These secondary procedures include transfers of free vascularized and neurotized muscles. We present and discuss our experience in treating early and/or late obstetrical palsies utilizing the above-mentioned microsurgical strategy and review the literature on the management of brachial plexus birth palsy. Microsurgery

Background Local production of therapeutic proteins, e.g. for cancer treatments, is based on gene therapy approaches and requires tight spatial and temporal control of gene expression. Here we demonstrate the use of local hyperthermia of varying intensity and duration to control the expression of a transgene under control of the thermoinducible hsp70 (heat shock protein) promoter. Methods Heat-induced expression of the EGFP (green fluorescent protein) reporter gene was characterized using a stably transfected glioma C6 cell line expressing the EGFP gene under control of the heat inducible minimal hsp70 promoter both in vitro and in vivo for subcutaneous tumors in immunodeficient mice. Results A heat shock of 20–30 min at 43°C in cell culture led to a maximum EGFP concentration at about 24 h. Heat treatments at higher temperature (up to 48°C) but with shorter durations (down to 30 s) also induced strong EGFP expression. Local heating in situ led to gradients in EGFP expression which decreased with increasing distance from the heat source. Conclusion Local hyperthermia, in combination with a heat sensitive promoter, represents a method for the spatial and temporal control of transgene expression. Copyright © 2000 John Wiley & Sons, Ltd.

Brachial plexus injuries may result in devastating paralysis, especially if they involve all the roots. The upper roots are often traumatized, and therefore elbow flexion is usually lost. The prognosis of these injuries is grave if root avulsions are present and the paralysis includes the hand as well. The current management of brachial plexus injuries should be early, aggressive microsurgical reconstruction of the plexus, combining various neurotizations with intraplexus and extraplexus nerve donors. Following this principle, we present the results of musculocutaneous neurotization in our unit, as well as a review of the literature on this subject. Our results are comparable to those reported in the literature, and indicate that the strongest function is achieved after neurotization via intraplexus donors, while some extraplexus donors (i.e., phrenic and accessory nerve) can offer equally strong elbow flexion, especially if they are used in combination. Neurotization of the musculocutaneous nerve should be one of the primary goals in the reconstruction of the injured plexus, since the return of elbow flexion is of paramount importance in daily activity. The restoration of function is ensured if the stronger and healthier motor donors are dedicated to the neurotization of the musculocutaneous nerve. Sometimes in order to match the axonal number of the target to the lower number of axons offered by the donors, two or more donor nerves may be driven to the same target, such as the musculocutaneous nerve.

Brachial plexus injuries may result in devastating paralysis, especially if they involve all the roots. The upper roots are often traumatized, and therefore elbow flexion is usually lost. The prognosis of these injuries is grave if root avulsions are present and the paralysis includes the hand as well. The current management of brachial plexus injuries should be early, aggressive microsurgical reconstruction of the plexus, combining various neurotizations with intraplexus and extraplexus nerve donors. Following this principle, we present the results of musculocutaneous neurotization in our unit, as well as a review of the literature on this subject. Our results are comparable to those reported in the literature, and indicate that the strongest function is achieved after neurotization via intraplexus donors, while some extraplexus donors (i.e., phrenic and accessory nerve) can offer equally strong elbow flexion, especially if they are used in combination. Neurotization of the musculocutaneous nerve should be one of the primary goals in the reconstruction of the injured plexus, since the return of elbow flexion is of paramount importance in daily activity. The restoration of function is ensured if the stronger and healthier motor donors are dedicated to the neurotization of the musculocutaneous nerve. Sometimes in order to match the axonal number of the target to the lower number of axons offered by the donors, two or more donor nerves may be driven to the same target, such as the musculocutaneous nerve. Microsurgery

The evolution of microsurgery popularized the free functioning muscle transfers as secondary procedures to reanimate paralyzed extremities after severance of the brachial plexus, especially when the surgeon deals with late cases. Studies considering transplantation, describe thrombophilic factors as a cause of severe complications after transplantation, such as acute or early rejection episodes, delayed graft function, or chronic graft dysfunction. It is the first time that thrombophilia associated with free muscle-graft rejection is reported. A young man who had two free functional muscle transfers for brachial plexus reconstruction in the same forearm within an interval of 6 months. The free functional muscle transfer was failed in both cases because of vein thrombosis and subsequent arterial clot. The possibility of thrombophilia was investigated and during the genetic investigation it was discovered that he was heterozygous for the mutations of factor V, G1691A-Leiden, A4070G and homozygous for the MTHFR C677T mutation.

1. Anastasios Vekris, MD 2. Dimitra Zafeiratou, MD 3. Antonia Andriopoulou 4. Amalia Tsiatoura (dzafeiratou{at}gmail.com) 1. Athens, Greece Alopecia areata (AA) is a chronic, autoimmune disease that causes inflammation of hair follicles. AA may lead to non-scarring hair loss that can

Distraction osteogenesis is the current method of choice for bone lengthening. Despite the gain in experience, various complications are reported, among them, adverse effects on peripheral-nerve function. In order to thoroughly investigate the effect of distraction on neural tissue, a distraction osteogenesis model in the rat was established, using the femur of 30 Sprague-Dawley rats. The animals were randomized in three groups, following different rates of distraction (0.5 mm, 1.0 mm, and 1.5 mm/day) for 50, 25, and 16 days, respectively, so that the final length of distraction was the same in all groups. The mean sciatic function index ranged near normal in all groups. All groups demonstrated decrease of conduction velocity and the area under the curve of the compound action potential, while morphologic alterations consisted of decrease in the number of axons and evidence of active degeneration. Animals in Groups 1 (0.5 mm/day) and 2 (1 mm/day) displayed comparable changes, while in Group 3 animals (1.5 mm/day), changes were significantly more adversely dramatic. The safest and fastest rate of distraction in this rat model was determined to be 1 mm/day.

EB-3 is a specification language for information systems. The core of the EB-3 language consists of process algebraic specifications describing the behaviour of entities in a system, and attribute functions that are recursive functions evaluated on the system execution trace describing entity attributes. The verification ofEB-3 specifications against temporal properties is of great interest to users of EB-3. In this thesis, we focus on liveness properties of information systems, which express the eventuality that certain actions take place. The verification of liveness properties can beachieved with model checking. First, we present an operational semantics for EB-3 programs, in which attribute functions are computed during program evolution and their values are stored into program memory. This semantics permits us to define an automatic translation from EB-3 to LNT, a value-passing concurrent language with classical process algebra features. Our translation ensures the one-to-one correspondence between states and transitions of the labelled transition systems corresponding to theEB-3 and LNT specifications. Then, we automate this translation with the EB-3toLNT tool, thus equipping the EB-3 method with the functional verification features available in the model checking toolbox CADP. With the aim of improving the model checking results of this approach, we explore abstraction techniques for information systems specified inEB-3. In particular, we concentrate on a specific family of systems called parametric, whose behaviour is scaled in keeping with the predefined value of a system parameter. Finally, we apply this method on the EB-3 context, EB-3 est un langage de spécification développé pour la spécification des systèmes d'information. Le noyau du langage EB-3comprend des spécifications d'algèbre de processus afin de décrire le comportement des entités du système et des fonctions d'attributs qui sont des fonctions récursives dont l'évaluation se fait sur la trace d'exécution du système décrivant les attributs des entités. La vérification de propriétés temporelles en EB-3 est un sujet de grande importance pour des utilisateurs de EB-3. Dans cette thèse, on se focalise sur les propriétés de vivacité concernant des systèmes d'information exprimant l'éventualité que certaines actions puissent s'exécuter. La vérification des propriétés de vivacité se fait à l'aide de model checking. Dans un premier temps, on présente une sémantique opérationnelle deEB-3, selon laquelle les fonctions d'attributs sont évaluées pendant l'exécution du programme puis stockées. Cette sémantique nous permet de définir une traduction automatique de EB-3 vers LNT, qui est un langage simultané enrichi d'une algèbre de processus. Notre traduction assure la correspondance un à un entre les états et les transitions des systèmes étiquetés de transition correspondent respectivement à des spécifications EB-3 et LNT. Ensuite, on automatise la traduction grâce à l'outil EB3toLNT fournissant aux utilisateurs de EB-3 une tous les outils de vérification fonctionnelle disponible dans CADP. Dans le but d'améliorer les résultats de notre approche concernant le model checking, on explore des techniques d'abstraction dédiées aux systèmes d'information spécifiées en EB-3. En particulier, on se focalise sur une famille spécifique de systèmes qui s'appellent paramétriques dont le comportement varie en fonction de la valeur prédéfinie d'un paramètre du système. Enfin, on applique cette méthode dans le contexte de EB-3